Sample records for retina therapy srt

  1. Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model

    Seifert, Eric; Roh, Young-Jung; Fritz, Andreas; Park, Young Gun; Kang, Seungbum; Theisen-Kunde, Dirk; Brinkmann, Ralf


    Selective Retina Therapy (SRT) targets the Retinal Pigment Epithelium (RPE) without effecting neighboring layers as the photoreceptors or the choroid. SRT related RPE defects are ophthalmoscopically invisible. Owing to this invisibility and the variation of the threshold radiant exposure for RPE damage the treating physician does not know whether the treatment was successful or not. Thus measurement techniques enabling a correct dosing are a demanded element in SRT devices. The acquired signal can be used for monitoring or automatic irradiation control. Existing monitoring techniques are based on the detection of micro-bubbles. These bubbles are the origin of RPE cell damage for pulse durations in the ns and μs time regime 5μs. The detection can be performed by optical or acoustical approaches. Monitoring based on an acoustical approach has already been used to study the beneficial effects of SRT on diabetic macula edema and central serous retinopathy. We have developed a first real time feedback technique able to detect micro-bubble induced characteristics in the backscattered laser light fast enough to cease the laser irradiation within a burst. Therefore the laser energy within a burst of at most 30 pulses is increased linearly with every pulse. The laser irradiation is ceased as soon as micro-bubbles are detected. With this automatic approach it was possible to observe invisible lesions, an intact photoreceptor layer and a reconstruction of the RPE within one week.

  2. A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation

    Young Gun Park


    Full Text Available Purpose. This study evaluates functional changes in electroretinographic findings after selective retina therapy (SRT compared to panretinal photocoagulation (PRP in rabbits. Methods. The right eyes of 12 Chinchilla rabbits received 200 laser treatment spots. The right eyes of six rabbits received SRT (SRT group, whereas the other six animals were treated using PRP on the right eye (PRP group. The eyes were investigated using full-field ERG 1 hour and 3 weeks after treatment. Histologic exam to assess the tissue response of lasers was performed on 3 weeks. Results. No significant changes in the mean ROD or CR b-wave amplitudes of the SRT lesions were evident, compared to baseline, 1 h after laser treatment (p=0.372 and 0.278, resp.. In addition, the OPs and 30 Hz flickers of the SRT lesions were not significantly altered (p=0.17 and 0.243, resp.. At 3 weeks, similar results were found. Comparing the two groups, the ROD b-wave amplitude was reduced in the PRP and SRT groups to 60.04±4.2% and 92.32±6.43% of baseline (p<0.001. Histologically, there was no visible photoreceptor alterations on week 3. Conclusions. SRT in rabbit eyes induced less functional loss than PRP in both rod-mediated retinal function and cone-mediated retinal function. In addition, SRT irradiated eyes had no functional loss compared to its control.


    Milena Vujanovic


    Full Text Available The therapy of the retina vasculitis is very complex. The basic therapeuticprinciple is to find a balance between the medicament toxicity and the seriousness ofthe retina disease. In easy forms of the disease, with a good seeing sharpness, it issufficient to observe a patient with no therapy at ali. For serious diseases themedicaments to be chosen are corticosteroids. Tf there is no favorable response to thecorticosteroid therapy, in bilateral serious forms of the retina vasculitis and especiallyin the Behchet disease, a therapy with cytostatics is applied. The most frequently usedare cyclophosphamide and chlorambucil. In the last few years s highly-selectiveimmunosuppressive cyclosporine A in small doses is used combined withcorticosteroids. A new approach to suppressing the auto-aggressive Ag-specific Tcellsand their pro-inflammatory products implies the use of a new generation of immunosuppressive medicaments such as tacrolimus (FK 506 and T-cell specificantimetabolites. More recently the desensibilization by the retina S-antigen has beenused in the therapy of the retina vasculitis.

  4. Dynamic trajectory-based couch motion for improvement of radiation therapy trajectories in cranial SRT

    MacDonald, R. Lee [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 4R2 (Canada); Thomas, Christopher G., E-mail: [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 4R2 (Canada); Department of Medical Physics, Nova Scotia Cancer Centre, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V7 (Canada); Department of Radiation Oncology, Dalhousie University, Halifax, Nova Scotia B3H 4R2 (Canada); Department of Radiology, Dalhousie University, Halifax, Nova Scotia B3H 4R2 (Canada)


    Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space, indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors’ study indicated that simultaneous couch and gantry motion

  5. Effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats

    Xiao Liu


    ABSTRACT Objective:To study the effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats.Methods:SD rats were selected as experimental animals and divided into control group, model group and ozone group, and after diabetic models were built, ozone enema was conducted. Retina tissue was collected, TUNEL kits were used to detect the number of apoptotic cells, and Elisa kits were used to detect the contents of nerve damage molecules, angiogenesis-related molecules and endoplasmic reticulum stress molecules. Results:The number of apoptotic cells in retina tissue of model group was significantly more than that of control group, and the number of apoptotic cells in retina tissue of ozone group was significantly less than that of model group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of model group were significantly higher than those of control group, and PEDF content was lower than that of control group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of ozone group were significantly lower than those of model group, and PEDF content was higher than that of model group.Conclusion:Ozone therapy can reduce the number of apoptotic cells while reduce nerve cell injury and inhibit angiogenesis and endoplasmic reticulum stress in retina tissue of diabetic rats.

  6. SRT: design and technical specifications

    Olmi, L.; Grueff, G.

    The Sardinia Radio Telescope (SRT) is a general purpose, fully steerable radio telescope currently being built in Sardinia, that will be operated by the National Institute for Astrophysics (INAF). The SRT will be a large-aperture antenna (64-m diameter) with a classical Gregorian configuration and the possibility to use three different focal positions. The primary and secondary reflectors are shaped to minimize spillover and the standing waves between the feed and the subreflector. The primary active surface will give the SRT the possibility to operate in the 3-mm band, and will thus contribute significantly to many science areas. At present, the foundation of the antenna is almost complete, and the components of the alidade and of the track are under construction.

  7. Stem cell biology and cell transplantation therapy in the retina.

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo


    Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells is an important treatment strategy. Although adult neurogenesis occurs in restricted regions, the CNS has poor potential for regeneration to compensate for cell loss. Thus, cell transplantation into damaged or diseased CNS tissues is a promising approach to treating various neurodegenerative disorders. Transplantation of photoreceptors or retinal pigment epithelium cells derived from human ES cells can restore some visual function. Patient-specific iPS cells may lead to customized cell therapy. However, regeneration of retinal function will require a detailed understanding of eye development, visual system circuitry, and retinal degeneration pathology. Here, we review the current progress in retinal regeneration, focusing on the therapeutic potential of pluripotent stem cells.

  8. Regeneration of the retina: toward stem cell therapy for degenerative retinal diseases.

    Jeon, Sohee; Oh, Il-Hoan


    Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases.

  9. WE-A-19A-01: SRT I: Comparison of SRT Techniques

    Kim, G [UCSD Medical Center, La Jolla, CA (United States); Schlesinger, D [University of Virginia Health Systems, Charlottesville, VA (United States); Descovich, M [University of California San Francisco, San Francisco, CA (United States)


    Within the past several years, the field of radiosurgery has seen numerous technological enhancements, including new dedicated devices for stereotactic delivery, the use of re-locatable frames to facilitate fractionated delivery and the image guided frameless approaches. The goal of this symposium is to compare and contrast competing technologies for cranial SRS/SRT. The symposium will open with a review of the general concept of cranial SRS/SRT procedures as well as describe the key differences from conventional radiotherapy. The speakers will then review each of the delivery technique (Gamma Knife, CyberKnife and Conventional linear accelerator) in turn. The focus of each speaker will be to describe the general workflow of each SRS modality, indications and counterindications for treatment. To compare and contrast different technologies, 2–3 cases examples demonstrating interesting treatment situations and expected outcomes, a sample treatment plan (either live or pre-recorded with live commentary) demonstrating the treatment planning technique, and machine and patient-specific QA required for treatment (if applicable). Additionally, workflows and data describing the use of immobilization devices or tracking/monitoring during SRS/SRT delivery will also be discussed. The session will close with a roundtable discussion of methods to evaluate plan quality, and achievable technical and clinical goals for intracranial SRS. Learning Objectives: Understand the key differences between cranial SRS/SRT and conventional treatments. Review Gamma Knife, CyberKnife and Conventional Linac-based radiosurgery delivery techniques and quality assurance Compare and contrast treatment plans, treatment planning strategy and and quality assurance procedures for each technology. Be able to establish cranial SRS/SRT procedure with optimized quality assurance program for each technology.

  10. Terapia gênica em distrofias hereditárias de retina Gene therapy for inherited retinal dystrophies

    Monique Côco


    Full Text Available As distrofias hereditárias de retina abrangem um amplo número de doenças caracterizadas por lenta e progressiva degeneração da retina. São o resultado de mutações em genes expressos em fotorreceptores e no epitélio pigmentado da retina. A herança pode ser autossômica dominante, autossômica recessiva, ligada ao X recessiva, digênica ou herança mitocondrial. Atualmente não há tratamento para essas doenças e os pacientes convivem com a perda progressiva da visão. O aconselhamento genético e o suporte para reabilitação têm indicação nestes casos. Pesquisas envolvendo a base molecular e genética dessas doenças está continuamente em expansão e ampliam as perspectivas para novas formas de tratamento. Dessa forma, a terapia gênica, que consiste na inserção de material genético exógeno em células de um indivíduo com finalidade terapêutica, tem sido a principal forma de tratamento para as distrofias hereditárias de retina. O olho é um órgão peculiar para a terapia gênica, pois é anatomicamente dividido em compartimentos, imunologicamente privilegiado e com meios transparentes. A maioria das doenças oculares tem defeitos em genes conhecidos. Além disso, há modelo animal bem caracterizado para algumas condições. Propostas para pesquisa clínica em terapia gênica nas degenerações retinianas hereditárias com defeito no gene RPE65, recentemente tiveram aprovação ética e os resultados preliminares obtidos trouxeram grandes expectativas na melhora da qualidade de vida dos pacientes.The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these

  11. Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1

    Khare, B.; Krishnan, V.; Rajashankar, K.R.; I-Hsiu, H.; Xin, M.; Ton-That, H.; Narayana, S.V. (Texas-HSC); (Cornell); (UAB)


    The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2) and three pilins (GBS80, GBS52 and GBS104). Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively. The S. agalactiae housekeeping sortase, SrtA, whose gene is present at a different location and does not catalyze pilus polymerization, was shown to be involved in cell wall anchoring of pilus polymers. To understand the structural basis of sortases involved in such diverse functions, we determined the crystal structures of S. agalactiae SrtC1 and SrtA. Both enzymes are made of an eight-stranded beta-barrel core with variations in their active site architecture. SrtA exhibits a catalytic triad arrangement similar to that in Streptococcus pyogenes SrtA but different from that in Staphylococcus aureus SrtA. In contrast, the SrtC1 enzyme contains an N-terminal helical domain and a 'lid' in its putative active site, which is similar to that seen in Streptococcus pneumoniae pilus-specific sortases, although with subtle differences in positioning and composition. To understand the effect of such differences on substrate recognition, we have also determined the crystal structure of a SrtC1 mutant, in which the conserved DP(W/F/Y) motif was replaced with the sorting signal motif of GBS80, IPNTG. By comparing the structures of WT wild type SrtA and SrtC1 and the 'lid' mutant of SrtC1, we propose that structural elements within the active site and the lid may be important for defining the role of specific sortase in pili biogenesis.

  12. The retina

    van Reyk, David M; Gillies, Mark C; Davies, Michael Jonathan


    of oxidants by vascular endothelium and leukocytes. There is substantial evidence from animal and clinical studies for both impaired antioxidant defences and increased oxidative damage in the retinae of diabetic subjects that have been, in the case of animal studies, reversible with antioxidant......A prominent and early feature of the retinopathy of diabetes mellitus is a diffuse increase in vascular permeability. As the disease develops, the development of frank macular oedema may result in vision loss. That reactive oxygen species production is likely to be elevated in the retina......, and that certain regions of the retina are enriched in substrates for lipid peroxidation, may create an environment susceptible to oxidative damage. This may be more so in the diabetic retina, where hyperglycaemia may lead to elevated oxidant production by a number of mechanisms, including the production...

  13. SRT and SBRT: Current practices for QA dosimetry and 3D

    Benedict, S H; Cai, J; Libby, B; Lovelock, M; Schlesinger, D; Sheng, K; Yang, W, E-mail: SHB4X@hscmail.mcc.virginia.ed


    The major feature that separates stereotactic radiation therapy (cranial SRT) and stereotactic body radiation therapy (SBRT) from conventional radiation treatment is the delivery of large doses in a few fractions which results in a high biological effective dose (BED). In order to minimize the normal tissue toxicity, quality assurance of the conformation of high doses to the target and rapid fall off doses away from the target is critical. The practice of SRT and SBRT therefore requires a high-level of confidence in the accuracy of the entire treatment delivery process. In SRT and SBRT confidence in this accuracy is accomplished by the integration of modern imaging, simulation, treatment planning and delivery technologies into all phases of the treatment process; from treatment simulation and planning and continuing throughout beam delivery. In this report some of the findings of Task group 101 of the AAPM will be presented which outlines the best-practice guidelines for SBRT. The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information in this task group is provided for establishing an SBRT program, including protocols, equipment, resources, and QA procedures.

  14. WE-F-16A-03: 3D Printer Application in Proton Therapy: A Novel Method to Deliver Passive-Scattering Proton Beams with a Fixed Range and Modulation for SRS and SRT

    Ding, X; Witztum, A; Liang, X; Reiche, M; Lin, H; Teo, B; Yin, L; Fiene, J; McDonough, J; Kassaee, A [University Pennsylvania, Philadelphia, PA (United States)


    Purpose: To present a novel technique to deliver passive-scattering proton beam with fixed range and modulation using a 3D printed patient-specific bolus for proton stereotactic radiosurgery and radiotherapy. Methods: A CIRS head phantom was used to simulate a patient with a small brain lesion. A custom bolus was created in the Eclipse Treatment Planning System (TPS) to compensate for the different water equivalent depths from the patient surface to the target from multiple beam directions. To simulate arc therapy, a plan was created on the initial CT using three passive-scattering proton beams with a fixed range and modulations irradiating from different angles. The DICOM-RT structure file of the bolus was exported from the TPS and converted to STL format for 3D printing. The phantom was rescanned with the printed custom bolus and head cup to verify the dose distribution comparing to the initial plan. EBT3 films were placed in the sagital plane of the target to verify the delivered dose distribution. The relative stopping power of the printing material(ABSplus-P430) was measured using the Zebra multi-plate ion chamber. Results: The relative stopping power of the 3D printing material, ABSplus-P430 was 1.05 which is almost water equivalent. The dose difference between verification CT and Initial CT is almost negligible. Film measurement also confirmed the accuracy for this new proton delivery technique. Conclusion: Our method using 3D printed range modifiers simplify the treatment delivery of multiple passive-scattering beams in treatment of small lesion in brain. This technique makes delivery of multiple beam more efficient and can be extended to allow arc therapy with proton beams. The ability to create and construct complex patient specific bolus structures provides a new dimension in creating optimized quality treatment plans not only for proton therapy but also for electron and photon therapy.

  15. Stereotactic radiotherapy (SRT) for acoustic neuroma by linear accelerator

    Sakamoto, Tooru; Shirato, Hiroki; Fukuda, Satoshi [Hokkaido Univ., Sapporo (Japan). School of Medicine] [and others


    We analyzed forty one patients with acoustic neuroma treated by SRT giving 36 Gy in 20 fractions to 48 Gy in 23 fractions during 1991 and 1997, and found a sterilization of tumor size in 97.6%. Twenty-six patients had measurable hearing before and after SRT and 43.5% of patients showed change in pure tone average less than 10 dB, 82.6% less than 20 dB at the last follow-up examination. Facial and trigeminal nerve function was evaluated in 41 patients. Transient facial weakness developed in 4.8% and trigeminal neuropathy in 9.6% of irradiated cases. We consider that SRT complications are less than that of gamma-knife, although the longer follow-up period should be needed. (author)

  16. Helping the Retina Regenerate

    ... Briefs > Helping the retina regenerate Helping the retina regenerate NEI Audacious Goals Initiative report outlines strategies to replace or reprogram neurons in the retina News Brief 03/30/17 ...

  17. Infrared retina

    Krishna, Sanjay; Hayat, Majeed M.; Tyo, J. Scott; Jang, Woo-Yong


    Exemplary embodiments provide an infrared (IR) retinal system and method for making and using the IR retinal system. The IR retinal system can include adaptive sensor elements, whose properties including, e.g., spectral response, signal-to-noise ratio, polarization, or amplitude can be tailored at pixel level by changing the applied bias voltage across the detector. "Color" imagery can be obtained from the IR retinal system by using a single focal plane array. The IR sensor elements can be spectrally, spatially and temporally adaptive using quantum-confined transitions in nanoscale quantum dots. The IR sensor elements can be used as building blocks of an infrared retina, similar to cones of human retina, and can be designed to work in the long-wave infrared portion of the electromagnetic spectrum ranging from about 8 .mu.m to about 12 .mu.m as well as the mid-wave portion ranging from about 3 .mu.m to about 5 .mu.m.

  18. The SRT reconstruction algorithm for semiquantification in PET imaging

    Kastis, George A., E-mail: [Research Center of Mathematics, Academy of Athens, Athens 11527 (Greece); Gaitanis, Anastasios [Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens 11527 (Greece); Samartzis, Alexandros P. [Nuclear Medicine Department, Evangelismos General Hospital, Athens 10676 (Greece); Fokas, Athanasios S. [Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB30WA, United Kingdom and Research Center of Mathematics, Academy of Athens, Athens 11527 (Greece)


    Purpose: The spline reconstruction technique (SRT) is a new, fast algorithm based on a novel numerical implementation of an analytic representation of the inverse Radon transform. The mathematical details of this algorithm and comparisons with filtered backprojection were presented earlier in the literature. In this study, the authors present a comparison between SRT and the ordered-subsets expectation–maximization (OSEM) algorithm for determining contrast and semiquantitative indices of {sup 18}F-FDG uptake. Methods: The authors implemented SRT in the software for tomographic image reconstruction (STIR) open-source platform and evaluated this technique using simulated and real sinograms obtained from the GE Discovery ST positron emission tomography/computer tomography scanner. All simulations and reconstructions were performed in STIR. For OSEM, the authors used the clinical protocol of their scanner, namely, 21 subsets and two iterations. The authors also examined images at one, four, six, and ten iterations. For the simulation studies, the authors analyzed an image-quality phantom with cold and hot lesions. Two different versions of the phantom were employed at two different hot-sphere lesion-to-background ratios (LBRs), namely, 2:1 and 4:1. For each noiseless sinogram, 20 Poisson realizations were created at five different noise levels. In addition to making visual comparisons of the reconstructed images, the authors determined contrast and bias as a function of the background image roughness (IR). For the real-data studies, sinograms of an image-quality phantom simulating the human torso were employed. The authors determined contrast and LBR as a function of the background IR. Finally, the authors present plots of contrast as a function of IR after smoothing each reconstructed image with Gaussian filters of six different sizes. Statistical significance was determined by employing the Wilcoxon rank-sum test. Results: In both simulated and real studies, SRT

  19. Implementation and Analysis of Interval SRT Radix-2 Division Algorithm

    Milind R. Patel


    Full Text Available Interval arithmetic gives computation for closed bound set of real numbers which provides two values for single result. It gives confirmation that the error which exists due to the mathematical computation does not exceed over defined accuracy. Interval arithmetic provides higher precision and accuracy than the floating point arithmetic. Software computation for interval arithmetic is quite slow. Hardware implementation of the interval arithmetic provides considerable improvement in speed with respect to its software approach. We have used floating point hardware for interval arithmetic to improve the speed of computation. We present the implementation and analysis of interval radix-2 SRT division algorithm in double precision. SRT division gives faster response when partial remainder is relatively small in computation.

  20. Progress Towards AIRS Science Team Version-7 at SRT

    Susskind, Joel; Blaisdell, John; Iredell, Lena; Kouvaris, Louis


    The AIRS Science Team Version-6 retrieval algorithm is currently producing level-3 Climate Data Records (CDRs) from AIRS that have been proven useful to scientists in understanding climate processes. CDRs are gridded level-3 products which include all cases passing AIRS Climate QC. SRT has made significant further improvements to AIRS Version-6. At the last Science Team Meeting, we described results using SRT AIRS Version-6.22. SRT Version-6.22 is now an official build at JPL called 6.2.4. Version-6.22 results are significantly improved compared to Version-6, especially with regard to water vapor and ozone profiles. We have adapted AIRS Version-6.22 to run with CrIS/ATMS, at the Sounder SIPS which processed CrIS/ATMS data for August 2014. JPL AIRS Version-6.22 uses the Version-6 AIRS tuning coefficients. AIRS Version-6.22 has at least two limitations which must be improved before finalization of Version-7: Version-6.22 total O3 has spurious high values in the presence of Saharan dust over the ocean; and Version-6.22 retrieved upper stratospheric temperatures are very poor in polar winter. SRT Version-6.28 addresses the first concern. John Blaisdell ran the analog of AIRS Version-6.28 in his own sandbox at JPL for the 14th and 15th of every month in 2014 and all of July and October for 2014. AIRS Version-6.28a is hot off the presses and addresses the second concern.

  1. Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

    Krema, Hatem, E-mail: [Department of Ocular Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Heydarian, Mostafa [Department of Radiation Medicine, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Beiki-Ardakani, Akbar [Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Weisbrod, Daniel [Department of Ocular Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Xu, Wei [Department of Biostatistics, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Laperriere, Normand J.; Sahgal, Arjun [Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada)


    Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

  2. How to improve the High Frequency capabilities of SRT

    Pisanu, T.; Morsiani, M.; Pernechele, C.; Buffa, F.; Vargiu, G.

    The SRT (Sardinia Radio Telescope) is a general purpose, fully steerable, active surface equipped, 64 meters antenna, which is in an advanced construction state near Cagliari (Sardinia - Italy). It will be an antenna which could improve a lot the performances of the EVN network, particularly at frequencies higher than 22 GHz. The main antenna geometry consist of a shaped reflector system pair, based on the classical parabola-ellipse Gregorian configuration. It is designed to be able to operate with a good efficiency in a frequency range from 300 MHz up to 100 GHz. This frequency range, is divided in two parts which define also two antenna operational modes, one up to 22 GHz with a minimal amount of accessory instrumentation, and the other up to 100 GHz with a full complement of instrumentation. The goal is to make it possible to build a telescope operable up to 22 GHz, and then upgrade it at a future date to operate at frequencies up to 100 GHz. In order to get these goals, the SRT Metrology group is studying and developing different types of strategies, instrumentation, and techniques for measuring and reducing the various components of pointing and efficiency errors, taking advantage also from experiences developed in other radio telescopes, like GBT (Green Bank Telescope, USA), LMT (Large Millimiter Telescope, MEX), and IRAM (Institut de Radio Astronomie Millimetrique, Fr). Many of those system will be installed and tested at the 32 meters radio-telescope in Medicina (Bologna), before of their implementation on SRT. (astro-ph/0412692)

  3. Theoretical and practical aspects relating to the photothermal therapy of tumors of the retina and choroid: A review.

    Niederer, P; Fankhauser, F


    Photothermal treatment of tumors of the retina and choroid such as retinoblastomas, malignant melanomas, benign tumors as well as of vascular malformations can be performed by using laser radiation. A number of basic physical laws have to be taken into account in this procedure. Of particular importance thereby are: Arrhenius' law to approximate the kinetics of protein denaturation and photocoagulation, furthermore the electromagnetic radiation field, the distribution of both radiant and thermal energy induced in tumors and vascular structures, the influence of the wavelength and laser pulse duration (exposure time), as well as of the optical properties of the tissue. Strict confinement of the extent of the photothermal damage is critical since such pathological entities are frequently located close to the macula or optic nerve head.The conditions for tumor destruction are best fulfilled when using radiation in the near-infrared range of the electromagnetic spectrum such as that emitted from the diode (810 nm) and the Nd: YAG (1064 nm) laser, because of the good optical penetration properties of these radiations in tissue. Short wavelength sources of radiation, such as the argon ion (488, 514 nm) or the freqeuency-doubled Nd: YAG (532 nm) laser are less well suited for the irradiation of large vascular structures due to their poor penetration depths. However, for vascular formations with a small thickness (1 mm or less), short wavelength sources appear to be the most appropriate choice. Optical coupling of radiant energy to the eye by means of indirect ophthalmoscopic systems or positive contact lenses is furthermore of importance. Strong positive lenses may lead to severe constrictions of the laser beam within the anterior segment, that leads to high irradiance increasing the probability for structures to be damaged; with negative contact lenses, such as the -64 D Goldmann type lens, this danger is largely absent.

  4. How to improve the High Frequency capabilities of SRT

    Pisanu, T; Pernechele, C; Buffa, F; Vargiu, G


    The SRT (Sardinia Radio Telescope) is a general purpose, fully steerable, active surface equipped, 64 meters antenna, which is in an advanced construction state near Cagliari (Sardinia - Italy). It will be an antenna which could improve a lot the performances of the EVN network, particularly at frequencies higher than 22 GHz. The main antenna geometry consist of a shaped reflector system pair, based on the classical parabola-ellipse Gregorian configuration. It is designed to be able to operate with a good efficiency in a frequency range from 300 MHz up to 100 GHz. This frequency range, is divided in two parts which define also two antenna operational modes, one up to 22 GHz with a minimal amount of accessory instrumentation, and the other up to 100 GHz with a full complement of instrumentation. The goal is to make it possible to build a telescope operable up to 22 GHz, and then upgrade it at a future date to operate at frequencies up to 100 GHz. In order to get these goals, the SRT Metrology group is studying...

  5. Large-scale reconstitution of a retina-to-brain pathway in adult rats using gene therapy and bridging grafts: An anatomical and behavioral analysis.

    You, Si-Wei; Hellström, Mats; Pollett, Margaret A; LeVaillant, Chrisna; Moses, Colette; Rigby, Paul J; Penrose, Marissa; Rodger, Jennifer; Harvey, Alan R


    Peripheral nerve (PN) grafts can be used to bridge tissue defects in the CNS. Using a PN-to-optic nerve (ON) graft model, we combined gene therapy with pharmacotherapy to promote the long-distance regeneration of injured adult retinal ganglion cells (RGCs). Autologous sciatic nerve was sutured onto the transected ON and the distal end immediately inserted into contralateral superior colliculus (SC). Control rats received intraocular injections of saline or adeno-associated virus (AAV) encoding GFP. In experimental groups, three bi-cistronic AAV vectors encoding ciliary neurotrophic factor (CNTF) were injected into different regions of the grafted eye. Each vector encoded a different fluorescent reporter to assess retinotopic order in the regenerate projection. To encourage sprouting/synaptogenesis, after 6 weeks some AAV-CNTF injected rats received an intravitreal injection of recombinant brain-derived neurotrophic factor (rBDNF) or AAV-BDNF. Four months after surgery, cholera toxin B was used to visualize regenerate RGC axons. RGC viability and axonal regrowth into SC were significantly greater in AAV-CNTF groups. In some cases, near the insertion site, regenerate axonal density resembled retinal terminal densities seen in normal SC. Complex arbors were seen in superficial but not deep SC layers and many terminals were immunopositive for presynaptic proteins vGlut2 and SV2. There was improvement in visual function via the grafted eye with significantly greater pupillary constriction in both AAV-CNTF+BDNF groups. In both control and AAV-CNTF+rBDNF groups the extent of light avoidance correlated with the maximal distance of axonal penetration into superficial SC. Despite the robust regrowth of RGC axons back into the SC, axons originating from different parts of the retina were intermixed at the PN graft/host SC interface, indicating that there remained a lack of order in this extensive regenerate projection. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Toward Successful Implementation of Speech Recognition Technology: A Survey of SRT Utilization Issues in Healthcare Settings.

    Clarke, Martina A; King, Joshua L; Kim, Min Soon


    To evaluate physician utilization of speech recognition technology (SRT) for medical documentation in two hospitals. A quantitative survey was used to collect data in the areas of practice, electronic equipment used for documentation, documentation created after providing care, and overall thoughts about and satisfaction with the SRT. The survey sample was from one rural and one urban facility in central Missouri. In addition, qualitative interviews were conducted with a chief medical officer and a physician champion regarding implementation issues, training, choice of SRT, and outcomes from their perspective. Seventy-one (60%) of the anticipated 125 surveys were returned. A total of 16 (23%) participants were practicing in internal medicine and 9 (13%) were practicing in family medicine. Fifty-six (79%) participants used a desktop and 14 (20%) used a laptop (2%) computer. SRT products from Nuance were the dominant SRT used by 59 participants (83%). Windows operating systems (Microsoft, Redmond, WA) was used by more than 58 (82%) of the survey respondents. With regard to user experience, 42 (59%) participants experienced spelling and grammatical errors, 15 (21%) encountered clinical inaccuracy, 9 (13%) experienced word substitution, and 4 (6%) experienced misleading medical information. This study shows critical issues of inconsistency, unreliability, and dissatisfaction in the functionality and usability of SRT. This merits further attention to improve the functionality and usability of SRT for better adoption within varying healthcare settings.

  7. Desprendimiento de retina

    L. Jaime Claramunt, Dr.


    Full Text Available El desprendimiento de retina (DR consiste en la separación entre la retina neurosensorial y el epitelio pigmentario subyacente. Su forma más frecuente es el DR regmatógeno, causado por una rotura en la retina. Se manifiesta generalmente como un defecto en el campo visual o mala visión. Si se pesquisa y trata oportunamente tiene buenas posibilidades de éxito. No obstante, sigue siendo una causa importante de mala visión y ceguera, por lo que su prevención tiene un rol fundamental.

  8. Dynamic fouling behaviors of submerged nonwoven bioreactor for filtration of activated sludge with different SRT.

    Chuang, Shun-Hsing; Lin, Po-Kuen; Chang, Wei-Chin


    The flux variations and resistances accumulated during filtration of activated sludge with sludge retention time (SRT) of 15, 30, and 60 days were analyzed to investigate the dynamic fouling behavior in a submerged nonwoven bioreactor. Different SRT values varied sludge condition and particle size distribution in the supernatants, which caused dissimilar fouling characteristics. Short-term fouling of the nonwoven bioreactor during filtration of activated sludge with SRT of 15 days was fully reversible, and the resistance percentages of solutes, colloids, and suspended solids were 6%, 27%, and 67%, respectively. On the other hand, significant increases of colloid resistance, such as with the filtration of activated sludge with SRT of 30 and 60 days, were related to the occurrence of irreversible fouling. The phenomenon of pore blocking by particles or colloids with size analogous to the pore of nonwoven fabric was a decisive factor leading to irreversible fouling in the large-pore materials.

  9. [A review of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer].

    Saito, Takeshi; Morohashi, Hajime; Hasebe, Tatsuya; Sakamoto, Yoshiyuki; Koyama, Motoi; Murata, Akihiko; Hakamada, Kenichi


    We retrospectively analyzed the efficacy of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer, with particular emphasis on local tumor control. Seven patients with 8 lesions underwent SRT for lung metastasis of colon cancer in our institution between February 2012 and February 2014. We judged the curative effect of SRT on the basis of tumor shrinkage observed on computed tomography (CT) scans. All lung metastases decreased in size, and local recurrence was not observed. SRT is a technique involving three-dimensional radiation, which decreases radiation exposure to neighboring normal tissues. The 2-year local tumor control rate for lung metastasis of colon cancer with SRT is 77.9%, and the 2-year survival rate is 53.7%. Our results, in which all patients achieved local control, suggest that SRT is a minimally aggressive treatment option for lung metastasis of colon cancer in cases where a pneumonectomy is difficult to perform. In the future, results from long-term studies are needed to validate our findings.

  10. Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans.

    Zarse, K; Schmeisser, S; Birringer, M; Falk, E; Schmoll, D; Ristow, M


    Resveratrol and SRT1720 have been shown to act as sirtuin activators that may ameliorate type 2 diabetes and metabolic diseases in mice. Moreover, resveratrol extends lifespan in model organisms like C. elegans, N. FURZERI, and possibly D. melanogaster. The aim of the study was to test whether pharmacological concentrations of resveratrol and SRT1720 are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. ELEGANS roundworms were maintained on agar plates and fed E. COLI strain OP50 bacteria. Resveratrol (5 micromolar, 500 nanomolar) or SRT1720 (1 micromolar, 100 nanomolar) was applied to the agar to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extends C. elegans lifespan by 3.6% (mean lifespan) and 3.4% (maximum lifespan). By unexpected contrast, SRT1720, which was previously proposed to be several hundred times more active than resveratrol, did not extend lifespan at none of the concentrations tested. Thus, in the model organisms C. elegans, resveratrol is capable of promoting longevity at a concentration that pharmacologically relevant and 20 times lower than previously published doses. The sirtuin activator SRT1720 did not extend lifespan, suggesting that in C. elegans, some relevant effects of resveratrol cannot be mimicked by SRT1720.

  11. Stereotactic radiotherapy in neovascular age-related macular degeneration: Real-life efficacy and morphological evaluation of the outer retina-choroid complex.

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore


    Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis.Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety.Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers.Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk.

  12. SRT project: tele-robotics maintenance of nuclear power plants

    Gomez-Santamaria, J. [Iberdrola SA, Madrid (Spain); Calleja, J.M.; Carmena, P. [Endesa, Madrid (Spain); Avello, A.; Rubio, Y.A. [CEIT-Centro de Estudias e Investigaciones Tecnicas de Guipuzcoa, San Sebastian (Spain)


    The main aim of the SRT project was to develop a family of robots to help in the operation of nuclear power plants. Four robotic systems were developed and this paper focuses on three of them: ANAES -a steam leak detector through noise analysis-, MALIBA -a master-slave tele-operation system with force feedback- and ROBICEN -a compact pneumatic wall climbing robot-. ANAES (the Spanish acronym of spectrum analysis) consists of a set of sensor heads attached to a computer. Each head has two microphones and a video camera installed on it, and a DC motor that rotates the head. The heads are shielded with lead and boron steel, especially near the video camera. The noise generated by the plant is recorded every day at the same time and the software compares the recorded noise with the mean values of past records. The system can discern whether the noise has remarkably changed and, through phase analysis of the sound recorded by both microphones, identifies the direction of arrival (DOA) of the new noise, probably a steam leak. Using several heads, the new noise source can be identified. The video camera can be used to ease the location of the steam leaks. The stationariness of the measured noise has been tested in C.N. Cofrentes -a Spanish BWR-6 reactor-. A finished system with six heads has recently been installed in the MSR (moisture separator reheater) of the same plant. MALIBA is a master-slave tele-operated system with force feedback. It consists of two robots: a Stewart platform used as master robot and an open chain robot used as slave. The slave robot follows faithfully the movements of the master, and the master robot can reflect a force proportional to the force exerted by the slave on the environment. Three tools have been developed for the slave robot: a robot hand that includes a small video camera, a pneumatic drill and a rectifier. The results obtained have shown its effectiveness for the designed operations. ROBICEN is a lightweight pneumatic robot

  13. Retina and Omega-3

    Giuseppe Querques; Raimondo Forte; Souied, Eric H.


    Over the last decade, several epidemiological studies based on food frequency questionnaires suggest that omega-3 polyunsaturated fatty acids could have a protective role in reducing the onset and progression of retinal diseases. The retina has a high concentration of omega-3, particularly DHA, which optimizes fluidity of photoreceptor membranes, retinal integrity, and visual function. Furthermore, many studies demonstrated that DHA has a protective, for example antiapoptotic, role in the ret...

  14. The influence of temperature and SRT on high-solid digestion of municipal sewage sludge.

    Jahn, L; Baumgartner, T; Svardal, K; Krampe, J


    The influence of temperature and solids retention time (SRT) on high-solid digestion of municipal sewage sludge was investigated in laboratory-scale reactors. Digestion with high-solid concentration reduces the required digestion volume and is advantageous for urban areas. The experimental conditions comprised total suspended solids (TSS) in digested sludge between 4.0 and 4.6%, temperatures in a range of 33 to 41 °C and the SRT between 10 and 25 d. High-solid digestion operates with increased NH4-N concentrations released from organic compounds. The anaerobic process can be limited by high NH4-N concentration and toxic NH3. In this study a stable digestion was observed up to 2,000 mg L(-1) NH4-N and 75 mg L(-1) NH3. Volatile suspended solids (VSS) and chemical oxygen demand removal was 53% and 57% respectively. However, digestion with 10 d SRT led to a declined VSS removal of 49%. The removal at 41 and 37 °C showed minor differences, while reduced NH4-N release and reduced methane production were observed at 33 °C. For economic reasons, high-solid digestion at 41 °C is not recommended, but will not impair VSS removal. The outcomes of this study confirm that digestion with up to 7.8% TSS in the feed is feasible for the tested temperatures and SRT down to 15 d.

  15. Identification of the srtC1 Transcription Start Site and Catalytically Essential Residues Required for Actinomyces oris T14V SrtC1 Activity


    Chen & K.P. Leung PCR primer UPM and gene specific primers: primer 2 for fimQ, primer 4 for fimP and primer 6 for srtC1. The amplified PCR products were...conducted in a chilled 2 mm Gap cuvette using a Pulser model of ECM630 ( BTX , San Diego, CA) with the following settings: 2.5 kV, 25 mF capacitor and 400O...generated by the use of primers 3 or 5 were used as the templates, both junctional regions were amplified. The two PCR products have the expected sizes

  16. A Serial Reaction Time (SRT) task with symmetrical joystick responding for nonhuman primates.

    Heimbauer, Lisa A; Conway, Christopher M; Christiansen, Morten H; Beran, Michael J; Owren, Michael J


    The serial reaction time (SRT) task is a simple procedure in which participants produce differentiated responses to each of a series of stimuli presented at varying locations. Learning about stimulus order is revealed through decreased latencies for structured versus randomized sequences. Although widely used with humans and well suited to nonhumans, this paradigm is little used in comparative research. In the present article, we describe an SRT procedure that uses colored circles as stimuli, a circular layout of locations, and symmetrical joystick deflections as responses. In two experiments, we showed that four rhesus macaques (Macaca mulatta) learned to track sequences up to eight items long, with three animals showing faster responding to repeating sequences than to randomized versions. After extended training, these participants also showed evidence of faster responding at all positions within repeating sequences. This method minimizes response effort, equates effort and travel distance across stimulus locations, and is applicable to any joystick-capable species.

  17. Corpus vitreum, retina og chorioidea biopsi

    Scherfig, Erik Christian Høegh


    oftalmology, biopsy, choroid, corpus vitreum, retina, malignant melanoma, biopsy technic, retinoblastoma......oftalmology, biopsy, choroid, corpus vitreum, retina, malignant melanoma, biopsy technic, retinoblastoma...

  18. [Research and development of artificial retina material].

    Hu, Ning; Yang, Jun; Peng, Chenglin; Wang, Xing; Zhang, Sijie; Zhang, Ying; Zheng, Erxin


    The application of artificial retina was introduced. The principal characteristics of artificial retina material were reviewed in particular. Moreover, the recent research development and application prospect were discussed.

  19. Correction to the 2005 paper: "Digit Selection for SRT Division and Square Root"

    Kornerup, Peter


    It has been pointed out by counterexamples in a 2013 paper in the IEEE Transactions on Computers [1], that there is an error in the previously ibid.\\ in 2005 published paper [2] on the construction of valid digit selection tables for SRT type division and square root algorithms. The error has been corrected, and new results found on selection constants for maximally redundant digit sets.

  20. The effect of SRT on nitrate formation during autotrophic nitrogen removal of anaerobically treated wastewater.

    Lee, Po-Heng; Kwak, Wonji; Bae, Jeaho; McCarty, Perry L


    Autotrophic nitrogen removal, coupling nitritation (ammonium to nitrite) with anaerobic ammonium oxidation (anammox), offers a promising nitrogen-removal alternative, especially for post-treatment of anaerobically-treated wastewater. However, previous reports suggest that less than 90% total nitrogen removal should be expected with this process alone because over 10% of the ammonium removed will be converted to nitrate. This is caused because nitrite conversion to nitrate is required for reduction of carbon dioxide to cell carbon. However, recent research results suggest that more limited nitrate formation of only a few per cent sometimes occurs. It was hypothesized such lower nitrate yields may result from use of long solids retention times (SRT) where net biological yields are low, and providing that the ratio of oxygen added to influent ammonium concentrations is maintained at or below 0.75 mol/mol. Overall reaction equations were developed for each process and combined to evaluate the potential effect of SRT on process stoichiometry. The results support the use of a long SRT to reduce net cell yield, which in turn results in a small percentage conversion to nitrate during ammonium removal and high total nitrogen removals in the range of 90 to 94%.

  1. The Retina Algorithm

    CERN. Geneva; PUNZI, Giovanni


    Charge particle reconstruction is one of the most demanding computational tasks found in HEP, and it becomes increasingly important to perform it in real time. We envision that HEP would greatly benefit from achieving a long-term goal of making track reconstruction happen transparently as part of the detector readout ("detector-embedded tracking"). We describe here a track-reconstruction approach based on a massively parallel pattern-recognition algorithm, inspired by studies of the processing of visual images by the brain as it happens in nature ('RETINA algorithm'). It turns out that high-quality tracking in large HEP detectors is possible with very small latencies, when this algorithm is implemented in specialized processors, based on current state-of-the-art, high-speed/high-bandwidth digital devices.

  2. Effects of sludge retention time (SRT) and biosurfactant on the removal of polyaromatic compounds and toxicity

    Sponza, Delia Teresa, E-mail: [Dokuz Eylul University, Engineering Faculty, Environmental Engineering Department, Buca Kaynaklar Campus, 35160 Izmir (Turkey); Gok, Oguzhan [Dokuz Eylul University, Engineering Faculty, Environmental Engineering Department, Buca Kaynaklar Campus, 35160 Izmir (Turkey)


    Graphical abstract: Acute toxicities in (a) influent wastewater (EC{sub 50} = 45.02 ng ml{sup -1}) and (b) effluent wastewater in aerobic activated sludge reactor at SRT = 25 days (EC{sub 6} = 5.30 ng ml{sup -1}). Highlights: Black-Right-Pointing-Pointer Over 90% of the total PAHs was removed at Rhamnolipid and sludge retention time of 15 mg l{sup -1} and 25 days. Black-Right-Pointing-Pointer 93% of the COD originating from the inert organics was removed in the aerobic reactor. 96-97% of the Rhamnolipid was biodegraded. Black-Right-Pointing-Pointer The EC50 value was reduced from EC{sub 50} = 45.02 ng ml{sup -1} to C{sub 6} = 5.30 ng ml{sup -1} with Daphnia magna. Toxicity removals originating from the PAHs were 96%. - Abstract: A laboratory-scale aerobic activated sludge reactor (AASR) system was employed to investigate the effects of SRT on the removal of three less hydrophobic and six more hydrophobic PAHs in the presence of rhamnolipid (RD), emulsan (EM) and surfactine (SR) biosurfactants. Among the biosurfactants it was found that RD exhibits a better performance than the others in the removal of PAHs. At a RD of 15 mg l{sup -1} aerobic treatment for 25 days SRT was enough to remove over 90% of the total PAHs, 88% of the COD originating from the inert organics (COD{sub inert}) and 93% of the COD originating from the inert soluble microbial products (COD{sub imp}). At this SRT and RD concentration, about 96-98% of the RD was biodegraded by the AASR system, 1.2-1.4% was accumulated in the system, 1.1-1.3% was released in the effluent, and 1.2-1.4% remained in the waste sludge. The addition of electron acceptors (NO{sub 3}{sup -1}, SO{sub 4}{sup -2}) and increasing of temperature up to 45 Degree-Sign C enhanced the PAH yields. The most effective PAH degradation occurred in high-oxygenated and neutral pH conditions. The PAH concentration affecting half of the Daphnia magna organism (EC{sub 50} value) was reduced from EC{sub 50} = 45.02 ng ml{sup -1} to the PAH

  3. The proteome of human retina.

    Zhang, Pingbo; Dufresne, Craig; Turner, Randi; Ferri, Sara; Venkatraman, Vidya; Karani, Rabia; Lutty, Gerard A; Van Eyk, Jennifer E; Semba, Richard D


    The retina is a delicate tissue that detects light, converts photochemical energy into neural signals, and transmits the signals to the visual cortex of the brain. A detailed protein inventory of the proteome of the normal human eye may provide a foundation for new investigations into both the physiology of the retina and the pathophysiology of retinal diseases. To provide an inventory, proteins were extracted from five retinas of normal eyes and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed in duplicate using LC-MS/MS on an Orbitrap Elite mass spectrometer. A total of 3436 nonredundant proteins were identified in the human retina, including 20 unambiguous protein isoforms, of which eight have not previously been demonstrated to exist at the protein level. The proteins identified in the retina included most of the enzymes involved in the visual cycle and retinoid metabolism. One hundred and fifty-eight proteins that have been associated with age-related macular degeneration were identified in the retina. The MS proteome database of the human retina may serve as a valuable resource for future investigations of retinal biology and disease. All MS data have been deposited in the ProteomeXchange with identifier PXD001242 (

  4. OsSRT1 is involved in rice seed development through regulation of starch metabolism gene expression.

    Zhang, Hua; Lu, Yue; Zhao, Yu; Zhou, Dao-Xiu


    OsSRT1 is a NAD(+)-dependent histone deacetylase, closely related to the human SIRT6 that plays key roles in genome stability and metabolic homeostasis. In this work, we investigated the role of OsSRT1 in rice seed development. Down-regulation of OsSRT1 induced higher expression of Rice Starch Regulator1 (RSR1) and amylases genes in developing seeds, which resulted in a decrease of starch synthesis and an increase of starch degradation, leading to abnormal seed development. ChIP assay showed that OsSRT1 was required to reduce histone H3K9 acetylation on starch metabolism genes and transposons in developing seeds. In addition, OsSRT1 was detected to directly bind to starch metabolism genes such as OsAmy3B, OsAmy3E, OsBmy4, and OsBmy9. Our results suggested that OsSRT1-mediated histone deacetylation is involved in starch accumulation and transposon repression to regulate normal seed development.

  5. Influence of family, religion, and social conformity on client participation in sexual reorientation therapy.

    Maccio, Elaine M


    This study examined the likelihood of participating in sexual reorientation therapy (SRT) based on actual or expected family reactions to the disclosure of one's same-sex sexuality, religious fundamentalism, social conformity, and several demographic variables. A sample of 52 SRT participants and 211 SRT nonparticipants who had ever identified as gay, lesbian, or bisexual completed a survey either online or in hardcopy format. Actual or expected negative family reactions, high religious fundamentalism, and identifying as spiritual significantly increased one's odds of participating in SRT. The findings are essential for preparing practitioners in any clinical practice setting to work with clients struggling with their sexuality.

  6. Influence of SRT and HRT on Bioprocess Performance in Anaerobic Membrane Bioreactors Treating Municipal Wastewater.

    Dong, Qirong; Parker, Wayne; Dagnew, Martha


    This study investigated the impact of Solid Retention Time (SRT) (40 to 100 days) and Hydraulic Retention Time (HRT) (2.5 to 8.5 hours) on the treatment of municipal wastewater in pilot and bench scale AnMBRs. The results revealed good permeate quality with respect to concentrations of COD (<40 mg/L) and BOD5 (<10 mg/L) was achieved under all conditions. Over the range of values tested SRT and HRTdid not significantly influence COD and BOD5 removal efficiencies. Extended SRTs resulted in reduced sludge production and enhanced methane production. Oversaturation of dissolved methane in permeate appears to have been responsible for a consistent lack of COD mass balance closure in all tests. After calibration of biokinetic coefficients, PetWin 4 (EnviroSim Canada) was found to effectively simulate the concentrations of particulate COD, readily biodegradable COD and acetic acid over a range of SRTs and HRTs. The calibrated saturation coefficients for hydrolysis and aceticlastic methanogenesis processes were comparable to those reported in literature. The saturation coefficient of fermentation was significantly lower than those reported in literature. The simulated methane mass flows were consistently higher than the measured values which was consistent with the lack of COD mass balance closure and was attributed to reduction of sulfate and oversaturation of the permeate with respect to Henry's Law.

  7. The Sirt1 activator SRT3025 expands hematopoietic stem and progenitor cells and improves hematopoiesis in Fanconi anemia mice

    Qing-Shuo Zhang


    Full Text Available Fanconi anemia is a genetic bone marrow failure syndrome. The current treatment options are suboptimal and do not prevent the eventual onset of aplastic anemia requiring bone marrow transplantation. We previously showed that resveratrol, an antioxidant and an activator of the protein deacetylase Sirt1, enhanced hematopoiesis in Fancd2 mutant mice and improved the impaired stem cell quiescence observed in this disease. Given that Sirt1 is important for the function of hematopoietic stem cells, we hypothesized that Sirt1 activation may improve hematopoiesis. Indeed, Fancd2−/− mice and wild-type mice treated with the selective Sirt1 activator SRT3025 had increased numbers of hematopoietic stem and progenitor cells, platelets and white blood cells. SRT3025 was also protective against acetaldehyde-induced hematopoietic damage. Unlike resveratrol, however, SRT3025 did not affect stem cell quiescence, suggesting distinct mechanisms of action. Conditional deletion of Sirt1 in hematopoietic cells did not abrogate the beneficial effects of SRT3025, indicating that the drug did not act by directly stimulating Sirt1 in stem cells, but must be acting indirectly via extra-hematopoietic effects. RNA-Seq transcriptome analysis revealed the down-regulation of Egr1–p21 expression, providing a potential mechanism for improved hematopoiesis. Overall, our data indicate that SRT3025 or related compounds may be beneficial in Fanconi anemia and other bone marrow failure syndromes.

  8. The Sirt1 activator SRT3025 expands hematopoietic stem and progenitor cells and improves hematopoiesis in Fanconi anemia mice.

    Zhang, Qing-Shuo; Deater, Matthew; Schubert, Kathryn; Marquez-Loza, Laura; Pelz, Carl; Sinclair, David A; Grompe, Markus


    Fanconi anemia is a genetic bone marrow failure syndrome. The current treatment options are suboptimal and do not prevent the eventual onset of aplastic anemia requiring bone marrow transplantation. We previously showed that resveratrol, an antioxidant and an activator of the protein deacetylase Sirt1, enhanced hematopoiesis in Fancd2 mutant mice and improved the impaired stem cell quiescence observed in this disease. Given that Sirt1 is important for the function of hematopoietic stem cells, we hypothesized that Sirt1 activation may improve hematopoiesis. Indeed, Fancd2(-/-) mice and wild-type mice treated with the selective Sirt1 activator SRT3025 had increased numbers of hematopoietic stem and progenitor cells, platelets and white blood cells. SRT3025 was also protective against acetaldehyde-induced hematopoietic damage. Unlike resveratrol, however, SRT3025 did not affect stem cell quiescence, suggesting distinct mechanisms of action. Conditional deletion of Sirt1 in hematopoietic cells did not abrogate the beneficial effects of SRT3025, indicating that the drug did not act by directly stimulating Sirt1 in stem cells, but must be acting indirectly via extra-hematopoietic effects. RNA-Seq transcriptome analysis revealed the down-regulation of Egr1-p21 expression, providing a potential mechanism for improved hematopoiesis. Overall, our data indicate that SRT3025 or related compounds may be beneficial in Fanconi anemia and other bone marrow failure syndromes.

  9. The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet

    Sarah J. Mitchell


    Full Text Available The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1, an NAD+-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice.

  10. [Implantation of the artificial retina].

    Yagi, T; Hayashida, Y


    In some degenerative retinal diseases, e.g., retinitis pigmentosa and age-related macular degeneration, the photoreceptors are destroyed to cause serious visual defects. Recent studies on blind human subjects revealed that a large number of ganglion cells remains intact and is capable of transmitting signals to the brain to evoke partial visual perception. This provided hope to compensate for the visual defects with retinal prostheses. The recent progress of microfabrication technique made it possible to implement the Vary Large Scale Integrated circuit, the artificial retina, which emulates a part of retinal function. The idea of implanting the artificial retina to the patients was proposed recently and experiments using animals have been put into practice. This article surveys the front line of the artificial retina implantation.

  11. Using stem cells to mend the retina in ocular disease.

    Bull, Natalie D; Martin, Keith R


    Retinal degenerative diseases are the leading cause of incurable blindness worldwide. Furthermore, existing pharmacological and surgical interventions are only partially effective in halting disease progression, thus adjunctive neuroprotective strategies are desperately needed to preserve vision. Stem cells appear to possess inherent neuroprotective abilities, at least in part by providing neurotrophic support to injured neurons. Advances in stem cell biology offer the hope of new therapies for a broad range of neurodegenerative conditions, including those of the retina. Experimental cell-mediated therapies also hint at the tantalizing possibility of achieving retinal neuronal replacement and regeneration, once cells are lost to the disease process. This article summarizes the latest advances in cell therapies for neuroprotection and regeneration in neurodegenerative pathologies of both the inner and outer retina.

  12. Correlation between heterogeneity index (HI) and gradient index (GI) for high dose stereotactic radiotherapy/radiosurgery (SRT/SRS)

    Tas, B.; Durmus, I. F.; Okumus, A.; Uzel, O. E.


    To evaluate between Heterogeneity Index (HI) and Gradient Index (GI) correlation for high dose Stereotactic radiotherapy (SRT) / Stereotactic radiosurgery (SRS) using Versa HD® lineer accelerator. Nine patients with single metastasis were used in this study. Patient's treatment planning were performed using Monaco5.1® Treatment planning system (TPS) with non-coplanar 6MV Flattening filter free (FFF) beams by partial Volumetric modulated arc therapy (VMAT) tecnique for each patient. We determined three different size of metastasis catagory which are less than 1cc, between 1cc and 5cc and larger than 5cc volume. Also, three different HI were calculated for each patients. These are 1.10, 1.20 and 1.30. Mean GI was determined 8.57±2.2 for 1.10 HI, 7.23±1.7 for 1.20 HI and 6.0±1.1 for 1.30 HI for less than 1cc metastasis. Then GI was determined 4.77±0.4 for 1.10 HI, 4.37±0.3 for 1.20 HI and 3.97±0.3 for 1.30 HI for between 1cc and 5cc metastasis. Finally, GI was determined 4.00±0.5 for 1.10 HI,3.63±0.5 for 1.20 HI and 3.27±0.4 for 1.30 HI for larger than 5cc metastasis. These results show that GI depends on significantly size and HI of metastasis especially for less than 1cc.

  13. Do artists see their retinas?

    Perdreau, F.A.G.; Cavanagh, P.


    Our perception starts with the image that falls on our retina and on this retinal image, distant objects are small and shadowed surfaces are dark. But this is not what we see. Visual constancies correct for distance so that, for example, a person approaching us does not appear to become a larger per

  14. Status report of the SRT radiotelescope control software: the DISCOS project

    Orlati, A.; Bartolini, M.; Buttu, M.; Fara, A.; Migoni, C.; Poppi, S.; Righini, S.


    The Sardinia Radio Telescope (SRT) is a 64-m fully-steerable radio telescope. It is provided with an active surface to correct for gravitational deformations, allowing observations from 300 MHz to 100 GHz. At present, three receivers are available: a coaxial LP-band receiver (305-410 MHz and 1.5-1.8 GHz), a C-band receiver (5.7-7.7 GHz) and a 7-feed K-band receiver (18-26.5 GHz). Several back-ends are also available in order to perform the different data acquisition and analysis procedures requested by scientific projects. The design and development of the SRT control software started in 2004, and now belongs to a wider project called DISCOS (Development of the Italian Single-dish COntrol System), which provides a common infrastructure to the three Italian radio telescopes (Medicina, Noto and SRT dishes). DISCOS is based on the Alma Common Software (ACS) framework, and currently consists of more than 500k lines of code. It is organized in a common core and three specific product lines, one for each telescope. Recent developments, carried out after the conclusion of the technical commissioning of the instrument (October 2013), consisted in the addition of several new features in many parts of the observing pipeline, spanning from the motion control to the digital back-ends for data acquisition and data formatting; we brie y describe such improvements. More importantly, in the last two years we have supported the astronomical validation of the SRT radio telescope, leading to the opening of the first public call for proposals in late 2015. During this period, while assisting both the engineering and the scientific staff, we massively employed the control software and were able to test all of its features: in this process we received our first feedback from the users and we could verify how the system performed in a real-life scenario, drawing the first conclusions about the overall system stability and performance. We examine how the system behaves in terms of network

  15. [Influence of cycle length shortening, atropine and beta-receptor blockage on sinus node recovery time (SRT) in patients with healthy sinus node (author's transl)].

    Runge, M; Wohlberg, H; Luckmann, E; Pantlen, H


    Sinus node recovery time (SRT) was measured in 30 patients with healthy sinus nodes to examine the influence of the increase in atrial frequency, atropine and beta-receptor blockade. The measurements were performed following pacing with 3 atrial frequencies before and after administration of 1 mg atropine i.v. (13 patients) and 0.4 mg prindolol (Visken) i.v. (17 patients). Total group; Increase of frequency alone caused prolongation of the SRT in 17 patients and shortening in 13 patients. Atropine group: Blockade of the parasympathicus alone induced a highly significant reduction in the SRT. Simultaneous increase in frequency and blockade of the parasympathicus led to greater SRT-shortening during low frequency than with high frequency. This interrelationship of frequency and blockade of the parasympathicus influencing the SRT is statistically significant. Visken-group: Blockade of the sympathicus causes a highly significant prolongation of the SRT. Simultaneous increase in frequency and blockade of the sympathicus led to greater SRT-prolongation during low frequency than with high frequency. This interrelationship of frequency and blockade of the sympathicus influencing the SRT has slight statistical significance. The results are discussed in respect to the electrophysiological influences of atrial cycle length shortening, acetylcholine and catecholamines on the sinus node, the perinodal atrial fibres and the atrial working myocardium.

  16. Stem/progenitor cells: a potential source of retina-specific cells for retinal repair.

    Bi, Yong-Yan; Feng, Dong-Fu; Pan, Dong-Chao


    Retinal injury generally results in permanent visual disturbance or even blindness. Any effort to restore vision in such condition would require replacement of the highly specialized retinal cells. Stem/progenitor cells have been proposed as a potential source of new retina-specific cells to replace those lost due to retina injury. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for retina injury. A wide range of stem/progenitor cells from various sources is currently being investigated for the treatment of retinal injury. This article reviews the recent achievements about stem/progenitor cell source for retinal repair.

  17. Towards photovoltaic powered artificial retina


    The aim of this article is to provide an overview of current and future concepts in the field of retinal prostheses, and is focused on the power supply based on solar energy conversion; we introduce the possibility of using PV minimodules as power supply for a new concept of retinal prostheses: Photovoltaic Powered Artificial Retina (PVAR). Main characteristics of these PV modules are presented showing its potential for this application. Peer Reviewed

  18. SU-E-T-536: LINAC-Based Single Isocenter Frameless SRT for Brain Metastases

    Liu, B; Zhang, L; Rigor, N; Kim, J [City of Hope Foundation, CA (United States)


    Purpose: Single-isocenter Stereotactic Radiotherapy of multiple brain metastases with Varian 21 IX LINAC, using Aktina Pinpoint system for patient setup. Methods: In 2014, five single-isocenter RapidArc SRT plans were delivered to five patients with 2 to 8 brain metastases using Varian 21 IX. Aktina Pinpoint system was used for setup and 2mm PTV margin were used. CBCT was acquired before and after the beam delivery. The prescription is 2100 cGy in 3 fractions. Eclipse planning system was used for treatment planning. Depending on the number of metastases and their locations, 1 to 5 coplanar or non coplanar arcs were used. Typically, 2 or 3 arcs are used. IMRT QAs were performed by comparing an A1SL ion chamber point dose measurement in solid water phantom to point dose of the plan; also, based on EPID measurement, 3D spatial dose was calculated using DosimetryCheck software package from MathResolutions Inc. The EPID system has an active area of 40cm by 30cm with 1024 by 768 photodiodes, which corresponds to a resolution of 0.4mm by 0.4mm pixel dimension. Results: for all the plans, at least 95% PTV coverage was achieved for full prescription dose, with plan normalization > 75%. RTOG conformity indices are less than 1.1 and Paddick gradient indices are less than 4.5. The distance from prescription IDL to 50% IDL increases as the number of metastases increases, and it ranges from 0.6mm to 0.8mm. Treatment time varies from 10mins to 30mins, depending on the number of arcs and if the arcs are coplanar. IMRT QA shows that the ion chamber measurement agree with the eclipse calculation within 3%, and 95% of the points passed Gamma, using 3% dose difference and 3mm DTA Conclusion: High quality single isocenter RapidArc SRT plan can be optimized and accurately delivered using Eclipse and Varian 21IX.

  19. Construction and characteristic of srtA gene mutant strain of Streptococcus suis 2%猪链球菌2型srtA基因缺失菌株的构建及生物学特性

    吴涛; 常海涛; 谭臣; 付婷; 司有辉; 贝为成; 陈焕春


    In the present study,srtA gene mutant strain was constructed by using the thermo-sensitive suicide vector pSET4s and confirmed by PCR and Southern blotting.The results showed that the construction of the mutant strain was successful,named SC211.In addition complementation mutant strain was constructed by using the E.coli/Streptococcus shuttle vector pAT18,named SC212.The characteristic of SC211 and SC212 was further researched.The virulence of different strains was determined by animal infection,which demonstrated that the virulence was decreased clearly when the srtA gene knocked out.The virulence of the mutant was restored when strain mediated by plasmid-containing the srtA gene.However,it could not reach the level of the wild type.The hemolytic activity of the srtA gene mutant strain and the complementation strain had no difference when compared with the wild type strain.The adherence to the Hep2 cell of the srtA gene mutant strain degraded obviously,and the adherence to the Hep2 cell of the complementation strain had no obvious difference compared with the wild type.%扩增了srtA基因的上、下游同源臂P1和P2及其全长序列,利用温度敏感型"自杀性"质粒pSET4s构建了重组质粒pSET4s-P1-P2,并将该质粒电转化入野生菌株SS2(SC21)中,通过抗生素和温度双重筛选,得到srtA基因缺失菌株,命名SC211.同时,将srtA基因定向插入穿梭质粒pAT18,构建穿梭质粒pAT18-srtA,并将该质粒电转入srtA基因缺失菌株SC211中,通过抗生素筛选,得到质粒介导的srtA基因互补菌株SC212.通过PCR、South-ern blotting等对缺失突变菌株和互补菌株进行了鉴定.对基因缺失突变菌株和回复菌株传代培养遗传稳定性试验结果显示,缺失突变菌株和互补菌株能够稳定遗传.比较了基因缺失突变菌株、互补菌株及野生菌株的生长特性、溶血活性、细胞粘附特性,结果表明,3个菌株的生长速度、溶血活性没有

  20. SRT as a receiver in a bistatic radar space debris configuration

    Pisanu, T.; Concu, R.; Gaudiomonte, F.; Marongiu, P.; Melis, A.; Serra, G.; Urru, E.; Valente, G.; Portelli, C.; Muntoni, G.; Bianchi, G.; Comoretto, G.; Dolce, F.; Paoli, J.; Reali, M.; Villadei, W.


    Space debris is becoming a very important and urgent problem for present and future space activities. For that reason many public and private Institutions in the world are being involved in order to monitor and control the debris population increase and to understand which facilities can be used for improving the surveillance and tracking capabilities. In this framework in 2014 we performed some preliminary observations in a beam parking, CW mode and a bistatic configuration, with a transmitter of 4 kW of the Italian Air Force and the SRT (Sardinia Radio Telescope) a 64 meters radiotelescope used as a receiver. We performed the observations in P band at 410 MHz, receiving the signal diffused from some debris of different sizes and distances in LEO orbit, in order to understand the performances and capabilities of the system. In this article we will describe the results of this observations campaign, the simulation work done for preparing it, the RCS (radar cross section) observed, the level of the received signals, the Doppler measurements, and the work we are doing for developing a new and higher performing digital back end, able to process the data received.

  1. Particulate organics degradation and sludge minimization in aerobic, complete SRT bioreactors.

    Amanatidou, Elisavet; Samiotis, Georgios; Trikoilidou, Eleni; Tsikritzis, Lazaros


    The study evaluates the assumption that in activated sludge processes and under specific operating conditions, the considered unbiodegradable particulate organic fractions of influent (XU) organic solids and biomass decay residues (cell debris, XE) are degraded. The evaluation was performed by comparing sludge observed yield (Yobs) evolution in two full scale, complete solids retention time (SRT), aerobic bioreactors, to the predictions of two activated sludge models. The results showed that in steady state operating conditions of complete solids retention AS processes very low solids accumulation occur. In these conditions, solids accumulation is slightly affected by kinetic coefficients and significantly affected by XU and XE degradation rates. High endogenous residues degradation rate values of 0.05 d(-1) and 0.02 d(-1) were estimated for the two bioreactors, resulting in low solids accumulation, calculated at 1.6 tons and 3.59 tons per year respectively, of which 1.37 and 0.87 tons were non volatile suspended solids. Depending on WWTP operating conditions the endogenous residues degradation rate is the limiting factor of solids accumulation and consequently for particulate organics degradation.

  2. A Computational Framework for Realistic Retina Modeling.

    Martínez-Cañada, Pablo; Morillas, Christian; Pino, Begoña; Ros, Eduardo; Pelayo, Francisco


    Computational simulations of the retina have led to valuable insights about the biophysics of its neuronal activity and processing principles. A great number of retina models have been proposed to reproduce the behavioral diversity of the different visual processing pathways. While many of these models share common computational stages, previous efforts have been more focused on fitting specific retina functions rather than generalizing them beyond a particular model. Here, we define a set of computational retinal microcircuits that can be used as basic building blocks for the modeling of different retina mechanisms. To validate the hypothesis that similar processing structures may be repeatedly found in different retina functions, we implemented a series of retina models simply by combining these computational retinal microcircuits. Accuracy of the retina models for capturing neural behavior was assessed by fitting published electrophysiological recordings that characterize some of the best-known phenomena observed in the retina: adaptation to the mean light intensity and temporal contrast, and differential motion sensitivity. The retinal microcircuits are part of a new software platform for efficient computational retina modeling from single-cell to large-scale levels. It includes an interface with spiking neural networks that allows simulation of the spiking response of ganglion cells and integration with models of higher visual areas.

  3. Retina

    ... Foundations of Clinical Ophthalmology . 2013 ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:vol 1;chap 19. Coleman ... EA, eds. Duane's Ophthalmology . 2013 ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:vol 3;chap 3. Yanoff ...

  4. The Functional Architecture of the Retina.

    Masland, Richard H.


    Examines research related to the retina's coding of visual input with emphasis on the organization of two kinds of ganglion cell receptive fields. Reviews current techniques for examining the shapes and arrangement in the retina of entire populations of nerve cells. (ML)

  5. Study of the Effect of SRT on Microbial Diversity in Laboratory-scale Sequencing Batch Reactors Using Acclimated and Non-Acclimated Seed

    Tellez, Berenice


    Solids Retention Time (SRT) is an important design parameter in activated sludge wastewater treatment systems. In this study, the effect of SRT on the bacterial community structure and diversity was examined in replicate lab-scale activated sludge sequencing batch reactors were operated for a period of 8 weeks and seeded with acclimated or non-acclimated sludge. Four SBRs (acclimated) were set up as duplicates and operated at an SRT of 2 days, and another set of four SBRs (non-acclimated) were operated at an SRT of 10 days. To characterize the microbial community in the SBRs, 16S rRNA gene pyrosequencing was used to measure biodiversity and to assess the reproducibility and stability of the bacterial community structure in replicate reactors. Diversity results showed that SBRs operated at an SRT of 10 days are more diverse than SBRs operated at an SRT of 2 days. This suggests that engineering decision could enhance diversity in activated sludge systems. Cluster analysis based on phylogenetic information revealed that the bacterial community structure was not stable and replicated SBRs evolved differently.

  6. Glycogen metabolism in the rat retina.

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío


    It has been reported that glycogen levels in retina vary with retinal vascularization. However, the electrical activity of isolated retina depends on glucose supply, suggesting that it does not contain energetic reserves. We determined glycogen levels and pyruvate and lactate production under various conditions in isolated retina. Ex vivo retinas from light- and dark-adapted rats showed values of 44 +/- 0.3 and 19.5 +/- 0.4 nmol glucosyl residues/mg protein, respectively. The glycogen content of retinas from light-adapted animals was reduced by 50% when they were transferred to darkness. Glycogen levels were low in retinas incubated in glucose-free media and increased in the presence of glucose. The highest glycogen values were found in media containing 20 mm of glucose. A rapid increase in lactate production was observed in the presence of glucose. Surprisingly, glycogen levels were the lowest and lactate production was also very low in the presence of 30 mm glucose. Our results suggest that glycogen can be used as an immediate accessible energy reserve in retina. We speculate on the possibility that gluconeogenesis may play a protective role by removal of lactic acid.

  7. Role of dopamine in distal retina.

    Popova, E


    Dopamine is the most abundant catecholamine in the vertebrate retina. Despite the description of retinal dopaminergic cells three decades ago, many aspects of their function in the retina remain unclear. There is no consensus among the authors about the stimulus conditions for dopamine release (darkness, steady or flickering light) as well as about its action upon the various types of retinal cells. Many contradictory results exist concerning the dopamine effect on the gross electrical activity of the retina [reflected in electroretinogram (ERG)] and the receptors involved in its action. This review summarized current knowledge about the types of the dopaminergic neurons and receptors in the retina as well as the effects of dopamine receptor agonists and antagonists on the light responses of photoreceptors, horizontal and bipolar cells in both nonmammalian and mammalian retina. Special focus of interest concerns their effects upon the diffuse ERG as a useful tool for assessment of the overall function of the distal retina. An attempt is made to reveal some differences between the dopamine actions upon the activity of the ON versus OFF channel in the distal retina. The author has included her own results demonstrating such differences.

  8. Age related macular degeneration and drusen: neuroinflammation in the retina.

    Buschini, Elisa; Piras, Antonio; Nuzzi, Raffaele; Vercelli, Alessandro


    Inflammation protects from dangerous stimuli, restoring normal tissue homeostasis. Inflammatory response in the nervous system ("neuroinflammation") has distinct features, which are shared in several diseases. The retina is an immune-privileged site, and the tight balance of immune reaction can be disrupted and lead to age-related macular disease (AMD) and to its peculiar sign, the druse. Excessive activation of inflammatory and immunological cascade with subsequent induction of damage, persistent activation of resident immune cells, accumulation of byproducts that exceeds the normal capacity of clearance giving origin to a chronic local inflammation, alterations in the activation of the complement system, infiltration of macrophages, T-lymphocytes and mast-cells from the bloodstream, participate in the mechanisms which originate the drusen. In addition, aging of the retina and AMD involve also para-inflammation, by which immune cells react to persistent stressful stimuli generating low-grade inflammation, aimed at restoring function and maintaining tissue homeostasis by varying the set point in relation to the new altered conditions. This mechanism is also seen in the normal aging retina, but, in the presence of noxious stimuli as in AMD, it can become chronic and have an adverse outcome. Finally, autophagy may provide new insights to understand AMD pathology, due to its contribution in the removal of defective proteins. Therefore, the AMD retina can represent a valuable model to study neuroinflammation, its mechanisms and therapy in a restricted and controllable environment. Targeting these pathways could represent a new way to treat and prevent both exudative and dry forms of AMD.

  9. Induction of ectopic retina-like tissue by transgenic expression of neurogenin.

    Run-Tao Yan

    Full Text Available Degeneration of retinal neurons is an underlying cause of several major types of blinding diseases, and effective therapies remain to be developed. The suppositive strategy of repopulating a degenerative retina with new cells generated onsite faces serious challenges, because the mammalian retina seems to lack the ability to regenerate itself or replace its lost neurons. We investigated the possibility of using a transcriptional factor with proneural activities to reprogram ocular tissue with regenerative capability to give rise to retinal cells. Transgenic mice were generated with DNA constructs that targeted the expression in the retinal pigment epithelium of proneural gene neurogenin1 from the promoter of Bestrophin1, or neurogenin3 from RPE65 promoter. Here we report the presence of ectopic retina-like tissue in some of the transgenic mice, young and aged. The ectopic retina-like tissue contained cells positive for photoreceptor proteins Crx, recoverin, red opsin, and rhodopsin, and cells positive for proteins that label other types of retinal neurons, including AP2α and Pax6 for amacrine cells, Otx2 for bipolar cells, and Brn3A for ganglion cells. The retina-like tissue often co-existed with darkly pigmented tissue positive for RPE proteins: cytokeratin 18, Otx2, and RPE65. The ectopic retina-like tissue was detected in the subretinal space, including two retinae co-existing in the same eye, and/or in the optic nerve or in the vicinity of the optic nerve head. On rare occasions, it was detected in the choroid and in the vicinity of the ciliary body. The presence of ectopic retina-like tissue in the transgenic mouse supports the possibility of inducing retinal regeneration in the mammalian eyes through gene-directed reprograming.

  10. Color sensitive retina based on bacteriorhodopsin.

    Frydrych, M; Silfsten, P; Parkkinen, S; Parkkinen, J; Jaaskelainen, T


    Bacteriorhodopsin (BR), a membrane protein of a microorganism Halobacterium salinarium has been studied since the 80's as a potential material for information technology. The information processing applications of BR employ either photochromic or photoelectric properties of the protein. In this study we discuss about design principles and describe our study of the use of bacteriorhodopsin as a sensor material for a color sensitive artificial retina. This retina includes low-level processing of input information. The design of a color sensitive matrix element, the self-organizing color adaptation algorithm and a system model for the retina are presented.

  11. The estrogenic retina: The potential contribution to healthy aging and age-related neurodegenerative diseases of the retina.

    Cascio, Caterina; Deidda, Irene; Russo, Domenica; Guarneri, Patrizia


    These last two decades have seen an explosion of clinical and epidemiological research, and basic research devoted to envisage the influence of gender and hormonal fluctuations in the retina/ocular diseases. Particular attention has been paid to age-related disorders because of the overlap of endocrine and neuronal dysfunction with aging. Hormonal withdrawal has been considered among risk factors for diseases such as glaucoma, diabetic retinopathy and age-related macular disease (AMD), as well as, for Alzheimer's disease, Parkinson's disease, or other neurodegenerative disorders. Sex hormones and aging have been also suggested to drive the incidence of ocular surface diseases such as dry eye and cataract. Hormone therapy has been approached in several clinical trials. The discovery that the retina is another CNS tissue synthesizing neurosteroids, among which neuroactive steroids, has favored these studies. However, the puzzling data emerged from clinical, epidemiological and experimental studies have added several dimensions of complexity; the current landscape is inherently limited to the weak information on the influence and interdependence of endocrine, paracrine and autocrine regulation in the retina, but also in the brain. Focusing on the estrogenic retina, we here review our knowledge on local 17β-oestradiol (E2) synthesis from cholesterol-based neurosteroidogenic path and testosterone aromatization, and presence of estrogen receptors (ERα and ERβ). The first cholesterol-limiting step and the final aromatase-limiting step are discussed as possible check-points of retinal functional/dysfunctional E2. Possible E2 neuroprotection is commented as a group of experimental evidence on excitotoxic and oxidative retinal paradigms, and models of retinal neurodegenerative diseases, such as glaucoma, diabetic retinopathy and AMD. These findings may provide a framework to support clinical studies, although further basic research is needed.

  12. Complex computation in the retina

    Deshmukh, Nikhil Rajiv

    Elucidating the general principles of computation in neural circuits is a difficult problem requiring both a tractable model circuit as well as sophisticated measurement tools. This thesis advances our understanding of complex computation in the salamander retina and its underlying circuitry and furthers the development of advanced tools to enable detailed study of neural circuits. The retina provides an ideal model system for neural circuits in general because it is capable of producing complex representations of the visual scene, and both its inputs and outputs are accessible to the experimenter. Chapter 2 describes the biophysical mechanisms that give rise to the omitted stimulus response in retinal ganglion cells described in Schwartz et al., (2007) and Schwartz and Berry, (2008). The extra response to omitted flashes is generated at the input to bipolar cells, and is separable from the characteristic latency shift of the OSR apparent in ganglion cells, which must occur downstream in the circuit. Chapter 3 characterizes the nonlinearities at the first synapse of the ON pathway in response to high contrast flashes and develops a phenomenological model that captures the effect of synaptic activation and intracellular signaling dynamics on flash responses. This work is the first attempt to model the dynamics of the poorly characterized mGluR6 transduction cascade unique to ON bipolar cells, and explains the second lobe of the biphasic flash response. Complementary to the study of neural circuits, recent advances in wafer-scale photolithography have made possible new devices to measure the electrical and mechanical properties of neurons. Chapter 4 reports a novel piezoelectric sensor that facilitates the simultaneous measurement of electrical and mechanical signals in neural tissue. This technology could reveal the relationship between the electrical activity of neurons and their local mechanical environment, which is critical to the study of mechanoreceptors

  13. Effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic reti-nopathy rats%臭氧治疗对糖尿病视网膜病变大鼠视网膜组织中细胞凋亡、血管新生的影响



    Objective:To study the effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats.Methods:SD rats were selected as experimental animals and divided into control group,model group and o-zone group,and after diabetic models were built,ozone enema was conducted.Retina tissue was collected,TUNEL kits were used to detect the number of apoptotic cells,and Elisa kits were used to detect the contents of nerve damage molecules,angio-genesis-related molecules and endoplasmic reticulum stress molecules.Results:The number of apoptotic cells in retina tissue of model group was significantly more than that of control group,and the number of apoptotic cells in retina tissue of ozone group was significantly less than that of model group;NgR,NR2B,ERK1,ERK2,GFAP,VEGF,STAT-3,HIF-1α,Apelin, APJ,PERK,IRE-1α,ATF-6,eIF2αand XBP-1 contents in retina tissue of model group were significantly higher than those of control group,and PEDF content was lower than that of control group;NgR,NR2B,ERK1,ERK2,GFAP,VEGF,STAT-3,HIF-1α,Apelin,APJ,PERK,IRE-1α,ATF-6,eIF2αand XBP-1 contents in retina tissue of ozone group were significantly lower than those of model group,and PEDF content was higher than that of model group.Conclusions:Ozone therapy can re-duce the number of apoptotic cells while reduce nerve cell injury and inhibit angiogenesis and endoplasmic reticulum stress in retina tissue of diabetic rats.%目的::研究臭氧治疗对糖尿病视网膜病变大鼠视网膜组织中细胞凋亡、血管新生的影响.方法:选择 SD 大鼠作为实验动物,分为对照组、模型组和臭氧组,建立糖尿病模型后给予臭氧灌肠.取视网膜组织并采用 TUNEL 试剂盒测定凋亡细胞数目,采用 Elisa 试剂盒测定神经损伤分子、血管新生相关分子、内质网应激分子的含量.结果:模型组大鼠视网膜组织中的凋亡细胞数目显著多于对照组,臭氧组大鼠视网膜组织中的凋亡细

  14. Is adding a new class of cones to the retina sufficient to cure color-blindness?

    Cornelissen, Frans W.; Brenner, Eli


    New genetic methods have made it possible to substitute cone pigments in the retinas of adult nonhuman primates. Doing so influences the animals' visual abilities, demonstrating that the gene therapy was effective. However, we argue that no studies conducted so far have unambiguously demonstrated

  15. Is adding a new class of cones to the retina sufficient to cure color-blindness?

    Cornelissen, Frans W.; Brenner, Eli


    New genetic methods have made it possible to substitute cone pigments in the retinas of adult nonhuman primates. Doing so influences the animals' visual abilities, demonstrating that the gene therapy was effective. However, we argue that no studies conducted so far have unambiguously demonstrated th

  16. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism.

    Rowlands, Benjamin D; Lau, Chew Ling; Ryall, James G; Thomas, Donald S; Klugmann, Matthias; Beart, Philip M; Rae, Caroline D


    Silent information regulators (SIRTs) have been shown to deacetylate a range of metabolic enzymes, including those in glycolysis and the Krebs cycle, and thus alter their activity. SIRTs require NAD(+) for their activity, linking cellular energy status to enzyme activity. To examine the impact of SIRT1 modulation on oxidative metabolism, this study tests the effect of ligands that are either SIRT-activating compounds (resveratrol and SRT1720) or SIRT inhibitors (EX527) on the metabolism of (13)C-enriched substrates by guinea pig brain cortical tissue slices with (13)C and (1)H nuclear magnetic resonance spectroscopy. Resveratrol increased lactate labeling but decreased incorporation of (13)C into Krebs cycle intermediates, consistent with effects on AMPK and inhibition of the F0/F1-ATPase. By testing with resveratrol that was directly applied to astrocytes with a Seahorse analyzer, increased glycolytic shift and increased mitochondrial proton leak resulting from interactions of resveratrol with the mitochondrial electron transport chain were revealed. SRT1720, by contrast, stimulated incorporation of (13)C into Krebs cycle intermediates and reduced incorporation into lactate, although the inhibitor EX527 paradoxically also increased Krebs cycle (13)C incorporation. In summary, the various SIRT1 modulators show distinct acute effects on oxidative metabolism. The strong effects of resveratrol on the mitochondrial respiratory chain and on glycolysis suggest that caution should be used in attempts to increase bioavailability of this compound in the CNS.

  17. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.


    Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

  18. A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers.

    Vincenzo Libri

    Full Text Available BACKGROUND: SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD(+-dependent deacetylase involved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucose metabolism, oxidative stress and lipid metabolism. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. We report the first clinical trial of SRT2104 in elderly volunteers. METHODS: Oral doses of 0.5 or 2.0 g SRT2104 or matching placebo were administered once daily for 28 days. Pharmacokinetic samples were collected through 24 hours post-dose on days 1 and 28. Multiple pharmacodynamic endpoints were explored with oral glucose tolerance tests (OGTT, serum lipid profiles, magnetic resonance imaging (MRI for assessment of whole body visceral and subcutaneous fat, maximal aerobic capacity test and muscle 31P magnetic resonance spectroscopy (MRS for estimation of mitochondrial oxidative capacity. RESULTS: SRT2104 was generally safe and well tolerated. Pharmacokinetic exposure increased less than dose-proportionally. Mean Tmax was 2-4 hours with elimination half-life of 15-20 hours. Serum cholesterol, LDL levels and triglycerides decreased with treatment. No significant changes in OGTT responses were observed. 31P MRS showed trends for more rapid calculated adenosine diphosphate (ADP and phosphocreatine (PCr recoveries after exercise, consistent with increased mitochondrial oxidative phosphorylation. CONCLUSIONS: SRT2104 can be safely administered in elderly individuals and has biological effects in humans that are consistent with SIRT1 activation. The results of this study support further development of SRT2104 and may be useful in dose selection for future clinical trials in patients. TRIAL REGISTRATION: NCT00964340.

  19. Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments.

    Zheng, Wenchao; Mast, Natalia; Saadane, Aicha; Pikuleva, Irina A


    Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholesterol content in the retina and had no significant effect on retinal expression of the major cholesterol- and vision-related genes; the sterol-regulatory element binding protein pathway of transcriptional regulation does not seem to be operative in the retina under the experimental conditions used. Evidence is obtained that posttranslational mechanisms play a role in the control of retinal cholesterol. Retinal genes were only upregulated by oral administrations of TO901317 activating liver X receptors. Three of the upregulated genes could be of particular importance (apoD, Idol, and Rpe65) and have not yet been considered in the context of cholesterol homeostasis in the retina. Collectively, the data obtained identify specific features of retinal cholesterol maintenance and suggest additional therapies for age-related macular degeneration, a blinding disease characterized by cholesterol and lipid accumulations in chorioretinal tissues.

  20. Chondroitin sulfate proteoglycans and microglia prevent migration and integration of grafted Müller stem cells into degenerating retina.

    Singhal, Shweta; Lawrence, Jean M; Bhatia, Bhairavi; Ellis, James S; Kwan, Anthony S; Macneil, Angus; Luthert, Philip J; Fawcett, James W; Perez, Maria-Thereza; Khaw, Peng T; Limb, G Astrid


    At present, there are severe limitations to the successful migration and integration of stem cells transplanted into the degenerated retina to restore visual function. This study investigated the potential role of chondroitin sulfate proteoglycans (CSPGs) and microglia in the migration of human Müller glia with neural stem cell characteristics following subretinal injection into the Lister hooded (LH) and Royal College of Surgeons (RCS) rat retinae. Neonate LH rat retina showed minimal baseline microglial accumulation (CD68-positive cells) that increased significantly 2 weeks after transplantation (p cell layer (GCL) and inner plexiform layer. In contrast, nontransplanted 5-week-old RCS rat retina showed considerable baseline microglial accumulation in the outer nuclear layer (ONL) and photoreceptor outer segment debris zone (DZ) that further increased (p retina 2 weeks after transplantation. Marked deposition of the N-terminal fragment of CSPGs, as well as neurocan and versican, was observed in the DZ of 5-week-old RCS rat retinae, which contrasted with the limited expression of these proteins in the GCL of the adult and neonate LH rat retinae. Staining for CSPGs and CD68 revealed colocalization of these two molecules in cells infiltrating the ONL and DZ of the degenerating RCS rat retina. Enhanced immune suppression with oral prednisolone and intraperitoneal injections of indomethacin caused a reduction in the number of microglia but did not facilitate Müller stem cell migration. However, injection of cells with chondroitinase ABC combined with enhanced immune suppression caused a dramatic increase in the migration of Müller stem cells into all the retinal cell layers. These observations suggest that both microglia and CSPGs constitute a barrier for stem cell migration following transplantation into experimental models of retinal degeneration and that control of matrix deposition and the innate microglial response to neural retina degeneration may need to be

  1. 腹腔注射SRT1720对慢性坐骨神经结扎大鼠痛觉敏化和脊髓Sirt1表达/活性的影响%Effect of intraperitoneal injection of SRT1720 on nociceptor sensitization and expression and activity of Sirt1 in spinal cord of rats with chronic sciatic nerve constriction injury

    吕晨; 郭小文; 郑晖; 叶玲; 马千; 张娟


    目的 观察腹腔注射SRT1720对慢性坐骨神经结扎大鼠痛觉敏化和脊髓Sirt1表达/活性的影响.方法 将96只SD大鼠随机分为6组:空白对照组(N组)、假手术组(Sham组)、坐骨神经慢性压迫损伤组(CCI组)、CCI+生理盐水注射组(CCI+ NS组)、CCI+低剂量SRT1720(SRT1720 20 mg/kg腹腔注射)、CCI+高剂量组(SRT1720 50 mg/kg腹腔注射).CCI模型建立后,分别通过微量注射器进行腹腔内注射2.5 ml/kg NS、20 mg/kgSRT1720、50 mg/g SRT1720,连续7d.各组分别在术前和术后第1、3、5、7、10、14天用von Frey细丝测定大鼠的机械性缩足反射阈值(MWT)和热辐射法测定大鼠的热缩足潜伏期(TWL),手术结束后提取大鼠脊髓测定Sirt1蛋白表达和去乙酰化酶活性.结果 SRT720能抑制大鼠机械性缩足反射阈值和热缩足潜伏期,浓度越高,抑制越明显(P <0.05);SRT720能增加脊髓背角Sirt1蛋白表达,浓度越高,增加越明显(P<0.05);SRT720能增加脊髓背角Sirt1去乙酰化酶活性,浓度越高,增加越明显(P<0.05).结论 腹腔注射SRT1720能抑制CCI大鼠的机械痛敏和热痛敏,其作用可能和增加脊髓Sirt1表达/活性有关.

  2. Crystallization and preliminary X-ray diffraction analysis of levansucrase (LsdA) from Gluconacetobacter diazotrophicus SRT4.

    Martínez-Fleites, Carlos; Tarbouriech, Nicolas; Ortiz-Lombardia, Miguel; Taylor, Edward; Rodríguez, Armando; Ramírez, Ricardo; Hernández, Lázaro; Davies, Gideon J


    The endophytic bacterium Gluconacetobacter diazotrophicus SRT4 secretes a constitutively expressed levansucrase (LsdA; EC, which converts sucrose to fructo-oligosaccharides and levan. Fully active LsdA was purified to high homogeneity by non-denaturing reversed-phase HPLC and was crystallized at room temperature by the hanging-drop vapour-diffusion method using ammonium sulfate and ethanol as precipitants. The crystals are extremely sensitive, but native data have been collected to 2.5 A under cryogenic conditions using synchrotron radiation. LsdA crystals belong to the orthorhombic space group P22(1)2(1) or P2(1)2(1)2, with unit-cell parameters a = 53.80, b = 119.39, c = 215.10 A.

  3. Removal of nitrogen and phosphorus in a combined A2/O-BAF system with a short aerobic SRT

    DING Yong-wei; WANG Lin; WANG Bao-zhen; WANG Zheng


    A bench-scale anaerobic/anoxic/aerobic process-biological aerated filter (A2/O-BAF) combined system was carried out to treat wastewater with lower C/N and C/P ratios. The A2/O process was operated in a short aerobic sludge retention time (SRT) for organic pollutants and phosphorus removal, and denitrification. The subsequent BAF process was mainly used for nitrification. The BAF effluent was partially returned to anoxic zone of the A2/O process to provide electron acceptors for denitrification and anoxic P uptake. This unique system formed an environment for reproducing the denitrifying phosphate-accumulating organisms (DPAOs). The ratio of DPAOs to phosphorus accumulating organisms (PAOs) could be maintained at 28% by optimizing the organic loads in the anaerobic zone and the nitrate loads into the anoxic zone in the A2/O process. The aerobic phosphorus over-uptake and discharge of excess activated sludge was the main mechanism of phosphorus removal in the combined system. The aerobic SRT of the A2/O process should meet the demands for the development of aerobic PAOs and the restraint on the nitrifiers growth, and the contact time in the aerobic zone of the A2/O process should be longer than 30 min, which ensured efficient phosphorus removal in the combined system. The adequate BAF effluent retum rates should be controlled with 1-4 mg/L nitrate nitrogen in the anoxic zone effluent of A2/O process to achieve the optimal nitrogen and phosphorus removal efficiencies.

  4. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W


    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  5. Macroglia-Microglia Interactions via TSPO Signaling Regulates Microglial Activation in the Mouse Retina

    Wang, Minhua; Wang, Xu; Zhao, Lian; Ma, Wenxin; Rodriguez, Ignacio R.; Fariss, Robert N.


    Chronic retinal inflammation in the form of activated microglia and macrophages are implicated in the etiology of neurodegenerative diseases of the retina, including age-related macular degeneration, diabetic retinopathy, and glaucoma. However, molecular biomarkers and targeted therapies for immune cell activation in these disorders are currently lacking. To address this, we investigated the involvement and role of translocator protein (TSPO), a biomarker of microglial and astrocyte gliosis in brain degeneration, in the context of retinal inflammation. Here, we find that TSPO is acutely and specifically upregulated in retinal microglia in separate mouse models of retinal inflammation and injury. Concomitantly, its endogenous ligand, diazepam-binding inhibitor (DBI), is upregulated in the macroglia of the mouse retina such as astrocytes and Müller cells. In addition, we discover that TSPO-mediated signaling in microglia via DBI-derived ligands negatively regulates features of microglial activation, including reactive oxygen species production, TNF-α expression and secretion, and microglial proliferation. The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence. Our results indicate that TSPO is a promising molecular marker for imaging inflammatory cell activation in the retina and highlight DBI-TSPO signaling as a potential target for immodulatory therapies. PMID:24599476

  6. An experimental platform for systemic drug delivery to the retina.

    Campbell, Matthew


    Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-\\/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

  7. Measuring cognitive factors in speech comprehension: the value of using the text reception threshold test as a visual equivalent of the SRT test

    Kramer, S.E.; Zekveld, A.A.; Houtgast, T.


    The ability to comprehend speech in noise is influenced by bottom-up auditory and top-down cognitive capacities. Separate examination of these capacities is relevant for various purposes. Speech-Reception-Threshold (SRT) tests measure an individual's ability to comprehend speech. This paper addresse

  8. Virtual screening of LPXTG competitive SrtA inhibitors targeting signal transduction mechanism in Bacillus anthracis: a combined experimental and theoretical study.

    Selvaraj, Chandrabose; Sivakamavalli, Jeyachandran; Baskaralingam, Vaseeharan; Singh, Sanjeev Kumar


    Members of the sortase enzyme super family decorate the surfaces of Bacillus anthracis cell wall with proteins that play key roles in microbial pathogenesis and its biofilm formation. Bacillus anthracis Sortase-A (Ba-SrtA) is a potential target for new therapeutics as it is required for B. anthracis survival and replication within macrophages. An understanding of the binding site pocket and substrate recognition mechanism by SrtA enzymes may serve to be beneficial in the rational development of sortase inhibitors. Here, the LPXTG signal peptide-based competitive inhibitors are screened against the Ba-SrtA and compounds with reasonable inhibition, specificity, and mechanisms of inactivation of SrtA have been covered. The screened compounds are experimentally validated against the phylogenetically similar Gram-positive pathogen B. cereus. In situ microscopic visualizations suggest that these screened compounds showed the microbial and biofilm inhibitory activity against B. cereus. It facilitates the further development of these molecules into useful anti-infective agents to treat infections caused by B. anthracis and other Gram-positive pathogens. These results provide insight into basic design principles for generating new clinically relevant lead molecules. It also provides an alternative strategy where a screened ligand molecule can be used in combination to battle increasingly against the Gram-positive pathogens.

  9. The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE{sup −/−} mice through inhibiting vascular inflammatory response

    Chen, Yi xi; Zhang, Man; Cai, Yuehua; Zhao, Qihui; Dai, Wenjian, E-mail:


    Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective. - Highlights: • SRT1720 reduced atherosclerotic lesion size in aortic arches and atherosclerotic lesion macrophage content. • SRT1720 could inhibit the phosphorylation of STAT3 and p65 phosphorylation and translocation. • SRT1720 could inhibit the expression of proinflammatory factor.

  10. Can we grow new retina?

    Geeta K Vemuganti


    Full Text Available Introduction Retinal degenerations and dystrophies, the major causes of genetically inherited blindness, are characterised by the death or degeneration of photoreceptors (rods and/or cones.1 Approaches to treating this disease include: a replacing the defective gene; b introducing a drug or agent that either slows down or stops the premature death of photoreceptors; c introducing electronic chips; or d replacing the damaged cells by cellular therapy. Gene therapy is aimed at counteracting the defective gene by substituting it with the normal gene in the target tissues. Though successful visual recovery has been reported with gene therapy in dog models,2-3 it remains a challenge to identify a safe and reliable way of introducing the corrective gene in humans, given that the genes need to act for the lifetime of the patient. Introduction of ‘a’ factors (such as growth factors into the eye, directly or through implants, is another novel approach to preventing or slowing premature cell death.4-5 The challenge lies in delivering the drug to the appropriate site in a safe and sustained manner. Electronic chips, similar to the ones used for audio aids, have shown exciting results in some studies, but the technology is still in its infancy.6-7

  11. Ultraviolet colour opponency in the turtle retina.

    Ventura, D F; Zana, Y; de Souza, J M; DeVoe, R D


    We have examined the functional architecture of the turtle Pseudemys scripta elegans retina with respect to colour processing, extending spectral stimulation into the ultraviolet, which has not been studied previously in the inner retina. We addressed two questions. (i) Is it possible to deduce the ultraviolet cone spectral sensitivity function through horizontal cell responses? (ii) Is there evidence for tetrachromatic neural mechanisms, i.e. UV/S response opponency? Using a constant response methodology we have isolated the ultraviolet cone input into the S/LM horizontal cell type and described it in fine detail. Monophasic (luminosity), biphasic L/M (red-green) and triphasic S/LM (yellow-blue) horizontal cells responded strongly to ultraviolet light. The blue-adapted spectral sensitivity function of a S/LM cell peaked in the ultraviolet and could be fitted to a porphyropsin cone template with a peak at 372 nm. In the inner retina eight different combinations of spectral opponency were found in the centre of the receptive field of ganglion cells. Among amacrine cells the only types found were UVSM-L+ and its reverse. One amacrine and four ganglion cells were also opponent in the receptive field surround. UV/S opponency, seen in three different types of ganglion cell, provides a neural basis for discrimination of ultraviolet colours. In conclusion, the results strongly suggest that there is an ultraviolet channel and a neural basis for tetrachromacy in the turtle retina.

  12. Vascular tumors of the choroid and retina

    Shanmugam, P Mahesh; Ramanjulu, Rajesh


    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  13. Lactate Transport and Receptor Actions in Retina

    Kolko, Miriam; Vosborg, Fia; Henriksen, Jens Ulrik Lütken;


    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also ...

  14. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina

    ZHOU Xue-mei; YUAN Hui-ping; WU Dong-lai; ZHOU Xin-rong; SUN Da-wei; LI Hong-yi; SHAO Zheng-bo


    Background Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. Methods NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. Results NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P<0.05) and at protein level measured by ELISA (P<0.05), which showed that BDNF was overexpressed in BDNF-NSCs. The results of HRA demonstrated that graft cells could survive well and migrate into the host retinas, while the immunohistochemical analysis revealed that transplanted BDNF-NSCs differentiated into neuron more efficiently compared with the control NSCs 2 months after transplantation. Conclusions The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in

  15. Changes in metabolic proteins in ex vivo rat retina during glutamate-induced neural progenitor cell induction.

    Tokuda, Kazuhiro; Kuramitsu, Yasuhiro; Baron, Byron; Kitagawa, Takao; Tokuda, Nobuko; Kobayashi, Masaaki; Kimura, Kazuhiro; Sonoda, Koh-Hei; Nakamura, Kazuyuki


    Understanding how energy metabolism and related proteins influence neural progenitor cells in adult tissues is critical for developing new strategies in clinical tissue regeneration therapy. We have recently reported that a subtoxic concentration of glutamate-induced neural progenitor cells in the mature ex vivo rat retina. We herein explore changes in the metabolic pathways during the process. We firstly observed an increase in lactate and lactate dehydrogenase concentration in the glutamate-treated retina. We then investigated the levels of glycolytic enzymes and confirmed significant upregulation of pyruvate kinase M type (PKM), especially PKM2, enolase, phosphoglycerate mutase 1 (PGAM1), and inosine-5'-monophosphate dehydrogenase (IMPDH1) in the glutamate-treated retina compared to the untreated retina. An analysis of the subcellular localization of PKM2 revealed nuclear translocation in the treated retina, which has been reported to regulate cell cycle proliferation and glycolytic enzymes. Our findings indicate that the mature rat retina undergoes an increase in aerobic glycolysis. PKM2, both in the cytoplasm and in the nucleus, may thus play an important role during neural progenitor cell induction, as it does in other proliferating cells.

  16. Using Stem Cells to Model Diseases of the Outer Retina

    Camille Yvon


    Full Text Available Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE. It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP, Usher syndrome (USH, Leber congenital amaurosis (LCA, gyrate atrophy (GA, juvenile neuronal ceroid lipofuscinosis (NCL, Best vitelliform macular dystrophy (BVMD and age related macular degeneration (AMD.

  17. BMP signaling mediates stem/progenitor cell-induced retina regeneration.

    Haynes, Tracy; Gutierrez, Christian; Aycinena, Juan-Carlos; Tsonis, Panagiotis A; Del Rio-Tsonis, Katia


    We identified a mechanism whereby retina regeneration in the embryonic chick can be induced by the contribution of stem/progenitor cells. We show that bone morphogenetic protein (BMP) signaling is sufficient and necessary to induce retina regeneration and that its action can be divided into two phases. By 3 days after postretinectomy (d PR), the BMP pathway directs proliferation and regeneration through the activation of Smad (canonical BMP pathway) and the up-regulation of FGF signaling by the MAPK pathway. By 7d PR, it induces apoptosis by activating p38 (a noncanonical BMP pathway) and down-regulating FGF signaling (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented, and BMP-induced regeneration can be further induced by inhibition of p38. These results unravel a mechanism for stem/progenitor cell-mediated retina regeneration, where BMP activation establishes a cross-talk with the FGF pathway and selectively activates the canonical and noncanonical BMP pathways. Retina stem/progenitor cells exist in other species, including humans. Thus, our findings provide insights on how retinal stem cells can be activated for possible regenerative therapies.

  18. Recruitment of stem cells into the injured retina after laser injury.

    Singh, Tajinder; Prabhakar, Sudesh; Gupta, Amod; Anand, Akshay


    Retinal degeneration is a devastating complication of diabetes and other disorders. Stem cell therapy for retinal degeneration has shown encouraging results but functional regeneration has not been yet achieved. Our study was undertaken to evaluate the localization of stem cells delivered to the retina by intravenous versus intravitreal infusion, because stem cell localization is a key factor in ultimate in vivo function. We used lineage-negative bone marrow-derived stem cells in a model wherein retina of mice was induced by precise and reproducible laser injury. Lin(-ve) bone marrow cells (BMCs) were labeled with a tracking dye and their homing capacity was analyzed at time points after infusion. We found that Lin(-ve) BMCs get incorporated into laser-injured retina when transplanted through either the intravitreal or intravenous route. The intravenous route resulted in optimal localization of donor cells at the site of injury. These cells incorporated into injured retina in a dose-dependent manner. The data presented in this study reflect the importance of dose and route for stem cell-based treatment designed to result in retinal regeneration.

  19. WE-F-304-03: Optic Nerve/Chiasm Hypofractionated SRS/SRT Dose Tolerance

    Milano, M. [University of Rochester Medical Center (United States)


    Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT’s work for cranial sites, and recurrent head and neck cancer. From literature-based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear-quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer-reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes. 1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60. Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear-quadratic model

  20. Silicon retina for optical tracking systems

    Strohbehn, K.; Jenkins, R. E.; Sun, X.; Andreou, A. G.


    There are a host of position sensors, such as quadcells and CCD's, which are candidates for detecting optical position errors and providing error signals for a mirror positioning loop. We are developing a novel, very high bandwidth, biologically inspired position sensor for optical position tracking systems. We present recent test results and design issues for the use of biologically inspired silicon retinas for spaceborne optical position tracking systems.

  1. TRPM3 expression in mouse retina.

    R Lane Brown

    Full Text Available Transient receptor potential (TRP channels constitute a large family of cation permeable ion channels that serve crucial functions in sensory systems by transducing environmental changes into cellular voltage and calcium signals. Within the retina, two closely related members of the melastatin TRP family, TRPM1 and TRPM3, are highly expressed. TRPM1 has been shown to be required for the depolarizing response to light of ON-bipolar cells, but the role of TRPM3 in the retina is unknown. Immunohistochemical staining of mouse retina with an antibody directed against the C-terminus of TRPM3 labeled the inner plexiform layer (IPL and a subset of cells in the ganglion cell layer. Within the IPL, TRPM3 immunofluorescence was markedly stronger in the OFF sublamina than in the ON sublamina. Electroretinogram recordings showed that the scotopic and photopic a- and b-waves of TRPM3(-/- mice are normal indicating that TRPM3 does not play a major role in visual processing in the outer retina. TRPM3 activity was measured by calcium imaging and patch-clamp recording of immunopurified retinal ganglion cells. Application of the TRPM3 agonist, pregnenolone sulfate (PS, stimulated increases in intracellular calcium in ~40% of cells from wild type and TRPM1(‑/‑ mice, and the PS-stimulated increases in calcium were blocked by co-application of mefenamic acid, a TRPM3 antagonist. No PS-stimulated changes in fluorescence were observed in ganglion cells from TRPM3(-/- mice. Similarly, PS-stimulated currents that could be blocked by mefenamic acid were recorded from wild type retinal ganglion cells but were absent in ganglion cells from TRPM3-/- mice.

  2. Connecting the Retina to the Brain

    Lynda Erskine


    Full Text Available The visual system is beautifully crafted to transmit information of the external world to visual processing and cognitive centers in the brain. For visual information to be relayed to the brain, a series of axon pathfinding events must take place to ensure that the axons of retinal ganglion cells, the only neuronal cell type in the retina that sends axons out of the retina, find their way out of the eye to connect with targets in the brain. In the past few decades, the power of molecular and genetic tools, including the generation of genetically manipulated mouse lines, have multiplied our knowledge about the molecular mechanisms involved in the sculpting of the visual system. Here, we review major advances in our understanding of the mechanisms controlling the differentiation of RGCs, guidance of their axons from the retina to the primary visual centers, and the refinement processes essential for the establishment of topographic maps and eye-specific axon segregation. Human disorders, such as albinism and achiasmia, that impair RGC axon growth and guidance and, thus, the establishment of a fully functioning visual system will also be discussed.

  3. The mammalian retina as a clock

    Tosini, Gianluca; Fukuhara, Chiaki


    Many physiological, cellular, and biochemical parameters in the retina of vertebrates show daily rhythms that, in many cases, also persist under constant conditions. This demonstrates that they are driven by a circadian pacemaker. The presence of an autonomous circadian clock in the retina of vertebrates was first demonstrated in Xenopus laevis and then, several years later, in mammals. In X. laevis and in chicken, the retinal circadian pacemaker has been localized in the photoreceptor layer, whereas in mammals, such information is not yet available. Recent advances in molecular techniques have led to the identification of a group of genes that are believed to constitute the molecular core of the circadian clock. These genes are expressed in the retina, although with a slightly different 24-h profile from that observed in the central circadian pacemaker. This result suggests that some difference (at the molecular level) may exist between the retinal clock and the clock located in the suprachiasmatic nuclei of hypothalamus. The present review will focus on the current knowledge of the retinal rhythmicity and the mechanisms responsible for its control.

  4. Decalcified choroidal osteoma found in the retina

    Yoshikawa T


    Full Text Available Tadanobu Yoshikawa, Kanji TakahashiDepartment of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, JapanAbstract: Choroidal osteoma is a benign tumor of the choroid. Herein, we report a rare case of decalcified choroidal osteoma found in the retina. A 27-year-old woman presented with visual loss. Her best-corrected visual acuity was 20/50 OS. Ophthalmoscopy of the left eye revealed a yellow-white calcified region accompanied by a decalcified region of four disc diameters in size. After 6 years, spectral-domain optical coherence tomography showed a tumor projected strongly upwards from the choroid and partially through the retina with serous retinal detachment, with both a lamellar appearance and mound-like area. The calcified region became more contractive than was observed on the first visit. Conversely, the decalcified region was wider than was observed on the first visit. Her best-corrected visual acuity was 20/400 OS. Choroidal osteoma was worsened by progression of decalcification. The decalcified choroidal osteoma resulted in poor visual acuity, and projected strongly upward from the choroid and into the retina.Keywords: osteoma, decalcification, choroidal osteoma

  5. Effect of diabetes on glycogen metabolism in rat retina.

    Sánchez-Chávez, Gustavo; Hernández-Berrones, Jethro; Luna-Ulloa, Luis Bernardo; Coffe, Víctor; Salceda, Rocío


    Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation.

  6. Fgf19 is required for zebrafish lens and retina development.

    Nakayama, Yoshiaki; Miyake, Ayumi; Nakagawa, Yu; Mido, Tomotaka; Yoshikawa, Maya; Konishi, Morichika; Itoh, Nobuyuki


    Fgf signaling plays crucial roles in morphogenesis. Fgf19 is required for zebrafish forebrain development. Here, we examined the roles of Fgf19 in the formation of the lens and retina in zebrafish. Knockdown of Fgf19 caused a size reduction of the lens and the retina, failure of closure of the choroids fissure, and a progressive expansion of the retinal tissue to the midline of the forebrain. Fgf19 expressed in the nasal retina and lens was involved in cell survival but not cell proliferation during embryonic lens and retina development. Fgf19 was essential for the differentiation of lens fiber cells in the lens but not for the neuronal differentiation and lamination in the retina. Loss of nasal fate in the retina caused by the knockdown of Fgf19, expansion of nasal fate in the retina caused by the overexpression of Fgf19 and eye transplantation indicated that Fgf19 in the retina was crucial for the nasal-temporal patterning of the retina that is critical for the guidance of retinal ganglion cell axons. Knockdown of Fgf19 also caused incorrect axon pathfinding. The present findings indicate that Fgf19 positively regulates the patterning and growth of the retina, and the differentiation and growth of the lens in zebrafish.

  7. Proteomic interactions in the mouse vitreous-retina complex.

    Jessica M Skeie

    Full Text Available PURPOSE: Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina. METHODS: Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software. RESULTS: We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor. CONCLUSIONS: Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.

  8. Purification and characterization of extracellular lipase from a new strain: Pseudomonas aeruginosa SRT 9 Purificação e caracterização de uma lipase extracelular produzida por uma nova cepa: Pseudomonas aeruginosa SRT9

    Prita S. Borkar


    Full Text Available An extra cellular lipase was isolated and purified from the culture broth of Pseudomonas aeruginosa SRT 9 to apparent homogeneity using ammonium sulfate precipitation followed by chromatographic techniques on phenyl Sepharose CL- 4B and Mono Q HR 5/5 column, resulting in a purification factor of 98 fold with specific activity of 12307.8 U/mg. The molecular weight of the purified lipase was estimated by SDS-PAGE to be 29 kDa with isoelectric point of 4.5. Maximum lipase activity was observed in a wide range of temperature and pH values with optimum temperature of 55ºC and pH 6.9. The lipase preferably acted on triacylglycerols of long chain (C14-C16 fatty acids. The lipase was inhibited strongly by EDTA suggesting the enzyme might be metalloprotein. SDS and metal ions such as Hg2+, Zn2+, Cu2+, Ag2+ and Fe2+ decreased the lipase activity remarkedly. Its marked stability and activity in organic solvents suggest that this lipase is highly suitable as a biotechnological tool with a variety of applications including organo synthetic reactions and preparation of enantiomerically pure pharmaceuticals. The Km and Vmax value of the purified enzyme for triolein hydrolysis were calculated to be 1.11 mmol/L and 0.05 mmol/L/minrespectively.Uma lipase extracelular foi isolada e purificada a partir de um caldo de cultura de Pseudomonas aeruginosa SRT9 até homogeneidade visível empregando-se precipitação com sulfato de amônia, seguida de técnicas cromatográficas em colunas de fenil sefarose CL-4B e Mono Q HR 5/5, obtendo-se um fator de purificação de 98 vezes, e atividade especifica de 12307,8 U/mg. Por SDS_PAGE, estimou-se que o peso molecular da lipase purificada é 29kDa, com um ponto isoelétrico de 4,5. A lipase apresentou atividade máxima em uma ampla faixa de temperatura e pH, com ótimos a 55ºC e pH 6,9. A lípase foi mais ativa sobre triacilglicerois de cadeia longa (C14-C16. A lipase foi fortemente inibida por EDTA, o que sugere que a

  9. Assessment of the biological effect of hypocrellin B in photodynamic therapy system for retina and choroid%竹红菌乙素对视网膜和脉络膜光动力学治疗系统生物学效应的评定作用

    韩丽娜; 顾瑛; 刘凡光; 李晓松


    biological effect of domestic photosensitizer hypocrellin B (HB) PTD system on retina and choroid was accessed in our study, to explore the worthiness of further study on the prospect of HB in treating SMD.OBJECTIVE: To introduce an experimental system to perform PDT irradiation system, the determination of the photosensitivity of the photosensitizers in vitro and evaluation of the therapeutic effect of photosensitizers for the retina and choroids in vivo.DESIGN: An open trial.SETTING, MATERIALS and INTERVENTION: The trial was conducted in the Department of Laser Medicine, General Hospital of Chinese PLA. Establishment of irradiation system: a laser window was created at the slit lamp microscope, which connected with 532 nm-laser in order to make the laser and the irradiation light of the slit lamp microscope to arrive at the fundus oculi at the same time. The photosensitivity of the photosensitizer was determined primarily by Methyl-thialolyl-tetrasolium(MTT) and compared with that of BPD-MA. Using chinchilla rabbits as subjects, the system was testified by domestic photosensitizer hypocrellin B photodynamic therapy (HB-PDT), whose biological effects at the irradiated area of rabbit were evaluated by fundus observation, fluorescein angiography and light and electron microscopy examination to investigate the feasibility and reliability of our experimental system.MAIN OUTCOME MEASURES: The coupling efficiency between sbt lamp microscope and laser, in vitro photosensitivity of photosensitizer and their biological effects at the irradiated area.RESULTS: The output of the laser was stable and the coupling efficiency between the laser and laser window of the slit lamp microscope was about 60%. The photosensitivity of HB in vitro was similar to BPD-MA, and HB-PDT displayed selective therapeutic property presented by closure of the retinal and choroidal capillaries with less damage to surrounding normal retina.CONCLUSION: It is useful to decide if a new photosensitizer fit for

  10. Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics and pharmacodynamics

    Howells, L. M.; Berry, D P; P.J. Elliott; Jacobson, E. W.; Hoffmann, E; Hegarty, B.; Brown, K; Steward, W P; Gescher, A. J.


    The phytochemical resveratrol has undergone extensive preclinical investigation for its putative cancer chemopreventive properties. Low systemic availability of the parent compound due to rapid and extensive metabolism, may confound its usefulness as a potential agent to prevent malignancies in organs remote from the site of absorption. Micronization allows increased drug absorption, thus increasing availability. Here we describe a pilot study of SRT501, micronized resveratrol, given at 5.0 g...

  11. Using induced pluripotent stem cell-derived conditional medium to attenuate the light-induced photodamaged retina of rats

    Hua-Ming Chang


    Conclusion: The conditional medium of iPSCs contains plenty of cytoprotective, immune-modulative and rescue chemicals, contributing to the maintenance of neuronal function and retinal layers in light-damaged retina compared with apoptotic iPSC-CM and PBS. The antiapoptotic effect of iPSC-CM also shows promise in restoring damaged neurons. This result demonstrates that iPSC-CM may serve as an alternative to cell therapy alone to treat retinal light damage and maintain functional and structural integrity of the retina.

  12. Expression and functions of ASIC1 in the zebrafish retina.

    Liu, Sha; Wang, Mei-Xia; Mao, Cheng-Jie; Cheng, Xiao-Yu; Wang, Chen-Tao; Huang, Jian; Zhong, Zhao-Min; Hu, Wei-Dong; Wang, Fen; Hu, Li-Fang; Wang, Han; Liu, Chun-Feng


    It has been demonstrated that acid sensing ionic channels (ASICs) are present in the central and peripheral nervous system of mammals, including the retina. However, it remains unclear whether the zebrafish retina also expresses ASICs. In the present study, the expression and distribution of zasic1 were examined in the retina of zebrafish. Both zasic1 mRNA and protein expressions were detected in the adult zebrafish retina. A wide distribution of ASIC1 in zebrafish retina was confirmed using whole mount in situ hybridization and immunohistochemistry study. Acidosis-induced currents in the isolated retinal ganglion cells (RGCs) were also recorded using whole cell patch clamping. Moreover, blockade of ASICs channel significantly reduced the locomotion of larval zebrafish in response to light exposure. In sum, our data demonstrate the presence of ASIC1 and its possible functional relevance in the retina of zebrafish.


    王建明; 胡海涛; 马东亮; 孙乃学; 赵世平; 冯海晓


    Objective To investigate the distribution of brain-derived neurotrophic factor(BDNF) protein in the rabbit retina. Methods Immune response material in the retina was observed using BDNF antibody by the method of immunohistochemistry. Results BDNF gene expression was mainly found in the RGCs, also in innernuclei cells and outernuclei cells in rabbit retina. Conclusion RGC is not only the target cell of BDNF, but also express the BDNF protein. BDNF from multi-sources participates in the regulation of RGCs.

  14. Artificial Retina Project: Electromagnetic and Thermal Effects

    Lazzi, Gianluca


    This award supported the investigation on electromagnetic and thermal effects associated with the artificial retina, designed in collaboration with national laboratories, universities, and private companies. Our work over the two years of support under this award has focused mainly on 1) Design of new telemetry coils for optimal power and data transfer between the implant and the external device while achieving a significant size reduction with respect to currently used coils; 2) feasibility study of the virtual electrode configuration 3) study the effect of pulse shape and duration on the stimulation efficacy.

  15. The microglia in healthy and diseased retina.

    Li, Lu; Eter, Nicole; Heiduschka, Peter


    The microglia are the immune cells of the central nervous system and, also the retina. They fulfil several tasks of surveillance in the healthy retina. In case of an injury or disease, microglia become activated and tries to repair the damage. However, in a lot of cases it does not work, and microglia deteriorate the situation by releasing toxic and pro-inflammatory compounds. Moreover, they further promote degenerative processes by attacking and phagocytosing damaged neurones and photoreceptors that otherwise would possibly have the chance to survive. Such deleterious action of the microglia has been observed in degeneration of retinal ganglion cells and photoreceptors, and it takes place in hereditary diseases, infections as well as in case of traumatic or light injuries. Therefore, a number of attempts has been undertaken so far to inhibit the microglia, with varying success. The task remains to study behaviour of the microglia and their interaction with other retinal cell populations in more detail with respect to released factors and expressed receptors including the time points of the corresponding events. The goal has to be to find a better balance between helpful and detrimental actions of the microglia.

  16. Retina projection using curved lens arrays

    Yen, Hao-Ren; Su, Guo-Dung J.


    In this paper, we propose a multi-channel imaging system which combines the principles of an insect's compound eye and optical cluster eye. The system consists of two curved structure lens arrays with different pitches. Both of them have the same curvature and the radiuses of the lenses in the arrays are optimized to focus rays on the retina. The optical axes of different channels are tilted to each other in order to reduce the optical system volume and transmit a wide field of view. Each channel of an array of multiple optical system transfers only a part of the field of view. Each partial image passes through each channel and stitches together on the retina to reconstruct a complete image. In order to simulate the image stitching, we also build an eye model. The thickness from the panel to the last surface of lens group is less than 25mm. The panel size is designed to be 4 inch which is the scale of eyeglass. The system can provide a large field of view about 150 degrees which is much wider than the commercial products. By using the 3D printer, we can make a model of lens array to achieve our design.

  17. Ephaptic communication in the vertebrate retina

    Rozan eVroman


    Full Text Available In the vertebrate retina, cones project to the horizontal cells (HCs and bipolar cells (BCs. The communication between cones and horizontal cells uses both chemical and ephaptic mechanisms. Photoreceptors release glutamate in a Ca2+-dependent manner, while HCs feed back to cones via an ephaptic mechanism. Hyperpolarization of HCs leads to an increased current through connexin hemichannels located on the tips of HC dendrites invaginating the cone synaptic terminals. This current makes the extracellular synaptic space slightly negative. The result is that the Ca2+-channels in the cone pre-synaptic membrane experience a slightly depolarized membrane potential and therefore more glutamate is released. This ephaptic mechanism forms a very fast and noise free negative feedback pathway. These characteristics are crucial, since the retina has to perform well in demanding conditions such as low light levels and detecting fast events. In this mini-review we will discuss the critical components of such an ephaptic mechanism. Furthermore, we will address the question whether such communication appears in other systems as well and indicate some fundamental features to look for when attempting to identify an ephaptic mechanism.

  18. Association of tuberculosis with vasculitis retinae.

    Habibullah, M; Uddin, M S; Islam, S


    Retinal vasculitis is one of the common causes of blindness among the young adult in this subcontinent. Causes of retinal vasculitis are variable and it is one of the common ocular manifestations of tuberculosis. This case control study was carried out on 45 patients with retinal vasculitis of different age groups. All the patients were purposively selected from the department of ophthalmology, Bangabandhu Sheikh Mujib Medical University and National Institute of Ophthalmology Dhaka. This study reveals that vasculitis retinae is a disease of younger age group (68.9%). Mean+/-SD age of cases were 31.84+/-10.82 years. It occurs more in male (75.6%) and male female ratio is 3.09:1, single or both eye may involve. Retinal vasculitis occurs more in middle socio-economic status persons (62.2%). It present with floaters (58.9%), hazy media (60%), vitreous haemorrhage (57.8%) and retinal haemorrhage (42.2%). All 45 subjects both cases and control groups were tested with Mantoux test. 18(40%) subjects of cases and 13(28.9%) subjects of control group were found positive Mantoux test. It was observed that the association of tuberculosis with vasculitis retinae is not statistically significant. As tuberculosis is common in this country, further specific and extensive study over a longer period of time is necessary for understanding the role of tuberculosis in retinal vasculitis patients.

  19. Internet of Things for smart rail transportation: aiming for wider range of object-interconnection%智慧轨道交通全联网(SRT-IoT)——更广泛的互联互通

    窦军; 曾华燊; 谭献海; 张新有


    Taking rail transportation industry as the background, a framework of the "Internet of Things" for Smart Rail Transportation (SRT-IoT) was proposed and its key techniques were explored. With the perception of the next generation Internet, this framework was characterized by a Backbone Communication Network for SRT (SRT-BCN) interconnected by various Basic Access-Resource Networks (BARN) with clients and resource servers. Furthermore, rail-transportation specific BARNs were classified into two groups: Train-based Access-Resource Network (TARN) and Ground-based Access-Resource Network (GARN). Techniques feasible for different network were also analyzed in different details, and an emphasis had been given to TARN with a conclusion that TARN related network technologies should further develop as a research basis of SRT-IoT for wider interconnection.%以轨道交通行业为背景,以智慧轨道交通(SRT)为对象,研究智慧轨道交通“全联网”(IoT)的基本组成框架和关键技术.将IoT置于下一代Internet背景之中,提出了以“智慧轨道交通骨干通信网”(SRT-BCN)为核心、以“基础接入网-资源网络”为轨道交通信息源和受主网络的“智慧轨道交通全联网( IoT for SRT,SRT-IoT)”的系统组成框架.针对轨道交通行业的特点,进一步将智慧轨道交通基础接入—资源网中与轨道交通有关部分划分为“列车接入—资源网”(TARN)和“地面接入—资源网”(GARN),并分析智慧轨道交通骨干通信网(SRT-BCN)和外围接入/资源网的特点,讨论相关的关键技术.重点讨论了与列车相关的TARN技术,得出需要进一步发展TARN相关网络技术的结论,为实现SRT-IoT更广泛的互联互通奠定研究基础.

  20. Mutations in the Gene Encoding the Ancillary Pilin Subunit of the Streptococcus suis srtF Cluster Result in Pili Formed by the Major Subunit Only

    Fittipaldi, Nahuel; Takamatsu, Daisuke; la Cruz Domínguez-Punaro, María de; Lecours, Marie-Pier; Montpetit, Diane; Osaki, Makoto; Sekizaki, Tsutomu; Gottschalk, Marcelo


    Pili have been shown to contribute to the virulence of different Gram-positive pathogenic species. Among other critical steps of bacterial pathogenesis, these structures participate in adherence to host cells, colonization and systemic virulence. Recently, the presence of at least four discrete gene clusters encoding putative pili has been revealed in the major swine pathogen and emerging zoonotic agent Streptococcus suis. However, pili production by this species has not yet been demonstrated. In this study, we investigated the functionality of one of these pili clusters, known as the srtF pilus cluster, by the construction of mutant strains for each of the four genes of the cluster as well as by the generation of antibodies against the putative pilin subunits. Results revealed that the S. suis serotype 2 strain P1/7, as well as several other highly virulent invasive S. suis serotype 2 isolates express pili from this cluster. However, in most cases tested, and as a result of nonsense mutations at the 5′ end of the gene encoding the minor pilin subunit (a putative adhesin), pili were formed by the major pilin subunit only. We then evaluated the role these pili play in S. suis virulence. Abolishment of the expression of srtF cluster-encoded pili did not result in impaired interactions of S. suis with porcine brain microvascular endothelial cells. Furthermore, non-piliated mutants were as virulent as the wild type strain when evaluated in a murine model of S. suis sepsis. Our results show that srtF cluster-encoded, S. suis pili are atypical compared to other Gram-positive pili. In addition, since the highly virulent strains under investigation are unlikely to produce other pili, our results suggest that pili might be dispensable for critical steps of the S. suis pathogenesis of infection. PMID:20052283

  1. Designing and Implementation of Retina Image Drawing System and Automatic Report Generation from Retina Examinations

    Safdari, Reza; Mokhtaran, Mehrshad; Tahmasebian, Shahram


    Introduction: Electronic medical records as one of major parts of electronic health records is an important application of Medical Informatics. EMR includes different types of data, Graphical items being one of these data types. To this end, a standard structure for storing and recovering and finally exchanging this data type is required. In order to standardize information items in this research, UMLS standard is used. In this research, graphical information from fondues designing in retina surgery forms is used for the task of implementation. Implementation: Three-layer software architecture is used for implementation of this system, which includes user interface, data base access and business logic. XML database is used for storing and exchanging of data. User interface is designed by the means of Adobe Flash. Also in the user interface for eye examinations, appropriate icons compatible with current pathologies in retina examinations are considered and UMLS codes are used for standardizations purposes. Results: As this project is independently implemented in Adobe Flash, it can be run in most of electronic patient records software. For evaluation purposes of this research, an EMR system for eye clinics is used. Tree structure is used for data entry and finally a text report based on the entered data will be generated. By storing graphical items in this software editing and searching in medical concepts and also comparing features will be available. Conclusion: One of the data items that we encounter in various medical records is graphical data. In order to cover the patient’s complete electronic medical records, the Electronic Implementation of this information is important. For this purpose, graphical items in retina surgery forms were used and finally a software application for drawing retina picture was developed. Also, XML files were used for the purpose of storing valuable medical data from the pictures, and also UMLS were applied for the standardization

  2. Adaptive optics imaging of the retina.

    Battu, Rajani; Dabir, Supriya; Khanna, Anjani; Kumar, Anupama Kiran; Roy, Abhijit Sinha


    Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) meetings. In total, 261 relevant publications and 389 conference abstracts were identified.

  3. Adaptive optics imaging of the retina

    Rajani Battu


    Full Text Available Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO and American Academy of Ophthalmology (AAO meetings. In total, 261 relevant publications and 389 conference abstracts were identified.

  4. Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors.

    Lotery, Andrew J; Derksen, Todd A; Russell, Stephen R; Mullins, Robert F; Sauter, Sybille; Affatigato, Louisa M; Stone, Edwin M; Davidson, Beverly L


    We hypothesize that recombinant feline immunodeficiency viral (rFIV) vectors may be useful for gene transfer to the nonhuman primate retina. We performed vitrectomies and subretinal injections in the right eyes of 11 cynomolgus monkeys. Vesicular stomatitis virus glycoprotein-pseudotyped rFIV that expressed the Escherichia coli beta-galactosidase gene was injected into eight eyes. Sham vehicle or lactose buffer injections were also performed in two of these eight study eyes. rFIV pseudotyped with an amphotropic envelope was used in two eyes, and in one animal injections of lactose buffer only were given. After surgery the animals were clinically evaluated by retinal photography and electroretinography. beta-Galactosidase expression was evaluated, at a final end point, in histological sections. We found photoreceptor and Müller cells to have the greatest transgene expression. Focal inflammatory responses localized to the injection site were seen histologically in all eyes. No difference in transduction efficiency was seen between injections near the macula and more peripheral injections. Visual function as assessed by electroretinography was not significantly affected by vector or vehicle injections. We conclude that rFIV vectors administered beneath the retina can transduce a variety of retinal cells in the nonhuman primate retina. rFIV vectors have therapeutic potential and could be exploited to develop gene therapy for the human eye.

  5. Phenotypic and functional characterization of Bst+/− mouse retina

    Hamidreza Riazifar


    Full Text Available The belly spot and tail (Bst+/− mouse phenotype is caused by mutations of the ribosomal protein L24 (Rpl24. Among various phenotypes in Bst+/− mice, the most interesting are its retinal abnormalities, consisting of delayed closure of choroid fissures, decreased ganglion cells and subretinal vascularization. We further characterized the Bst+/− mouse and investigated the underlying molecular mechanisms to assess the feasibility of using this strain as a model for stem cell therapy of retinal degenerative diseases due to retinal ganglion cell (RGC loss. We found that, although RGCs are significantly reduced in retinal ganglion cell layer in Bst+/− mouse, melanopsin+ RGCs, also called ipRGCs, appear to be unchanged. Pupillary light reflex was completely absent in Bst+/− mice but they had a normal circadian rhythm. In order to examine the pathological abnormalities in Bst+/− mice, we performed electron microscopy in RGC and found that mitochondria morphology was deformed, having irregular borders and lacking cristae. The complex activities of the mitochondrial electron transport chain were significantly decreased. Finally, for subretinal vascularization, we also found that angiogenesis is delayed in Bst+/− associated with delayed hyaloid regression. Characterization of Bst+/− retina suggests that the Bst+/− mouse strain could be a useful murine model. It might be used to explore further the pathogenesis and strategy of treatment of retinal degenerative diseases by employing stem cell technology.

  6. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

    Hickmott, Jack W; Chen, Chih-yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M


    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia. PMID:27556059

  7. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

    Jack W Hickmott


    Full Text Available Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6 gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

  8. Method to Remove Photoreceptors from Wholemount Retina in vitro.

    Walston, Steven T; Chang, Yao-Chuan; Weiland, James D; Chow, Robert H


    Patch clamp recordings of neurons in the inner nuclear layer of the retina are difficult to conduct in a wholemount retina preparation because surrounding neurons block the path of the patch pipette. Vertical slice preparations or dissociated retina cell cultures provide access to bipolar cells at the cost of severing lateral connection between neurons. We have developed a technique to remove photoreceptors from the rodent retina that exposes inner nuclear layer neurons, allowing access for patch clamp recording. Repeated application and removal of filter paper to the photoreceptor side of an isolated retina effectively and efficiently removes photoreceptor cells and, in degenerate retina, hypertrophied Müller cell endfeet. Live-dead assays applied to neurons remaining after photoreceptor removal demonstrated mostly viable cells. Patch clamp recordings from bipolar cells reveal responses similar to those recorded in traditional slice and dissociated cell preparations. An advantage of the photoreceptor peel technique is that it exposes inner retinal neurons in a wholemount retina preparation for investigation of signal processing. A disadvantage is that photoreceptor removal alters input to remaining retinal neurons. The technique may be useful for investigations of extracellular electrical stimulation, photoreceptor DNA analysis, and non-pharmacological removal of light input. Copyright © 2017, Journal of Neurophysiology.

  9. Fluorescence spectroscopy of the retina from scrapie-infected mice.

    Bose, Sayantan; Schönenbrücher, Holger; Richt, Jürgen A; Casey, Thomas A; Rasmussen, Mark A; Kehrli, Marcus E; Petrich, Jacob W


    Recently, we have proposed that the fluorescence spectra of sheep retina can be well correlated with the presence or absence of scrapie. Scrapie is the most widespread TSE (transmissible spongiform encephalopathy) affecting sheep and goats worldwide. Mice eyes have been previously reported as a model system to study age-related accumulation of lipofuscin, which has been investigated by monitoring the increasing fluorescence with age covering its entire life span. The current work aims at developing mice retina as a convenient model system to diagnose scrapie and other fatal TSE diseases in animals such as sheep and cows. The objective of the research reported here was to determine whether the spectral features are conserved between two different species namely mice and sheep, and whether an appropriate small animal model system could be identified for diagnosis of scrapie based on the fluorescence intensity in retina. The results were consistent with the previous reports on fluorescence studies of healthy and scrapie-infected retina of sheep. The fluorescence from the retinas of scrapie-infected sheep was significantly more intense and showed more heterogeneity than that from the retinas of uninfected mice. Although the structural characteristics of fluorescence spectra of scrapie-infected sheep and mice eyes are slightly different, more importantly, murine retinas reflect the enhancement of fluorescence intensity upon infecting the mice with scrapie, which is consistent with the observations in sheep eyes.

  10. Lipid nanoparticles as drug/gene delivery systems to the retina.

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles


    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

  11. Experiencing Effects of Cocaine and Speed with Self-Regulation Therapy.

    Amigó, Salvador; Ferrández, Claudia


    This study demonstrates the efficacy of Self-Regulation Therapy (SRT) to induce effects of cocaine and speed in a single session. SRT is a suggestion procedure of sensorial recall exercises (salivation, feeling of weight, tension, etc.) that increases the capacity to reproduce all sensation types and those that drugs produce. The Self-Regulation Scale (SRS) measures this capacity. Four groups participated, formed according to drug use: Group 1 (uses no illegal drugs); Group 2 (experimentally uses cannabis only); Group 3 (moderate drug users); Group 4 (regular drug users, especially stimulants). All four groups participated in an SRT session to induce relaxation. No differences in the SRS were found. Group 4 also participated in a session that reproduced effects of drugs with SRT, when Euphoria and the Effects of drugs score (high and rush) substantially increased in relation to the base-line (MD = -5.83; p < .001; and MD = -3; p < .001, respectively) and in relation to the relaxation session (MD = -4.06; p < .001; and MD = -1.96; p < .05, respectively). A profile predicting SRT efficacy was also obtained to induce the effects of cocaine and speed: low Conscientiousness and high Openness and SRS scores. Finally, the potential use of this procedure to treat addictions, and strategy development towards more controlled, responsible drug use, are discussed.

  12. Development of diabetes-induced acidosis in the rat retina.

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A


    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Adaptive optics optical coherence tomography for retina imaging

    Guohua Shi; Yun Dai; Ling Wang; Zhihua Ding; Xuejun Rao; Yudong Zhang


    When optical coherence tomography (OCT) is used for human retina imaging, its transverse resolution is limited by the aberrations of human eyes. To overcome this disadvantage, a high resolution imaging system for living human retina, which consists of a time domain OCT system and a 37-elements adaptive optics (AO) system, has been developed. The AO closed loop rate is 20 frames per second, and the OCT has a 6.7-μm axial resolution. In this paper, this system is introduced and the high resolution imaging results for retina are presented.

  14. Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder.

    Kyle, Simon D; Miller, Christopher B; Rogers, Zoe; Siriwardena, A Niroshan; Macmahon, Kenneth M; Espie, Colin A


    To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Within-subject, noncontrolled treatment investigation. Sleep research laboratory. Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ≤ 6 h. Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia.

  15. The risk of retina damage from high intensity light sources.

    Pollak, V A; Romanchuk, K G


    The risk of thermal damage to the retina of the eye by exposure to excessive light intensities from continuous and pulsed man-made sources is discussed. The probability of injury increases, the larger the radiant power absorbed by the retina and the smaller the size of the retinal image of the source. A mehtod of estimating the temperature increase of the immediately affected area of the retina is presented. The time constants involved are also briefly considered. Using numerical values from literature for the relevant parameters of the eye, threshold values for a variety of conditions can be established. Below these values little risk of retina damage should exist. The degree of hazard when these values are exceeded depends upon the circumstances. A case study of a welding accident showed good agreement between the conclusions of the theoretical analysis and clinical findings.

  16. Simple Experiments on the Physics of Vision: The Retina

    Cortel, Adolf


    Many simple experiments can be performed in the classroom to explore the physics of vision. Students can learn of the two types of receptive cells (rods and cones), their distribution on the retina and the existence of the blind spot.

  17. Pharmacology of the GABAB receptor in amphibian retina.

    Tian, N; Slaughter, M M


    Amacrine and ganglion cells in the amphibian retina contain GABAB, as well as GABAA, receptors. Baclofen, a GABAB agonist, hyperpolarizes the dark membrane potential of these third order neurons and makes their light responses more transient. GABAB receptors in the retina have a similar agonist profile to GABAB receptors described at other sites in the brain. Namely, preferential activation by the R-enantiomer of baclofen, and agonist sensitivity in the order 3-aminopropylphosphinic acid > baclofen > 3-aminopropylphosphonic acid. The GABAB receptor was not activated by 4-aminobutylphosphonic acid. Several antagonists, such as phaclofen, saclofen, and 2-hydroxysaclofen, were ineffective in the amphibian retina. However, CGP35348 blocked the action of applied baclofen and produced effects on the light response that were opposite to those of baclofen. Applied agonists and antagonists support the hypothesis that GABAB receptors serve to regulate the balance of sustained and transient signals to the inner retina.

  18. Light-evoked S-nitrosylation in the retina

    Tooker, Ryan E; Vigh, Jozsef


    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pre-treatment with NEM, which occludes S-nitrosylation, or with TRIM, an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina, light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant post-translational modification affecting a wide range of proteins under physiological conditions. PMID:25823749

  19. Light-evoked S-nitrosylation in the retina.

    Tooker, Ryan E; Vigh, Jozsef


    Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S-nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S-nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity-dependent manner, with a strikingly similar pattern in both species. Pretreatment with N-ethylmaleimide (NEM), which occludes S-nitrosylation, or with 1-(2-trifluromethylphenyl)imidazole (TRIM), an inhibitor of neuronal NO synthase, eliminated the light-evoked increase in S-nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light-adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S-nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina light-evoked NO production leads to extensive S-nitrosylation and that this process is a significant posttranslational modification affecting a wide range of proteins under physiological conditions.

  20. Glutamine synthetase localization in cortisol-induced chick embryo retinas


    We report here for the first time, in chick retina, Muller cell localization of glutamine synthetase (GS) activity by an immunohistochemical technique, in agreement with previous reports of glial localization of this enzyme in rat brain and retina. Age- dependent changes in the endogenous enzyme activity as well as cortisol- induced changes in GS activity, both in ovo and in vitro, measured biochemically, reflect the changes observed by staining.

  1. Comparison of dose distribution between hypofractionated IMRT and SRT plans in lung tumor%IMRT和SRT大分割治疗肺部肿瘤的剂量分布研究

    吴凤; 肖建平; 张可; 姜雪松; 宋一昕; 张红志; 李晔雄


    Objective To compare the characteristics of dose distribution between hypofractionated intensity modulated radiotherapy (IMRT) and hypofractionated stereotactic radiotherapy (SRT) plans in lung tumor and to select an optimal clinical approach. Methods SRT plans were designed for 16 patients with lung tumors who had received IMRT between April 2007 and April 2008. The dose distribution of target volume and normal tissues, conformal index (CI) and heteregenous index (HI) were analyzed using the dose-volume histogram (DVH) for the IMRT and SRT plans. Results The mean dose and equivalent uni-form dose of planning target volume (PTV) in IMRT were similar to those in SRT. SRT had significantly better CI and HI than IMRT (t = 2.77, P 0.05 ). The lung V20 of IMRT and SRT was 6.9% ± 2.1% and 4.2%± 1.9%, respectively ( t = 3.30, P 0.05),均一化剂量分别为6366.7 cGy和6246.8 cGy(t=-1.18,P>0.05),CI平均值分别为0.78和0.57(t=2.77,P0.05),全肺V20分别为6.9%±2.1%和4.2%±1.9%(t=3.30,P<0.01).IMRT和SRT计划的心脏和脊髓平均受照剂量无差别.结论 PTV最大径<4.7 cm、靶体积<57 cm3、靶区呈圆形或类圆形时,SRT靶区剂量与大分割IMRT接近并可满足临床要求;SRT计划正常肺组织受照剂量低于大分割IMRT计划.

  2. Efficient control structures for digital programmable retinas

    Bernard, Thierry M.


    A digital programmable artificial retina (PAR) is a functional extension of a CMOS imager, in which every pixel is fitted with a local ADC and a tiny digital programmable processor. From an architectural viewpoint, a PAR is an SIMD array processor with local optical input. A PAR is aimed at processing images on-site until they can be output from the array under concentrated form. The overall goal is to get compact, fast and inexpensive vision systems, in particular for robotics applications. A 256 by 256 PAR with up to a few tens bits of local memory per pixel is now within reach at reasonable cost. However, whereas the local memory size benefits quadratically from the feature size decrease, wiring density improvement can only be linear, at best. So control should become more complex with the danger of a growing proportion of the digital pixel area being devoted to instruction or address decoding. We propose efficient scalable solutions to this problem at the architectural, circuit and topological levels, which attempt to minimize both silicon area and power consumption.

  3. Transformation of stimulus correlations by the retina.

    Simmons, Kristina D; Prentice, Jason S; Tkačik, Gašper; Homann, Jan; Yee, Heather K; Palmer, Stephanie E; Nelson, Philip C; Balasubramanian, Vijay


    Redundancies and correlations in the responses of sensory neurons may seem to waste neural resources, but they can also carry cues about structured stimuli and may help the brain to correct for response errors. To investigate the effect of stimulus structure on redundancy in retina, we measured simultaneous responses from populations of retinal ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure; these stimuli and recordings are publicly available online. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were modestly more correlated than in response to white noise checkerboards, but they were much less correlated than predicted by a non-adapting functional model of retinal response. Meanwhile, responding to stimuli with purely spatial correlations, pairs of ganglion cells showed increased correlations consistent with a static, non-adapting receptive field and nonlinearity. We found that in response to spatio-temporally correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the pattern of pairwise correlations across stimuli where receptive field measurements were possible.

  4. Transformation of stimulus correlations by the retina.

    Kristina D Simmons

    Full Text Available Redundancies and correlations in the responses of sensory neurons may seem to waste neural resources, but they can also carry cues about structured stimuli and may help the brain to correct for response errors. To investigate the effect of stimulus structure on redundancy in retina, we measured simultaneous responses from populations of retinal ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure; these stimuli and recordings are publicly available online. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were modestly more correlated than in response to white noise checkerboards, but they were much less correlated than predicted by a non-adapting functional model of retinal response. Meanwhile, responding to stimuli with purely spatial correlations, pairs of ganglion cells showed increased correlations consistent with a static, non-adapting receptive field and nonlinearity. We found that in response to spatio-temporally correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the pattern of pairwise correlations across stimuli where receptive field measurements were possible.

  5. Monte Carlo simulation of zinc protoporphyrin fluorescence in the retina

    Chen, Xiaoyan; Lane, Stephen


    We have used Monte Carlo simulation of autofluorescence in the retina to determine that noninvasive detection of nutritional iron deficiency is possible. Nutritional iron deficiency (which leads to iron deficiency anemia) affects more than 2 billion people worldwide, and there is an urgent need for a simple, noninvasive diagnostic test. Zinc protoporphyrin (ZPP) is a fluorescent compound that accumulates in red blood cells and is used as a biomarker for nutritional iron deficiency. We developed a computational model of the eye, using parameters that were identified either by literature search, or by direct experimental measurement to test the possibility of detecting ZPP non-invasively in retina. By incorporating fluorescence into Steven Jacques' original code for multi-layered tissue, we performed Monte Carlo simulation of fluorescence in the retina and determined that if the beam is not focused on a blood vessel in a neural retina layer or if part of light is hitting the vessel, ZPP fluorescence will be 10-200 times higher than background lipofuscin fluorescence coming from the retinal pigment epithelium (RPE) layer directly below. In addition we found that if the light can be focused entirely onto a blood vessel in the neural retina layer, the fluorescence signal comes only from ZPP. The fluorescence from layers below in this second situation does not contribute to the signal. Therefore, the possibility that a device could potentially be built and detect ZPP fluorescence in retina looks very promising.

  6. Gene Transcription Profile of the Detached Retina (An AOS Thesis)

    Zacks, David N.


    Purpose: Separation of the neurosensory retina from the retinal pigment epithelium (RPE) yields many morphologic and functional consequences, including death of the photoreceptor cells, Müller cell hypertrophy, and inner retinal rewiring. Many of these changes are due to the separation-induced activation of specific genes. In this work, we define the gene transcription profile within the retina as a function of time after detachment. We also define the early activation of kinases that might be responsible for the detachment-induced changes in gene transcription. Methods: Separation of the retina from the RPE was induced in Brown-Norway rats by the injection of 1% hyaluronic acid into the subretinal space. Retinas were harvested at 1, 7, and 28 days after separation. Gene transcription profiles for each time point were determined using the Affymetrix Rat 230A gene microarray chip. Transcription levels in detached retinas were compared to those of nondetached retinas with the BRB-ArrayTools Version 3.6.0 using a random variance analysis of variance (ANOVA) model. Confirmation of the significant transcriptional changes for a subset of the genes was performed using microfluidic quantitative real-time polymerase chain reaction (qRT-PCR) assays. Kinase activation was explored using Western blot analysis to look for early phosphorylation of any of the 3 main families of mitogen-activated protein kinases (MAPK): the p38 family, the Janus kinase family, and the p42/p44 family. Results: Retinas separated from the RPE showed extensive alterations in their gene transcription profile. Many of these changes were initiated as early as 1 day after separation, with significant increases by 7 days. ANOVA analysis defined 144 genes that had significantly altered transcription levels as a function of time after separation when setting a false discovery rate at ≤0.1. Confirmatory RT-PCR was performed on 51 of these 144 genes. Differential transcription detected on the microarray

  7. Analysis of Effect of SRT on Biological Phosphorus Removal%泥龄对生物除磷效率影响的分析

    李勇; 黄勇; 潘杨


    In this paper,the effect of solids-retention time(SRT)on effect of biological phosphorus removal from wastewater is analyzed based on a steady-state kinetic model. It is indicated that short SRT can increase phosphorus removal by anabolism pathway due to the increase of surplus sludge discharge. If the same amount of phosphorus removal is expected,the content of poly-phosphate in surplus sludge should be higher in long STR than that in short SRT. This,in turn,implies a better capacity of accumulating phosphate is required for sludge with long STR. Because there are no sufficient evidences supporting this conclusion,it is considered that the investigation on application of short STR is encouraged for biological enhanced phosphorus removal processes.%文章采用Lawrence-McCarty模式,分析了泥龄对生物除磷效率的影响。分析结果表明当泥龄由20天缩短为5天时,系统的剩余污泥排放量增加近一倍,同化脱磷效率可由15.7%增加至30.7%;短泥龄系统对TBOD/TP值的敏感性强于长泥龄系统;若期望从废水中去除的磷量不变,则要求剩余污泥含磷量,即污泥的聚磷能力随泥龄的增加而增加。笔者认为,深入研究短泥龄系统的运行,对提高生物除磷的效率具有重要意义。

  8. Effects of hydraulic retention time (HRT) and sludge retention time (SRT) on the treatment of nitrobenzene in AMBR/CSTR reactor systems.

    Kuscu, O S; Sponza, D T


    The effect of hydraulic retention time (HRT) and solid retention time (SRT) on the biodegradation of a synthetic wastewater containing nitrobenzene was investigated in a sequential anaerobic migrating blanket reactor (AMBR) and aerobic completely stirred tank reactor (CSTR) system. Reactor performance was evaluated at six different HRTs (1,1.5,2,2.5,3.5,5.19 and 10.38 days) and at six different SRTs (32,53,76,217,415 and 932 days). The influent COD and nitrobenzene concentration were kept constant at 3000 mg l(-1) and 60 mg l(-1), respectively, during continuous operation. The maximum COD removal efficiency was found to be 92% at a HRT of 10.38 days and a SRT of 932 days in AMBR reactor. However, nitrobenzene removal efficiencies were found to be 99.9% through all HRTs and SRTs in AMBR reactor. Most of the influent COD and nitrobenzene concentrations were removed in first compartment of AMBR. The total and methane gas production rates increased from 2760 ml day(-1) to 11760 ml day(-1) and from 1300 ml day(-1) to 3331 ml day(-1), respectively, as the HRT was decreased from 10.38 to 1 day in AMBR. However, methane percentage decreased from 47% to 28% with decreased HRTs and SRTs. The methanogens inhibition was observed at lower HRTs. pH values in the compartments and the effluent of AMBR was between optimum values. TVFA concentrations in effluent of AMBR were measured as zero until a HRT of 3.5 days. In the aerobic CSTR reactor, the COD removal efficiency decreased from 79% to 68% with decreased HRT from 6.79 to 0.67 days. It was found that the nitrobenzene transformed to aniline under anaerobic phase, and then the aniline mineralized in the oxidative stage, with efficiencies varying between 79% to 99.9%, in anaerobic/aerobic reactor system.

  9. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease.

    John Marshall

    Full Text Available Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal. This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3 in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT. Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638 was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.

  10. Lessons learned from gene therapy for color blindness in primates

    NEITZ, J


    Color blindness is the most common genetic disorder. The possibility of curing color blindness using gene therapy was explored by adding a third type of cone pigment to dichromatic retinas of squirrel monkeys...

  11. Retina neural circuitry seen with particle detector technology

    CERN Bulletin


    Using particle physics techniques, high energy physics researchers have recently provided new insight into neural circuits inside the retina. After uncovering a new type of retinal cell and mapping how the retina deals with colours, the team from Santa Cruz (US), Krakow and Glasgow is now turning its attention to more complex issues such as how the retina gets wired up and how the brain deals with the signals it receives from the retina. All this using technology derived from high-density, multistrip silicon detectors…   Seen from the point of view of a particle physicist, eyes are image detectors that can gather many different types of data: light and dark, different colours, motion, etc. In particular, the retina, a thin tissue that lines the back of the eye, is a biological pixel detector that detects light and converts it to electrical signals that travel through the optic nerve to the brain. Neurobiologists know that many different cell types are involved in these processes, but they...

  12. Selective Gene Transfer to the Retina Using Intravitreal Ultrasound Irradiation

    Shozo Sonoda


    Full Text Available This paper aims to evaluate the efficacy of intravitreal ultrasound (US irradiation for green fluorescent protein (GFP plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL and bubble liposomes (BLs; 50 μL was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM of GFP-positive cells (32±4.9; n=7; P<0.01 . No GFP-positive cells were observed in the control eyes (n=7. Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value.

  13. Neuropeptide Y system in the retina: From localization to function.

    Santos-Carvalho, Ana; Ambrósio, António Francisco; Cavadas, Cláudia


    The retina is a highly complex structure where several types of cells communicate through countless different molecules to codify visual information. Each type of cells plays unique roles in the retina, presenting a singular expression of neurotransmitters. Some neurotransmitter systems in the retina are well understood, while others need to be better explored to unravel the intricate signaling system involved. Neuropeptide Y (NPY), a 36 amino acid peptide, is one of the most common peptide neurotransmitter in the CNS and a highly conserved peptide among species. We review the localization of NPY and NPY receptors (mainly NPY Y1, Y2, Y4 and Y5) in retinal cells. Common features of the expression of NPY and NPY receptors in mammalian and non-mammalian species indicate universal roles of this system in the retina. In the present review, we highlight the putative roles of NPY receptor activation in the retina, discussing, in particular, their involvement in retinal development, neurotransmitter release modulation, neuroprotection, microglia and Muller cells function, retinal pigmented epithelium changes, retinal endothelial physiology and proliferation of retinal progenitor cells. Further studies are needed to confirm that targeting the NPY system might be a potential therapeutic strategy for retinal degenerative diseases.

  14. Bmp4 from the optic vesicle specifies murine retina formation.

    Huang, Jie; Liu, Ying; Oltean, Alina; Beebe, David C


    Previous studies of mouse embryos concluded that after the optic vesicle evaginates from the ventral forebrain and contacts the surface ectoderm, signals from the ectoderm specify the distal region of the optic vesicle to become retina and signals from the optic vesicle induce the lens. Germline deletion of Bmp4 resulted in failure of lens formation. We performed conditional deletion of Bmp4 from the optic vesicle to test the function of Bmp4 in murine eye development. The optic vesicle evaginated normally and contacted the surface ectoderm. Lens induction did not occur. The optic cup failed to form and the expression of retina-specific genes decreased markedly in the distal optic vesicle. Instead, cells in the prospective retina expressed genes characteristic of the retinal pigmented epithelium. We conclude that Bmp4 is required for retina specification in mice. In the absence of Bmp4, formation of the retinal pigmented epithelium is the default differentiation pathway of the optic vesicle. Differences in the signaling pathways required for specification of the retina and retinal pigmented epithelium in chicken and mouse embryos suggest major changes in signaling during the evolution of the vertebrate eye.

  15. Characterization of Predictive Behavior of a Retina by Mutual Information

    Kevin Sean Chen


    Full Text Available Probing a bullfrog retina with spatially uniform light pulses of correlated stochastic intervals, we calculate the mutual information between the spiking output at the ganglion cells measured with multi-electrode array (MEA and the interval of the stimulus at a time shift later. The time-integrated information from the output about the future stimulus is maximized when the mean interval of the stimulus is within the dynamic range of the well-established anticipative phenomena of omitted-stimulus responses for the retina. The peak position of the mutual information as a function of the time shift is typically negative considering the processing delay of the retina. However, the peak position can become positive for long enough correlation time of the stimulus when the pulse intervals are generated by a Hidden Markovian model (HMM. This is indicative of a predictive behavior of the retina which is possible only when the hidden variable of the HMM can be recovered from the history of the stimulus for a prediction of its future. We verify that stochastic intervals of the same mean, variance, and correlation time do not result in the same predictive behavior of the retina when they are generated by an Ornstein–Uhlenbeck (OU process, which is strictly Markovian.

  16. Advances in gene therapy technologies to treat retinitis pigmentosa


    Hilda Petrs-Silva, Rafael LindenInstitute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilAbstract: Retinitis pigmentosa (RP) is a class of diseases that leads to progressive degeneration of the retina. Experimental approaches to gene therapy for the treatment of inherited retinal dystrophies have advanced in recent years, inclusive of the safe delivery of genes to the human retina. This review is focused on the development of gene therapy for RP using recombinant a...

  17. The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma

    Wobb, Jessica; Krueger, Sarah A.; Kane, Jonathan L.; Galoforo, Sandra; Grills, Inga S.; Wilson, George D.; Marples, Brian, E-mail:


    Purpose: To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT). Methods and Materials: Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0.2 Gy × 10 with 3-min pulse interval) to total doses of 20 Gy (UT14) or 40 Gy (UT15) using a clinical 5-day on/2-day off schedule. Treatment response was assessed by changes in tumor volume, {sup 18}F-fluorodeoxyglucose (FDG) (tumor metabolism), and {sup 18}F-fluoromisonidazole (FMISO) (hypoxia) positron emission tomography (PET) imaging before, at midpoint, and after treatment. Tumor hypoxia using pimonidazole staining and vascular density (CD34 staining) were assessed by quantitative histopathology. Results: UT15 and UT14 tumors responded similarly in terms of growth delay to either SRT or PRT. When compared with UT14 tumors, UT15 tumors demonstrated significantly lower uptake of FDG at all time points after irradiation. UT14 tumors demonstrated higher levels of tumor hypoxia after SRT when compared with PRT as measured by {sup 18}F-FMISO PET. By contrast, no differences were seen in {sup 18}F-FMISO PET imaging between SRT and PRT for UT15 tumors. Histologic analysis of pimonidazole staining mimicked the {sup 18}F-FMISO PET imaging data, showing an increase in hypoxia in SRT-treated UT14 tumors but not PRT-treated tumors. Conclusions: Differences in {sup 18}F-FMISO uptake for UT14 tumors after radiation therapy between PRT and SRT were measurable despite the similar tumor growth delay responses. In UT15 tumors, both SRT and PRT were equally effective at reducing tumor hypoxia to a significant level as measured by {sup 18}F-FMISO and pimonidazole.

  18. Novel Methodology for Creating Macaque Retinas with Sortable Photoreceptors and Ganglion Cells

    Shreyasi Choudhury


    Full Text Available Purpose: The ability to generate macaque retinas with sortable cell populations would be of great benefit to both basic and translational studies of the primate retina. The purpose of our study was therefore to develop methods to achieve this goal by selectively labeling, in life, photoreceptors (PRs and retinal ganglion cells (RGCs with separate fluorescent markers. Methods: Labeling of macaque (Macaca fascicularis PRs and RGCs was accomplished by subretinal delivery of AAV5-hGRK1-GFP, and retrograde transport of micro-ruby™ from the lateral geniculate nucleus, respectively. Retinas were anatomically separated into different regions. Dissociation conditions were optimized, and cells from each region underwent fluorescent activated cell sorting (FACS. Expression of retinal cell type- specific genes was assessed by quantitative real-time PCR to characterize isolated cell populations. Results: We show that macaque PRs and RGCs can be simultaneously labeled in-life and enriched populations isolated by FACS. Recovery from different retinal regions indicated efficient isolation/enrichment for PRs and RGCs, with the macula being particularly amendable to this technique. Conclusions: The methods and materials presented here allow for the identification of novel reagents designed to target retinal ganglion cells and/or photoreceptors in a species that is phylogenetically and anatomically similar to human. These techniques will enable screening of intravitreally- delivered AAV capsid libraries for variants with increased tropism for PRs and/or RGCs and the evaluation of vector tropism and/or cellular promoter activity of gene therapy vectors in a clinically relevant species.

  19. Tumor vasoproliferativo de retina.: Reporte de dos casos Vasoproliferative retinal tumor.: Report of two cases

    Danaides Arencibia González


    Full Text Available El tumor vasoproliferativo de retina es una condición rara y benigna que presenta una lesión exudativa de retina periférica. La lesión puede ser clasificada en primaria (idiopática o secundaria a otros procesos oculares. Las opciones terapéuticas incluyen observación, crioablación tisular, fotocoagulación láser, remoción quirúrgica mediante vitrectomía, terapia fotodinámica y braquiterapia epiescleral con isótopos radioactivos, asociadas o no al uso de antiangiogénicos o antiinflamatorios, siendo la elección de la modalidad de manejo particular en cada caso. Presentamos dos casos en pacientes femeninas portadoras de esta condición de los que describimos las características más importantes del cuadro clínico, retinografías, angiografía fluoresceínica y ecografía, así como el manejo y curso evolutivo-terapéutico.Vasoproliferative retinal tumor is a rare and benign condition that presents as an exudative lesion in the peripheral retina. The lesion can be classified in primary (idiopathic or secondary to other ocular processes. Therapeutic options include observation, cryotherapy, laser photocoagulation, surgical removal by pars plana vitrectomy, photodynamic therapy and epiescleral brachytheraphy with radio-active isotopes associated or not to the use of anti-angiogenic or anti-inflammatory drugs. The selection of a particular management modality depends on the type of case. Two female patients affected with this condition were presented; the most important characteristics in their clinical pictures, as well as the results of other tests as retinography, fluorescent and ICG angiography and echography were described. The management and the therapeutical and evolutive course of both patients were also discussed.

  20. Primitive neuroectodermal tumor/Ewing sarcoma of the retina.

    Grossniklaus, Hans E; Shehata, Bahig; Sorensen, Poul; Bergstrom, Chris; Hubbard, G Baker


    An 11-year-old boy underwent enucleation of his left eye for an intraocular tumor. Examination showed a small, round blue cell tumor arising in the peripheral retina near the ciliary body. Immunohistochemical stain results were positive for neuron-specific enolase, synaptophysin, cluster of differentiation 99 (CD99), Friend leukemia integration 1, and CD56. Ultrastructural findings included occasional intracytoplasmic dense core granules. Polymerase chain reaction of the tumor showed a Ewing sarcoma/Friend leukemia integration gene fusion product. The tumor was classified as a primitive neuroectodermal tumor/Ewing sarcoma of the retina and should be distinguished from retinoblastoma. To our knowledge, this is the first case of primary primitive neuroectodermal tumor of the retina.

  1. The mechanism of pattern formation in the developing drosophila retina

    SUN QiCheng


    The biological patterning of the drosophila retina in vivo has striking resemblance to liquid bubbles, in which the surface mechanics due to N-cadherin within a sub-group of retina cells can be mimicked by surface tension. In this work, the aggregating patterns were reasonably simplified into 2D clusters consisting of 2-6 identical bubbles confined within a shrinking boundary. By using a hybrid fluid dynamics model proposed for liquid foams, the aggregating process of 2-6 retina cells was studied. Assuming the minimal perimeter for patterning cells to be the condition of stability patterns, the stable converged patterns we simulated in this work are the same as the experimental observations. More importantly, a new pattern of 6 cells was obtained which was found physically more stable than the other two reported by Hayashi and Carthew[1]. Aggregating perimeters of cells, i.e. the surface energy, showed a good linear fit with the cell numbers.

  2. The mechanism of pattern formation in the developing drosophila retina


    The biological patterning of the drosophila retina in vivo has striking resemblance to liquid bubbles, in which the surface mechanics due to N-cadherin within a sub-group of retina cells can be mimicked by surface tension. In this work, the aggregating patterns were reasonably simplified into 2D clusters consisting of 2—6 identical bubbles confined within a shrinking boundary. By using a hybrid fluid dy-namics model proposed for liquid foams, the aggregating process of 2―6 retina cells was studied. Assuming the minimal perimeter for patterning cells to be the condition of stability patterns, the stable converged patterns we simulated in this work are the same as the experimental observations. More importantly, a new pattern of 6 cells was obtained which was found physically more stable than the other two reported by Hayashi and Carthew[1]. Aggregating perimeters of cells, i.e. the surface energy, showed a good linear fit with the cell numbers.

  3. The architecture of functional interaction networks in the retina.

    Ganmor, Elad; Segev, Ronen; Schneidman, Elad


    Sensory information is represented in the brain by the joint activity of large groups of neurons. Recent studies have shown that, although the number of possible activity patterns and underlying interactions is exponentially large, pairwise-based models give a surprisingly accurate description of neural population activity patterns. We explored the architecture of maximum entropy models of the functional interaction networks underlying the response of large populations of retinal ganglion cells, in adult tiger salamander retina, responding to natural and artificial stimuli. We found that we can further simplify these pairwise models by neglecting weak interaction terms or by relying on a small set of interaction strengths. Comparing network interactions under different visual stimuli, we show the existence of local network motifs in the interaction map of the retina. Our results demonstrate that the underlying interaction map of the retina is sparse and dominated by local overlapping interaction modules.

  4. Control of rod shedding in the frog retina.

    Basinger, S F; Hollyfield, J G


    In all vertebrate species examined thus far, rod outer segment shedding follows a cyclic pattern in which the outer segment tips are shed shortly after the onset of light. Work in the rat retina suggests that rod shedding may follow a circadian rhythm which is controlled by one or more circadian oscillators. Our results in the frog retina are significantly different in that: rod shedding can be driven by the onset of light or other environmental cues; shedding does not persist in constant darkness; shedding is unaffected in frogs with chronic unilateral or bilateral optic nerve section; and shedding will rapidly phase shift to the time of light onset on a wide variety of diurnal cycles. Thus, rod shedding in the frog retina does not appear to be a classical circadian rhythm.

  5. A Possible Role of Neuroglobin in the Retina After Optic Nerve Injury: A Comparative Study of Zebrafish and Mouse Retina.

    Sugitani, Kayo; Koriyama, Yoshiki; Ogai, Kazuhiro; Wakasugi, Keisuke; Kato, Satoru


    Neuroglobin (Ngb) is a new member of the family of heme proteins and is specifically expressed in neurons of the central and peripheral nervous systems in all vertebrates. In particular, the retina has a 100-fold higher concentration of Ngb than do other nervous tissues. The role of Ngb in the retina is yet to be clarified. Therefore, to understand the functional role of Ngb in the retina after optic nerve injury (ONI), we used two types of retina, from zebrafish and mice, which have permissible and non-permissible capacity for nerve regeneration after ONI, respectively. After ONI, the Ngb protein in zebrafish was upregulated in the amacrine cells within 3 days, whereas in the mouse retina, Ngb was downregulated in the retinal ganglion cells (RGCs) within 3 days. Zebrafish Ngb (z-Ngb) significantly enhanced neurite outgrowth in retinal explant culture. According to these results, we designed an overexpression experiment with the mouse Ngb (m-Ngb) gene in RGC-5 cells (retinal precursor cells). The excess of m-Ngb actually rescued RGC-5 cells under hypoxic conditions and significantly enhanced neurite outgrowth in cell culture. These data suggest that mammalian Ngb has positive neuroprotective and neuritogenic effects that induce nerve regeneration after ONI.

  6. Artificial retina: the multichannel processing of the mammalian retina achieved with a neuromorphic asynchronous light acquisition device.

    Lorach, Henri; Benosman, Ryad; Marre, Olivier; Ieng, Sio-Hoi; Sahel, José A; Picaud, Serge


    Objective. Accurate modeling of retinal information processing remains a major challenge in retinal physiology with applications in visual rehabilitation and prosthetics. Most of the current artificial retinas are fed with static frame-based information, losing thereby the fundamental asynchronous features of biological vision. The objective of this work is to reproduce the spatial and temporal properties of the majority of ganglion cell (GC) types in the mammalian retina. Approach. Here, we combined an asynchronous event-based light sensor with a model pulling nonlinear subunits to reproduce the parallel filtering and temporal coding occurring in the retina. We fitted our model to physiological data and were able to reconstruct the spatio-temporal responses of the majority of GC types previously described in the mammalian retina (Roska et al 2006 J. Neurophysiol. 95 3810-22). Main results. Fitting of the temporal and spatial components of the response was achieved with high coefficients of determination (median R(2) = 0.972 and R(2) = 0.903, respectively). Our model provides an accurate temporal precision with a reliability of only few milliseconds-peak of the distribution at 5 ms-similar to biological retinas (Berry et al 1997 Proc. Natl Acad. Sci. USA 94 5411-16; Gollisch and Meister 2008 Science 319 1108-11). The spiking statistics of the model also followed physiological measurements (Fano factor: 0.331). Significance. This new asynchronous retinal model therefore opens new perspectives in the development of artificial visual systems and visual prosthetic devices.

  7. Effects of endothelin-1 eyedrops on the retina in rats.

    Masuzawa, Koichi; Miyauchi, Takashi; Takanashi, Masakatsu; Ogata, Takehiro; Yamaguchi, Iwao; Goto, Katsutoshi


    Eye disorder accompanied with chronic retinal microvascular obstruction, such as diabetic retinopathy, exists in many diseases. However, it is difficult to produce this model experimentally in the animal eye. Endothelin-1 eyedrops were prepared in order to examine whether the eyedrops affect the rat retina and whether we can produce an obstruction model. Endothelin-1 eyedrops diluted by artificial tears in seven stages from 4 x 10(-5) M to 4 x 10(-11) M were arranged. We administered this solution three times a day in the left eye of male Sprague-Dawley rats. Artificial tears alone were applied to the right eye as a control vehicle. After 2 weeks, rats were sacrificed under anesthesia and the retinal tissues were isolated. As an index to the action of endothelin- 1 eyedrops to the retina, the expressions of endothelin-A (ETA) and endothelin-B (ETB) receptors in the retina were compared in both eyes. Frozen sections of the retina were immunostained to reveal the distribution of the ETA and ETB receptors. We also examined ETA and ETB mRNA expression by quantitative real-time polymerase chain reaction. As a result, the expressions of ETA and ETB receptors are reduced with both immunostaining and the mRNA levels in the left eye, in which endothelin-1 eyedrops were applied at 4 x 10(-5) M. It is suggested that endothelin-1 eyedrops affected the retina and the possibility of producing the experimental model of chronic microvascular obstruction in the rat retina.

  8. Postprostatectomy radiation therapy: an evidence-based review.

    Mishra, Mark V; Champ, Colin E; Den, Robert B; Scher, Eli D; Shen, Xinglei; Trabulsi, Edouard J; Lallas, Costas D; Knudsen, Karen E; Dicker, Adam P; Showalter, Timothy N


    While the majority of men with localized prostate cancer who undergo a radical prostatectomy will remain disease free, men with certain clinical and pathological features are known to be at an increased risk for developing a biochemical recurrence and, ultimately, distant metastatic disease. The optimal management of these patients continues to be a source of controversy. To date, three randomized Phase III trials have demonstrated that adjuvant radiation therapy (ART) for patients with certain adverse pathological features results in an improvement in several clinically-relevant end points, including biochemical recurrence-free survival and overall survival. Despite the evidence from these trials showing a benefit for ART, many believe that ART results in overtreatment and unwarranted treatment morbidity for a significant number of patients. Many physicians, therefore, instead advocate for close observation followed by early salvage radiation therapy (SRT) at the time of a biochemical recurrence. The purpose of this review is to evaluate the evidence for and to distinguish between ART and early SRT. We will also highlight current and future areas of research for this patient population, including radiation treatment dose escalation, hypofractionation and androgen deprivation therapy. We will also discuss the cost-effectiveness of ART and early SRT.

  9. Neurokinin 1 Receptor Expression in the Rat Retina

    Casini, Giovanni; Rickman, Dennis W.; Sternini, Catia; Brecha, Nicholas C.


    Tachykinin (TK) peptides influence neuronal activity in the inner retina of mammals. The aim of this investigation was to determine the cellular localization of the neurokinin 1 receptor (NK1), whose preferred ligand is the TK peptide substance P (SP), in the rat retina. These studies used a polyclonal antiserum directed to the C-terminus of rat NK1. The majority of NK1-immunoreactive (IR) cells were located in the proximal inner nuclear layer (INL), and very rarely they were found in the dis...

  10. Retina-like sensor image coordinates transformation and display

    Cao, Fengmei; Cao, Nan; Bai, Tingzhu; Song, Shengyu


    For a new kind of retina-like senor camera, the image acquisition, coordinates transformation and interpolation need to be realized. Both of the coordinates transformation and interpolation are computed in polar coordinate due to the sensor's particular pixels distribution. The image interpolation is based on sub-pixel interpolation and its relative weights are got in polar coordinates. The hardware platform is composed of retina-like senor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes the real-time image acquisition, coordinate transformation and interpolation.

  11. [Damage and functional recovery of the mouse retina after exposure to ionizing radiation and methylnitrosourea].

    Vinogradova, Iu V; Tronov, V A; Liakhova, K N; Poplinskaia, V A; Ostrovskiĭ, M A


    The eye retina consists of terminally differentiated cells that have lost their ability to proliferate. The death of these cells leads tothe loss of sight. The mice retina is characterized by relatively high resistance to radiation, which is provided by its ability to repair damage caused by environmental factors. The aim of our work was to assess the damaging effect of ionizing radiation and methylnitrosourea (MNU) on the DNA structure in the mouse retina, the functional activity of the retina, and its ability to recover in vivo. The results confirm the ability of the mature retina to structural and functional recovery. Adapting influence of low dose chemical agent increases retina resistance to cytotoxic dose of genotoxicants and prevents degeneration of photoreceptor layer of the retina. The results show the possibility of neurohormesis effect in the mice retina after exposure to ionizing radiation and chemicals.

  12. Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter.

    Jake Bedore

    Full Text Available Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina.A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5 deletion of VAChT (VAChTSix3-Cre-flox/flox and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina.

  13. File list: InP.Oth.05.AllAg.Retina [Chip-atlas[Archive

    Full Text Available InP.Oth.05.AllAg.Retina mm9 Input control Others Retina SRX1365331,SRX018605,SRX018...601,SRX018603,SRX1365332,SRX1365338,SRX1365337,SRX1365333,SRX1365336,SRX1365334,SRX1365335 ...

  14. File list: InP.Oth.50.AllAg.Retina [Chip-atlas[Archive

    Full Text Available InP.Oth.50.AllAg.Retina mm9 Input control Others Retina SRX018603,SRX018605,SRX0186...01,SRX1365338,SRX1365337,SRX1365334,SRX1365336,SRX1365335,SRX1365331,SRX1365333,SRX1365332 ...

  15. File list: Oth.Oth.10.AllAg.Retina [Chip-atlas[Archive

    Full Text Available Oth.Oth.10.AllAg.Retina mm9 TFs and others Others Retina SRX151679,SRX429085,SRX018...X429082,SRX700316,SRX018604,SRX1365304,SRX700325 ...


    To understand mechanisms of neurotoxicity in susceptible populations, we examined age-related changes in constitutive gene expression in the retinas of young (4mos), middle-aged (11 mos) and aged (23 mos) male Long Evans rats. Derived from a pouch of the forebrain during develop...

  17. The Virtual Retina: Is Good Educational Technology Always Strategic?

    Dowie, Sandra

    Educational technology units must continually monitor their strategic plans to ensure that they are aligned with the realities of their institutions. Strategic dissonance occurs when previously successful strategies are no longer achieving the same positive outcomes. The Virtual Retina CD-ROM project is used in this paper as an example of…

  18. Functional architecture of the retina: development and disease.

    Hoon, Mrinalini; Okawa, Haruhisa; Della Santina, Luca; Wong, Rachel O L


    Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina.

  19. A silicon retina that reproduces signals in the optic nerve.

    Zaghloul, Kareem A; Boahen, Kwabena


    Prosthetic devices may someday be used to treat lesions of the central nervous system. Similar to neural circuits, these prosthetic devices should adapt their properties over time, independent of external control. Here we describe an artificial retina, constructed in silicon using single-transistor synaptic primitives, with two forms of locally controlled adaptation: luminance adaptation and contrast gain control. Both forms of adaptation rely on local modulation of synaptic strength, thus meeting the criteria of internal control. Our device is the first to reproduce the responses of the four major ganglion cell types that drive visual cortex, producing 3600 spiking outputs in total. We demonstrate how the responses of our device's ganglion cells compare to those measured from the mammalian retina. Replicating the retina's synaptic organization in our chip made it possible to perform these computations using a hundred times less energy than a microprocessor-and to match the mammalian retina in size and weight. With this level of efficiency and autonomy, it is now possible to develop fully implantable intraocular prostheses.

  20. A public confession: the retina trumpets its failed predictions.

    Holy, Timothy E


    To compensate for delays of phototransduction, the retina anticipates the future by extrapolating the position of a moving object. But what if the object's motion changes, and the extrapolation is wrong? In this issue of Neuron, Schwartz and colleagues show that these prediction failures trigger a large burst of firing that helps to rapidly correct the neural representation of the object's new position.

  1. Interleukin-1beta mediates ischemic injury in the rat retina.

    Yoneda, S; Tanihara, H; Kido, N; Honda, Y; Goto, W; Hara, H; Miyawaki, N


    Two types of experiment were performed to examine the role of interleukin-1beta in ischemia-induced damage in the rat retina. In the in vivo study, enzyme-linked immunosorbent assay was used to investigate the expression of immunoreactive interleukin-1beta in the rat retina following a hypertension-induced ischemia/reperfusion, while the effect of a recombinant human interleukin-1 receptor antagonist or an anti-interleukin-1beta neutralizing antibody on the ischemia-induced damage was examined histologically. A transient increase in the expression of immunoreactive interleukin-1beta was observed in the retina 3-12 hr after reperfusion, and morphometric evaluation at 7 days after the ischemia showed a decrease in cell numbers in the ganglion cell layer and a decreased thickness of the inner plexiform layer with no change in the other retinal layers. Intravitreal injection of interleukin-1 receptor antagonist (1 or 10 ng per eye) or anti-interleukin-1beta antibody (50 or 500 ng per eye) 5 min before the onset of the ischemia reduced the damage. In the in vitro study, interleukin-1 receptor antagonist (500 ng ml(-1)) significantly reduced glutamate-induced neurotoxicity in rat cultured retinal neurons. These results suggest that interleukin-1 plays an important role in mediating ischemic and excitotoxic damage in the retina, and that interleukin-1 inhibitors may be therapeutically useful against neuronal injury caused by optic nerve or retinal diseases such as glaucoma and central retinal artery or vein occlusion.

  2. Gene expression profiles of the developing human retina

    WANG Feng; LI Huiming; LIU Wenwen; XU Ping; HU Gengxi; CHENG Yidong; JIA Libin; HUANG Qian


    Retina is a multilayer and highly specialized tissue important in converting light into neural signals. In humans, the critical period for the formation of complex multiplayer structure takes place during embryogenesis between 12 and 28 weeks. The morphologic changes during retinal development in humans have been studied but little is known about the molecular events essential for the formation of the retina. To gain further insights into this process, cDNA microarrays containing 16361 human gene probes were used to measure the gene expression levels in retinas. Of the 16361 genes, 68.7%, 71.4% and 69.7% showed positive hybridization with cDNAs made from 12-16 week fetal, 22-26 week fetal and adult retinas. A total of 814 genes showed a minimum of 3-fold changes between the lowest and highest expression levels among three time points and among them, 106 genes had expression levels with the hybridization intensity above 100 at one or more time points. The clustering analysis suggested that the majority of differentially expressed genes were down-regulated during the retinal development. The differentially expressed genes were further classified according to functions of known genes, and were ranked in decreasing order according to frequency: development, differentiation, signal transduction, protein synthesis and translation, metabolism, DNA binding and transcription, DNA synthesis-repair-recombination, immuno-response, ion channel- transport, cell receptor, cytoskeleton, cell cycle, pro-oncogene, stress and apoptosis related genes. Among these 106 differentially expressed genes, 60 are already present in NEI retina cDNA or EST Databank but the remaining 46 genes are absent and thus identified as "function unknown". To validate gene expression data from the microarray, real-time RT-PCR was performed for 46 "function unknown" genes and 6 known retina specific expression genes, and β-actin was used as internal control. Twenty-seven of these genes showed very similar

  3. A simple method for in vivo labelling of infiltrating leukocytes in the mouse retina using indocyanine green dye

    Dawn A. Sim


    Full Text Available We have developed a method to label and image myeloid cells infiltrating the mouse retina and choroid in vivo, using a single depot injection of indocyanine green dye (ICG. This was demonstrated using the following ocular models of inflammation and angiogenesis: endotoxin-induced uveitis, experimental autoimmune uveoretinitis and laser-induced choroidal neovascularization model. A near-infrared scanning ophthalmoscope was used for in vivo imaging of the eye, and flow cytometry was used on blood and spleen to assess the number and phenotype of labelled cells. ICG was administered 72 h before the induction of inflammation to ensure clearance from the systemic circulation. We found that in vivo intravenous administration failed to label any leukocytes, whereas depot injection, either intraperitoneal or subcutaneous, was successful in labelling leukocytes infiltrating into the retina. Progression of inflammation in the retina could be traced over a period of 14 days following a single depot injection of ICG. Additionally, bright-field microscopy, spectrophotometry and flow cytometric analysis suggest that the predominant population of cells stained by ICG are circulating myeloid cells. The translation of this approach into clinical practice would enable visualization of immune cells in situ. This will not only provide a greater understanding of pathogenesis, monitoring and assessment of therapy in many human ocular diseases but might also open the ability to image immunity live for neurodegenerative disorders, cardiovascular disease and systemic immune-mediated disorders.

  4. Molecular cloning and expression in Escherichia coli of an exo-levanase gene from the endophytic bacterium Gluconacetobacter diazotrophicus SRT4.

    Menéndez, Carmen; Hernández, Lázaro; Selman, Guillermo; Mendoza, Milady F; Hevia, Pedro; Sotolongo, Mailin; Arrieta, Juan G


    Gluconacetobacter diazotrophicus produces levan from sucrose by a secreted levansucrase (LsdA). A levanase-encoding gene ( lsdB), starting 51 bp downstream of the lsdA gene, was cloned from strain SRT4. The lsdB gene (1605 bp) encodes a protein (calculated molecular mass 58.4 kDa) containing a putative 36-amino-acid signal peptide at the N-terminus. The deduced amino acid sequence shares 34%, 33%, 32%, and 29% identities with levanases from Actinomyces naeslundii, Bacillus subtilis, Paenibacillus polymyxa, and Bacteroides fragilis, respectively. The lsdB expression in Escherichia coli under the control of the T7 RNA polymerase promoter resulted in an active enzyme which hydrolyzed levan, inulin, 1-kestose, raffinose, and sucrose, but not melezitose. Levanase activity was maximal at pH 6.0 and 30 degrees C, and it was not inhibited by the metal ion chelator EDTA or the denaturing agents dithiothreitol and beta-mercaptoethanol. The recombinant LsdB showed a fourfold higher rate of hydrolysis on levan compared to inulin, and the reaction on both substrates resulted in the successive liberation of the terminal fructosyl residues without formation of intermediate oligofructans, indicating a non-specific exo-levanase activity.

  5. [The ultrastructure changes of rabbit retina after periodical vacuum suction].

    Li, Shan-shan; Zhou, Xiao-dong; Chu, Ren-yuan


    To study the effects of periodical vacuum-suction of different pressures on the ultrastructure of rabbits' retina. Rabbits involved in the present study were divided into a control group and four treatment groups, which were treated with vacuum-suction of different pressures through scleral suction ring. The suction pressure was increased at a rate of 100 mm Hg/3 sec (1 mm Hg = 0.133 kPa) and reached (200 +/- 20) mm Hg (group I), (300 +/- 20) mm Hg (group II); (400 +/- 20) mm Hg (group III) and (500 +/- 20) mm Hg (group IV). The suction pressure was maintained for 5 seconds before released to zero. The corresponding intraocular pressure examined by Tonopen was 35 mm Hg, 45 mm Hg, 55 mm Hg and 75 mm Hg in these 4 groups, respectively. This circle was repeated for 10 times with 1 minute interval. The test was repeated every other day. The retina was examined by electron microscope after 2 weeks. There was no obvious difference in the retina ultrastructure between the control group and group I. The retina ultrastructure changed slightly in group II which showed more active metabolism. Some significant changes were found in group III and group IV with cell necrosis in group IV. Different elevations of intraocular pressure following periodical vacuum-suction have different effects on the retina of rabbit. Pressure less than 45 mm Hg has almost no effect, but some effects appear at 55 mm Hg pressure, and obviously damages are caused by 75 mm Hg pressure.

  6. Impact of bronchopulmonary dysplasia on brain and retina

    Annie Wing Hoi Poon


    Full Text Available Many premature newborns develop bronchopulmonary dysplasia (BPD, a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, ‘BPD’ group or room air (21% O2, ‘control’ group from postnatal day 4–14 (P4–14; the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001. This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=−0.49, P=0.02 and retina (r=−0.70, P=0.0008 structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

  7. Impact of bronchopulmonary dysplasia on brain and retina.

    Poon, Annie Wing Hoi; Ma, Emilie Xiao Hang; Vadivel, Arul; Jung, Suna; Khoja, Zehra; Stephens, Laurel; Thébaud, Bernard; Wintermark, Pia


    Many premature newborns develop bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, 'BPD' group) or room air (21% O2, 'control' group) from postnatal day 4-14 (P4-14); the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P<0.0001). This increase was associated with a decrease in some brain structures [especially the whole-brain surface (P=0.02)], as well as a decrease in the thickness of the retinal layers [especially the total retina (P=0.0008)], compared to the room air control group. In addition, a significant negative relationship was observed between the lung structures and the brain (r=-0.49,P=0.02) and retina (r=-0.70,P=0.0008) structures. In conclusion, hyperoxia exposure impaired lung, brain, and retina structures. More severe lung injuries correlated with more severe brain and retinal injuries. This result suggests that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

  8. Neural Degeneration in the Retina of the Streptozotocin-Induced Type 1 Diabetes Model

    Yoko Ozawa


    Full Text Available Diabetic retinopathy, a vision-threatening disease, has been regarded as a vascular disorder. However, impaired oscillatory potentials (OPs in the electroretinogram (ERG and visual dysfunction are recorded before severe vascular lesions appear. Here, we review the molecular mechanisms underlying the retinal neural degeneration observed in the streptozotocin-(STZ- induced type 1 diabetes model. The renin-angiotensin system (RAS and reactive oxygen species (ROS both cause OP impairment and reduced levels of synaptophysin, a synaptic vesicle protein for neurotransmitter release, most likely through excessive protein degradation by the ubiquitin-proteasome system. ROS also decrease brain-derived neurotrophic factor (BDNF and inner retinal neuronal cells. The influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively, are potential candidates for neuroprotective and preventive therapies to improve the visual prognosis.

  9. Hypofractionated Versus Standard Radiation Therapy With or Without Temozolomide for Older Glioblastoma Patients

    Arvold, Nils D. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Tanguturi, Shyam K. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Aizer, Ayal A. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Wen, Patrick Y.; Reardon, David A.; Lee, Eudocia Q.; Nayak, Lakshmi [Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Christianson, Laura W.; Horvath, Margaret C. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Dunn, Ian F.; Golby, Alexandra J.; Johnson, Mark D. [Department of Neurosurgery, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Claus, Elizabeth B. [Department of Neurosurgery, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); School of Public Health, Yale University, New Haven, Connecticut (United States); Chiocca, E. Antonio [Department of Neurosurgery, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Ligon, Keith L. [Department of Pathology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States); Alexander, Brian M., E-mail: [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, Massachusetts (United States)


    Purpose: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). Methods and Materials: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. Results: Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). Conclusions: With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall

  10. Pharmacological protection of the retina against damaging laser exposures: a feasibility study. Final report, January-December 1987

    Cartledge, R.M.; Glickman, R.D.; Elliott, W.R.


    Light damage to ocular tissues may occur through at least three mechanisms -- thermal, photochemical, or mechanical (photoacoustic) stress. These stress mechanisms may act singly, or in combination, depending on the intensity, wavelength, and temporal parameters of the damaging light exposure. Because some of these mechanisms involve biochemical intermediates, the possibility exists that appropriate pharmacological therapy might limit the extent of retinal light damage. This investigation determined the degree to which pharmacological pretreatments could protect a model retina against laser light damage. Five agents were examined for protective activity: an anti-inflammatory steroid hormone (dexamethasone); three antioxidants (3-aminotyrosine, vitamins C AND E); and a chelating agent (EGTA).

  11. [Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes].

    Echevarría, L; Villena, O; Nievas, T; Bellido, R


    A 58 year-old female was diagnosed with a juxtapapillary combined hamartoma of the retina and retinal pigment epithelium (CHR-RPE) in her left eye 14 years ago. Her visual acuity in that eye was 20/20. Recently, she came to our department with a sudden visual loss and metamorphopsis in her left eye. After performing funduscopy, angiography and OCT, she was diagnosed with choroidal neovascular membrane (CNVM) at lesion border, and started on antiangiogenic therapy. CHR-RPE, despite being a benign condition, may become complicated with severe visual impairment. Antiangiogenic therapy provides a good alternative to photodynamic therapy or laser photocoagulation for treatment of CNVM, avoiding adding iatrogenesis from these treatment to the complications associated with this pathology. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  12. In vitro and in vivo differentiation of human embryonic stem cells into retina-like organs and comparison with that from mouse pluripotent epiblast stem cells.

    Aoki, Hitomi; Hara, Akira; Niwa, Masayuki; Yamada, Yasuhiro; Kunisada, Takahiro


    Correctly inducing the differentiation of pluripotent hESCs to a specific lineage with high purity is highly desirable for regenerative cell therapy. Our first effort to perform in vitro differentiation of hESCs resulted in a limited recapitulation of the ocular tissue structures. When undifferentiated hESCs were placed in vivo into the ocular tissue, in this case into the vitreous cavity, 3-dimensional retina-like structures reminiscent of the invagination of the optic vesicle were generated. Immunohistochemical analysis confirmed the presence of both a neural retina-like cell layer and a retinal pigmented epithelium-like cell layer, possibly equivalent to the developing E12.5 mouse retina. Furthermore, mouse epiblast-derived stem cells, which are reported to share some characteristics with hESCs, but not with mouse ESCs, also generated retinal anlage-like structures in vivo. hESC-derived retina-like structures present a novel therapeutic possibility for retinal diseases and also provide a novel experimental system to study early human eye development.

  13. An analog VLSI chip emulating polarization vision of Octopus retina.

    Momeni, Massoud; Titus, Albert H


    Biological systems provide a wealth of information which form the basis for human-made artificial systems. In this work, the visual system of Octopus is investigated and its polarization sensitivity mimicked. While in actual Octopus retina, polarization vision is mainly based on the orthogonal arrangement of its photoreceptors, our implementation uses a birefringent micropolarizer made of YVO4 and mounted on a CMOS chip with neuromorphic circuitry to process linearly polarized light. Arranged in an 8 x 5 array with two photodiodes per pixel, each consuming typically 10 microW, this circuitry mimics both the functionality of individual Octopus retina cells by computing the state of polarization and the interconnection of these cells through a bias-controllable resistive network.

  14. Experimental Study of Effect of Perfluorohexyloctane to Retina

    Chunfang Li; Xiaoyan Ding; Lin Lu; Guanguang Feng; Huling Zheng


    Objective: To investigate the effect of perfluorohexvloctane to the retina of rabbit eyes.Methods: Perfluoroh-exyloctane (experimental group) or BSS(control group) intovitreous cavities of fifteen vitrectomized New Zealand white rabbits. A slit-lampbiomicroscope and an indirect ophthalmoscope were used to examine all the eyes pre- andpostoperation. Histopathological examination was performed after the rabbits weresacrificed. Results:Perfluorohexyloctane was injected into the vitreous cavity forming a single largeclear globe. No retinal detachment and cataract were found. The edema of outer plexiformlayer was significant, and then get thin, inner nuclear layer and ganglion cell bodies hada darker cytop: lasm and nucleoplasm. Conclusions: Perfluorohexyloctane in vitreous cavity had significant side effects on retinaAs a silicone solvent, it should be removed out completely after injection. We don′trecommend to use it as a new intraocular temponade.

  15. Optical Coherence Tomography and Raman Spectroscopy of the retina

    Evans, J W; Zawadzki, R J; Liu, R; Chan, J; Lane, S; Werner, J S


    Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combining these imaging modalities. We present an ex vivo OCT microscope combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. The combined instrument will be used to investigate remaining technical challenges to combine these imaging modalities, such as the laser power levels needed to achieve a Raman signal above the noise level without damaging the sample.

  16. [Cataract extraction and blue light--impact on the retina].

    Engelmann, K; Funk, R H


    This review focuses on the scientific background for the use of "yellow artificial lenses". We will address the fact that numerous basic scientific publications point to a rationale for this practice although it is often difficult to derive clear-cut evidence from clinical epidemiological studies for the preventive use of yellow artificial lenses. In the first part we refer to studies showing that especially the shortwave part of the visible spectrum of light can be harmful for the retina and optic nerve. For this, we have screened the literature for the major sources of radical production and for the targets of oxidative stress after impingement of "blue light" on the retina. Furthermore, we can show that many studies in cell and molecular biology, animal experiments and first clinical trials point to a preferential use of yellow-tinted lenses especially in the elderly and AMD patients.

  17. Modeling and Simulation of Microelectrode-Retina Interactions

    Beckerman, M


    The goal of the retinal prosthesis project is the development of an implantable microelectrode array that can be used to supply visually-driven electrical input to cells in the retina, bypassing nonfunctional rod and cone cells, thereby restoring vision to blind individuals. This goal will be achieved through the study of the fundamentals of electrical engineering, vision research, and biomedical engineering with the aim of acquiring the knowledge needed to engineer a high-density microelectrode-tissue hybrid sensor that will restore vision to millions of blind persons. The modeling and simulation task within this project is intended to address the question how best to stimulate, and communicate with, cells in the retina using implanted microelectrodes.

  18. Genetic variations strongly influence phenotypic outcome in the mouse retina.

    Austin S Jelcick

    Full Text Available Variation in genetic background can significantly influence the phenotypic outcome of both disease and non-disease associated traits. Additionally, differences in temporal and strain specific gene expression can also contribute to phenotypes in the mammalian retina. This is the first report of microarray based cross-strain analysis of gene expression in the retina investigating genetic background effects. Microarray analyses were performed on retinas from the following mouse strains: C57BL6/J, AKR/J, CAST/EiJ, and NOD.NON-H2(-nb1 at embryonic day 18.5 (E18.5 and postnatal day 30.5 (P30.5. Over 3000 differentially expressed genes were identified between strains and developmental stages. Differential gene expression was confirmed by qRT-PCR, Western blot, and immunohistochemistry. Three major gene networks were identified that function to regulate retinal or photoreceptor development, visual perception, cellular transport, and signal transduction. Many of the genes in these networks are implicated in retinal diseases such as bradyopsia, night-blindness, and cone-rod dystrophy. Our analysis revealed strain specific variations in cone photoreceptor cell patterning and retinal function. This study highlights the substantial impact of genetic background on both development and function of the retina and the level of gene expression differences tolerated for normal retinal function. These strain specific genetic variations may also be present in other tissues. In addition, this study will provide valuable insight for the development of more accurate models for human retinal diseases.

  19. Immunohistochemical and calcium imaging methods in wholemount rat retina.

    Sargoy, Allison; Barnes, Steven; Brecha, Nicholas C; Pérez De Sevilla Müller, Luis


    In this paper we describe the tools, reagents, and the practical steps that are needed for: 1) successful preparation of wholemount retinas for immunohistochemistry and, 2) calcium imaging for the study of voltage gated calcium channel (VGCC) mediated calcium signaling in retinal ganglion cells. The calcium imaging method we describe circumvents issues concerning non-specific loading of displaced amacrine cells in the ganglion cell layer.

  20. Immunohistochemical and Calcium Imaging Methods in Wholemount Rat Retina

    SARGOY, ALLISON; Barnes, Steven; Brecha, Nicholas C.; De Sevilla Müller, Luis Pérez


    In this paper we describe the tools, reagents, and the practical steps that are needed for: 1) successful preparation of wholemount retinas for immunohistochemistry and, 2) calcium imaging for the study of voltage gated calcium channel (VGCC) mediated calcium signaling in retinal ganglion cells. The calcium imaging method we describe circumvents issues concerning non-specific loading of displaced amacrine cells in the ganglion cell layer.

  1. Effects and Responses to Spaceflight in the Mouse Retina

    Zanello, Susana B.; Theriot, Corey; Westby, Christian; Boyle, Richard


    Several stress environmental factors are combined in a unique fashion during spaceflight, affecting living beings widely across their physiological systems. Recently, attention has been placed on vision changes in astronauts returning from long duration missions. Alterations include hyperoptic shift, globe flattening, choroidal folds and optic disc edema, which are probably associated with increased intracranial pressure. These observations justify a better characterization of the ocular health risks associated with spaceflight. This study investigates the impact of spaceflight on the biology of the mouse retina. Within a successful tissue sharing effort, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (Animal Enclosure Module) mice were used as ground controls. Oxidative stress-induced DNA damage was higher in the flight samples compared to controls on R+1, and decreased on R+7. A trend toward higher oxidative and cellular stress response gene expression was also observed on R+1 compared to AEM controls, and these levels decreased on R+7. Several genes coding for key antioxidant enzymes, namely, heme-oxygenase-1, peroxiredoxin, and catalase, were among those upregulated after flight. Likewise, NF B and TGFbeta1, were upregulated in one flight specimen that overall showed the most elevated oxidative stress markers on R+1. In addition, retinas from vivarium control mice evidenced higher oxidative stress markers, NF B and TGFbeta1, likely due to the more intense illumination in vivarium cages versus the AEM. These preliminary data suggest that spaceflight represents a source of environmental stress that translates into oxidative and cellular stress in the retina, which is partially reversible upon return to Earth. Further work is needed to dissect the contribution of the various spaceflight factors (microgravity, radiation) and to

  2. Analysis of bipolar and amacrine populations in marmoset retina.

    Weltzien, Felix; Percival, Kumiko A; Martin, Paul R; Grünert, Ulrike


    About 15 parallel ganglion cell pathways transmit visual signals to the brain, but the interneuron (bipolar and amacrine) populations providing input to ganglion cells remain poorly understood in primate retina. We carried out a quantitative analysis of the inner nuclear layer in the retina of the marmoset (Callithrix jacchus). Vertical Vibratome sections along the horizontal meridian were processed with immunohistochemical markers. Image stacks were taken with a confocal microscope, and densities of cell populations were determined. The density of flat midget bipolar cells fell from 15,746 cells/mm(2) at 1 mm (8 deg) to 7,827 cells/mm(2) at 3 mm (25 deg). The rod bipolar cell density fell from 8,640 cells/mm(2) at 1 mm to 4,278 cells/mm(2) at 3 mm, but the ratio of the two bipolar cell types did not change with eccentricity. The amacrine cell density ranged from 30,000 cells/mm(2) at 8 deg to less than 15,000 cells/mm(2) at 25 deg, but throughout the retina, the ratio of glycinergic to γ-aminobutyric acid (GABA)ergic to amacrine cells remained relatively constant. The fractions of rod bipolar, cone bipolar, amacrine, Müller, and horizontal cells of all cells in the inner nuclear layer were comparable in central and peripheral retina. Marmosets had lower proportions of midget bipolar and rod bipolar in comparison with macaque. These differences were correlated with differences in rod and cone densities between the two species and did not reflect fundamental differences in the wiring between the two species.

  3. Electroretinogram and Histopathologic Changes of the Retina after Methanol Intoxication

    CHEN Jie-min; ZHU Guang-you; ZHAO Zi-qin; XIA Wen-tao


    In order to study the functional and structural alterations of the retina in SD rat model after methanol intoxication,35 rats were divided randomly into five groups administrated with saline,3-day high dose,7-day high dose,3-day low dose and 7-day low dose methanol separately.The retinal function of each group was assessed by flash electroretinogram (F-ERG) 3 and 7 days after methanol poisoning.The microstructure and ultrastructure of the retina were observed at the same time.The high-dose methanol intoxication induced irreversible retinal functional and structural damages 3 days after poisoning,which included prolonged latency and reduced amplitude of the Max-reaction of F-ERG.These injuries were aggravated 7 days after poisoning.Meanwhile,the latency and amplitude of the Cone-reaction of F-ERG were also affected 3 days after poisoning,but there were no further worsening tendency 7 days after poisoning.The retinal histological analysis showed cellular edema,heteromorphy and disarrangement,tissular loosen of the inner nuclear layer and photoreceptors layer.The mitochondrial damage began at the photoreceptors layer and developed further into the inner nuclear layer.The low-dose methanol intoxication only caused transient damage of the retina.Our results showed that the function and structure of the photoreceptor and inner nuclear layer were the primary target of methanol intoxication and that the rod cells were more sensitive to methanol intoxication than the cone cells.The mitochondrial damage developed from outer layer to inner layer of the retina.

  4. Effect of intensive laser irradiation on lipid peroxidation in retina

    Lyakhnovich, G.V.; Guseynov, T.M.; Zheltov, G.I.; Glazkov, V.N.; Naumovich, A.S.; Koney, S.V.; Volotovskiy, I.D.


    A study was made of the effect of intensive laser irradiation on the kinetics of lipid peroxidation in the retina in in vivo and in vitro conditions and also considered the possible influence on these processes of vitamin E and selenium, which have endogenous antioxidants and play an active part in the regulation of the oxidizing processes in membranes was considered. Tests in vitro were conducted on preparations of bovine eyes; in vivo studies were conducted on Chinchilla rabbits.

  5. Reflectance imaging of the human retina at 810 nm does not suffice to optimize the parameters of hydrodynamic rebalancing laser treatment

    Piffaretti, Filippo; Ballini, Jean-Pierre; Perotti, Roberto; Zellweger, Matthieu; Vezzola, Edoardo; Sickenberg, Michel; Wagnières, Georges


    The hydrodynamic rebalancing laser (HRL) procedure is an ophthalmic therapy based on the administration of subthreshold infrared (810 nm) laser light to selected areas on the retina to treat various retina diseases. Heterogeneities of tissue response are observed, including undesired retinal damages. Variations of tissue absorbance were hypothesized to cause this uneven response. Irradiation parameters (diameter=100 μm power=1 W; irradiation time: 50 to 200 ms), location and tissue response were studied in 16 patients (20 eyes, 2535 laser spots) to discover any correlation between tissue response and normalized fundus reflectance at 810 nm. The results demonstrate a complex relationship between some pathologies and occurrences of retinal damage, but no clear correlation. One possible reason is that the resolution of reflectance images is insufficient to see "small" (40 μm or less) absorption centers, particularly deep-seated ones. Additionally, tissue parameters other than variations of the fundus optical absorption influence heat diffusion and temperature increases. Monitoring or individualizing the light dose in HRL therapy, or any similar infrared diode laser-based therapy will require more sophisticated technologies, including imaging the retina's reflectance with an improved resolution, as well as refined methods to detect complex correlations between retinal damage and specific pathologies.

  6. In vivo intrinsic optical signal imaging of mouse retinas

    Wang, Benquan; Yao, Xincheng


    Intrinsic optical signal (IOS) imaging is a promising noninvasive method for advanced study and diagnosis of eye diseases. Before pursuing clinical applications, more IOS studies employing animal models are necessary to establish the relationship between IOS distortions and eye diseases. Ample mouse models are available for investigating the relationship between IOS distortions and eye diseases. However, in vivo IOS imaging of mouse retinas is challenging due to the small ocular lens (compared to frog eyes) and inevitable eye movements. We report here in vivo IOS imaging of mouse retinas using a custom-designed functional OCT. The OCT system provided high resolution (3 μm) and high speed (up to 500 frames/s) imaging of mouse retinas. An animal holder equipped with a custom designed ear bar and bite bar was used to minimize eye movement due to breathing and heartbeats. Residual eye movement in OCT images was further compensated by accurate image registration. Dynamic OCT imaging revealed rapid IOSs from photoreceptor outer segments immediately (IOS changes were also observed from inner retinal layers with delayed time courses compared to that of photoreceptor IOSs.



    Objective To observe the effects of tetramethyipyrazine(TMP) on retina to find out whether it can protect retina from glaucomatous damage. Methods Twenty-four rabbits were randomly divided into four groups. One eye of each rabbit was model eye induced by 2% methylcellulous, and the other was control eye. Normal saline, TMP, timolol and a combination of timolol and TMP were administrated to group A, B, C and D respectively. At the end of 4th week, eyes were excavated for light and electron microscopic study. Results The numbers of ganglion cells (P <0. 01) and bipolar cells (P <0. 01) in model eye were different significantly between group A and B. In group A, the model eye ganglion cells were karyopyknosis, chromatin margination and nuclear membrane rupture; some in ner nuclear cells dcveloped marked lytic changes; outer segment appeared disorganized; but group B changed slight ly. Conclusion The results suggest that TMP may protect retina from glaucomatous damage.

  8. Light pollution: the possible consequences of excessive illumination on retina.

    Contín, M A; Benedetto, M M; Quinteros-Quintana, M L; Guido, M E


    Light is the visible part of the electromagnetic radiation within a range of 380-780 nm; (400-700 on primates retina). In vertebrates, the retina is adapted to capturing light photons and transmitting this information to other structures in the central nervous system. In mammals, light acts directly on the retina to fulfill two important roles: (1) the visual function through rod and cone photoreceptor cells and (2) non-image forming tasks, such as the synchronization of circadian rhythms to a 24 h solar cycle, pineal melatonin suppression and pupil light reflexes. However, the excess of illumination may cause retinal degeneration or accelerate genetic retinal diseases. In the last century human society has increased its exposure to artificial illumination, producing changes in the Light/Dark cycle, as well as in light wavelengths and intensities. Although, the consequences of unnatural illumination or light pollution have been underestimated by modern society in its way of life, light pollution may have a strong impact on people's health. The effects of artificial light sources could have direct consequences on retinal health. Constant exposure to different wavelengths and intensities of light promoted by light pollution may produce retinal degeneration as a consequence of photoreceptor or retinal pigment epithelium cells death. In this review we summarize the different mechanisms of retinal damage related to the light exposure, which generates light pollution.

  9. Meduloepitelioma teratóide da retina: relato de caso Teratoid medulloepithelioma of the retina: case report

    Ramon Coral Ghanem


    Full Text Available O meduloepitelioma é um tumor intra-ocular congênito originário do epitélio medular primitivo que, por sua vez, é responsável pela formação do epitélio não pigmentado do corpo ciliar. Ocorre geralmente na infância, de forma unilateral, acometendo o corpo ciliar. O objetivo deste trabalho é documentar um caso raro de meduloepitelioma teratóide originário da retina. Paciente de nove anos, feminina, apresentava baixa acuidade visual (AV, estrabismo e leucocoria no olho esquerdo (OE. A AV era de 1,0 no olho direito e movimentos de mão no OE. Foi observada tumoração retrocristaliniana branco-acinzentada no OE, aparentemente subretiniana, vascularizada, de grande extensão, com alterações císticas na sua superfície. Foram realizadas tomografia de crânio e órbitas e ecografia ocular. A paciente foi submetida à enucleação com suspeita clínica de retinoblastoma. Pelo aspecto histopatológico foi feito o diagnóstico de meduloepitelioma teratóide benigno originário da retina. Na maioria dos casos apresentados na literatura o meduloepitelioma tem origem a partir do epitélio não pigmentado do corpo ciliar. No nosso caso, a neoplasia parece ter tido origem a partir da retina, já que os cortes revelaram epitélio do corpo ciliar preservado e não foi reconhecida a estrutura normal da retina. Embora o tumor apresentado neste relato tenha sido classificado como benigno, o fato de ser lesão de grandes proporções e de crescimento aparentemente recente, justifica a conduta cirúrgica empregada. O tratamento do meduloepitelioma deve objetivar a intervenção cirúrgica precoce, na tentativa de se evitar a disseminação extra-ocular.Medulloepithelioma is a congenital intraocular tumor that usually arises from the primitive medullary epithelium that is destined to form the nonpigmented ciliary epithelium of the ciliary body. It occurs most frequently in early childhood and is unilateral. This report documents a rare case of

  10. Investigation of consumer satisfaction with cognitive-behaviour therapy and sertraline in the treatment of adolescent depression.

    Dudley, Amanda L; Melvin, Glenn A; Williams, Nicola J; Tonge, Bruce J; King, Neville J


    A new instrument, the Adolescent Depression Treatment Satisfaction Questionnaire (ADTSQ) was devised to measure the consumer satisfaction of depressed adolescents and their parents. The objectives of the paper were to present the psychometric properties of the ADTSQ and to investigate the relative consumer satisfaction with cognitive-behavioural therapy (CBT), sertraline (SRT) and a combined treatment of CBT and SRT (COMBINED) for the treatment of adolescent depression. In addition, participants were asked to rank their most preferred treatment from the following approaches: medication, individual counselling, group program and family therapy. Thirty-eight adolescents with a unipolar depressive disorder and 37 parents who participated in a randomized clinical trial of CBT versus SRT versus COMBINED completed the ADTSQ following the completion of acute treatment. The ADTSQ was found to have high internal consistency and exploratory factor analysis detected three underlying factors. High levels of consumer satisfaction were reported by both adolescents and parents in all three treatments. Those treated with CBT treatments reported higher levels of skill acquisition than those treated with SRT. Of the four treatment approaches, most parents and adolescents rated individual counselling as their first preference. The ADTSQ is a useful measure of consumer satisfaction for depressed adolescents and their parents. CBT, SRT and COMBINED were shown to have high consumer satisfaction with CBT's higher skills training content reflected in the participants' reports. Individual counselling was perceived as the most favourable choice of treatment for adolescent depression. Although limitations associated with the measurement of consumer satisfaction and of the study are acknowledged, it is recommended that the inclusion of consumer satisfaction measures be considered in clinical trials that examine treatment efficacy.

  11. An approach for online evaluations of dose consequences caused by small rotational setup errors in intracranial stereotactic radiation therapy

    Lu Bo; Li, Jonathan; Kahler, Darren; Yan Guanghua; Mittauer, Kathryn; Shi Wenyin; Okunieff, Paul; Liu, Chihray [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida 32607 (United States)


    Purpose: The purpose of this work is to investigate the impact of small rotational errors on the magnitudes and distributions of spatial dose variations for intracranial stereotactic radiotherapy (SRT) treatment setups, and to assess the feasibility of using the original dose map overlaid with rotated contours (ODMORC) method as a fast, online evaluation tool to estimate dose changes (using DVHs) to clinical target volumes (CTVs) and organs-at-risks (OARs) caused by small rotational setup errors. Methods: Fifteen intracranial SRT cases treated with either three-dimensional conformal radiation therapy (3DCRT) or intensity-modulated radiation therapy (IMRT) techniques were chosen for the study. Selected cases have a variety of anatomical dimensions and pathologies. Angles of {+-}3 deg. and {+-}5 deg. in all directions were selected to simulate the rotational errors. Dose variations in different regions of the brain, CTVs, and OARs were evaluated to illustrate the various spatial effects of dose differences before and after rotations. DVHs accounting for rotations that were recomputed by the treatment planning system (TPS) and those generated by the ODMORC method were compared. A framework of a fast algorithm for multicontour rotation implemented by ODMORC is introduced as well. Results: The average values of relative dose variations between original dose and recomputed dose accounting for rotations were greater than 4.0% and 10.0% in absolute mean and in standard deviation, respectively, at the skull and adjacent regions for all cases. They were less than 1.0% and 2.5% in absolute mean and in standard deviation, respectively, for dose points 3 mm away from the skull. The results indicated that spatial dose to any part of the brain organs or tumors separated from the skull or head surface would be relatively stable before and after rotations. Statistical data of CTVs and OARs indicate the lens and cochleas have the large dose variations before and after rotations

  12. Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

    Goda, Jayant S. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Massey, Christine [Department of Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Kuruvilla, John [Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Keating, Armand; Crump, Michael [Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Tsang, Richard W., E-mail: [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)


    Purpose: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Patients and Methods: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). Results: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). Conclusion: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.

  13. Müller cells express the cannabinoid CB2 receptor in the vervet monkey retina

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian


    The presence of the cannabinoid receptor type 1 (CB1R) has been largely documented in the rodent and primate retinae in recent years. There is, however, some controversy concerning the presence of the CB2 receptor (CB2R) within the central nervous system. Only recently, CB2R has been found...... in the rodent retina, but its presence in the primate retina has not yet been demonstrated. The aim of this study was twofold: 1) to characterize the distribution patterns of CB2R in the monkey retina and compare this distribution with that previously reported for CB1R and 2) to resolve the controversy...... on the presence of CB2R in the neural component of the retina. We therefore thoroughly examined the cellular localization of CB2R in the vervet monkey (Chlorocebus sabeus) retina, using confocal microscopy. Our results demonstrate that CB2R, like CB1R, is present throughout the retinal layers, but with striking...

  14. A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys

    Bouskila, Joseph; Javadi, Pasha; Elkrief, Laurent


    The endocannabinoid (eCB) system is widely expressed in various parts of the central nervous system, including the retina. The localization of the key eCB receptors, particularly CB1R and CB2R, has been recently reported in rodent and primate retinas with striking interspecies differences. Little...... is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system in the retina of mice, tree shrews, and monkeys. We found that CB1R and FAAH distributions are well...... of the outer retina and in retinal neurons of the inner retina; in monkeys, CB2R is restricted to Müller cells. Finally, the expression patterns of MAGL and DAGLα are differently expressed across species. Overall, these results provide evidence that the eCB system is differently expressed in the retina...

  15. Brain derived neurotrophic factor in the retina of the teleost N. furzeri.

    Gatta, Claudia; Castaldo, Luciana; Cellerino, Alessandro; de Girolamo, Paolo; Lucini, Carla; D'Angelo, Livia


    BDNF plays an important role in the development and maintenance of visual circuitries in the retina and brain visual centers. In adulthood, BDNF signaling is involved in neural protection and regeneration of retina. In this survey, we investigated the expression of BDNF in the retina of adult Nothobranchius furzeri, a teleost fish employed for age research. After describing the retina of N. furzeri and confirming that the structure is organized in layers as in all vertebrates, we have studied the localization of BDNF mRNA and protein throughout the retinal layers. BDNF mRNA is detectable in all layers, whereas the protein is lacking in the photoreceptors. The occurrence of BDNF provides new insights on its role in the retina, particularly in view of age-related disease of retina.

  16. MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics.

    Lawrence, Jean M; Singhal, Shweta; Bhatia, Bhairavi; Keegan, David J; Reh, Thomas A; Luthert, Philip J; Khaw, Peng T; Limb, Gloria Astrid


    Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown that Müller cells exhibit progenitor characteristics in the postnatal chick and rat retinae, their progenitor-like role in developed human retina is unknown. We first reported the Müller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors. Since immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. Cells were grown as adherent monolayers, responded to epidermal growth factor, and could be expanded indefinitely without growth factors under normal culture conditions. They could be frozen and thawed without losing their characteristics. In the presence of extracellular matrix and fibroblast growth factor-2 or retinoic acid, they acquired neural morphology, formed neurospheres, and expressed neural stem cell markers including betaIII tubulin, Sox2, Pax6, Chx10, and Notch 1. They also expressed markers of postmitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into the subretinal space of dystrophic Royal College of Surgeons rats or neonatal Lister hooded rats, immortalized cells migrated into the retina, where they expressed various markers of retinal neurons. These observations indicate that adult human neural retina harbors a population of cells that express both Müller glial and stem cell markers and suggest that these cells may have potential use for cell-based therapies to restore retinal function. Disclosure of potential conflicts of interest is found at the end of this article.

  17. Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Reduce Reactive Gliosis and Improve Angiostatin Levels in Retina of Diabetic Rats.

    Guzyk, Mykhailo M; Tykhomyrov, Artem A; Nedzvetsky, Victor S; Prischepa, Irina V; Grinenko, Tatiana V; Yanitska, Lesya V; Kuchmerovska, Tamara M


    Diabetic retinopathy (DR) is a multifactorial disease characterized by reactive gliosis and disbalance of angiogenesis regulators, contributing to endothelial dysfunction and microvascular complications. This study was organized to elucidate whether poly(ADP-ribose) polymerase-1 (PARP-1) inhibition could attenuate diabetes-induced damage to macroglia and correct angiogenic disbalance in diabetic rat retina. After 8 weeks of streptozotocin (STZ)-induced diabetes, Wistar male rats were treated with PARP-1 inhibitors, nicotinamide (NAm) or 3-aminobenzamide (3-AB) (100 and 30 mg/kg/daily i.p., respectively), for 14 days. After the 10-weeks experiment period, retinas were undergone an immunohistochemical staining for glial fibrillary acidic protein (GFAP), while western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of PARP-1, poly(ADP-ribosyl)ated proteins (PARs), GFAP, and angiostatin isoforms. Diabetes induced significant up-regulation and activation of retinal PARP-1, reactive gliosis development, and GFAP overexpression compared to non-diabetic control. Moreover, extensive fragmentation of both PARP-1 and GFAP (hallmarks of apoptosis and macroglia reactivation, respectively) in diabetic retina was also observed. Levels of angiostatin isoforms were dramatically decreased in diabetic retina, sustaining aberrant pro-angiogenic condition. Both NAm and 3-AB markedly attenuated damage to macroglia, evidenced by down-regulation of PARP-1, PARs and total GFAP compared to diabetic non-treated group. PARP-1-inhibitory therapy prevented formation of PARP-1 and GFAP cleavage-derived products. In retinas of anti-PARP-treated diabetic animals, partial restoration of angiostatin's levels was shown. Therefore, PARP-1 inhibitors counteract diabetes-induced injuries and manifest retinoprotective effects, including attenuation of reactive gliosis and improvement of angiogenic status, thus, such agents could be considered as promising candidates for DR

  18. Localization and regulation of dopamine receptor D4 expression in the adult and developing rat retina

    Klitten, Laura L; Rath, Martin F; Coon, Steven L


    Levels of dopamine and melatonin exhibit diurnal rhythms in the rat retina. Dopamine is high during daytime adapting the retina to light, whereas melatonin is high during nighttime participating in the adaptation of the retina to low light intensities. Dopamine inhibits the synthesis of melatonin....... The sharp increase of Drd4 expression at a specific postnatal time suggests that dopamine is involved in retinal development....

  19. Simulation and performance of an artificial retina for 40 MHz track reconstruction


    We present the results of a detailed simulation of the artificial retina pattern-recognition algorithm, designed to reconstruct events with hundreds of charged-particle tracks in pixel and silicon detectors at LHCb with LHC crossing frequency of $40\\,\\rm MHz$. Performances of the artificial retina algorithm are assessed using the official Monte Carlo samples of the LHCb experiment. We found performances for the retina pattern-recognition algorithm comparable with the full LHCb reconstruction ...

  20. Circadian organization of the rodent retina involves strongly coupled, layer-specific oscillators.

    Jaeger, Catherine; Sandu, Cristina; Malan, André; Mellac, Katell; Hicks, David; Felder-Schmittbuhl, Marie-Paule


    Rhythmic physiology is central to retinal function and survival and adapts vision to daily light intensity changes. Mammalian retina rhythmically releases melatonin when cultured under constant conditions, and the occurrence of clock gene [e.g., Period (Per)] expression has been shown for most cellular layers. However, contribution of the distinct layers to genesis of circadian rhythms within the retina is still debated. To characterize their endogenous oscillatory capacity and their communication at the whole-tissue level, we used a vibratome-based method to isolate individual or paired retina cellular layers from the mPer2(Luc) mouse and Per1-luciferase (Per1-Luc) rat, and real-time recorded bioluminescence. We report that each layer of the mouse retina harbors a self-sustained oscillator whose period is significantly longer (∼ 26 hours) than in whole-retina explants (∼ 22.9 hours), indicating that the period is correlated with the degree of coupling. Accordingly, the maximal period (∼ 29 hours) is reached upon complete enzymatic dissociation of the retina. By using pharmacological approaches, we demonstrate that connection between retina oscillators involves gap junctions but only minor contribution from the main retina neurochemicals. Taken together with results from Per1-Luc rats, these data show that mammalian retina consists of a network of layer-specific oscillators whose period is determined by their connectivity.

  1. Tryptophan hydroxylase and serotonin receptor 1A expression in the retina of the sea lamprey.

    Cornide-Petronio, María Eugenia; Anadón, Ramón; Barreiro-Iglesias, Antón; Rodicio, María Celina


    The dual development of the retina of lampreys is exceptional among vertebrates and offers an interesting EvoDevo (evolutionary developmental biology) model for understanding the origin and evolution of the vertebrate retina. Only a single type of photoreceptor, ganglion cell and bipolar cell are present in the early-differentiated central retina of lamprey prolarvae. A lateral retina appears later in medium-sized larvae (about 3 years after hatching in the sea lamprey), growing and remaining largely neuroblastic until metamorphosis. In this lateral retina, only ganglion cells and optic fibers differentiate in larvae, whereas differentiation of amacrine, horizontal, photoreceptor and bipolar cells mainly takes place during metamorphosis, which gives rise to the adult retina. Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter found in the retina of vertebrates whose synthesis is mediated by the rate-limiting enzyme tryptophan hydroxylase (TPH). TPH is also the first enzyme in the biosynthetic pathways of melatonin in photoreceptor cells. The serotonin 1A receptor (5-HT1A) is a major determinant of the activity of both serotonergic cells and their targets due to its pre- and post-synaptic location. Here, we report the developmental pattern of expression of tph and 5-ht1a transcripts in the sea lamprey retina by means of in situ hybridization. In larvae, strong tph mRNA signal was observed in photoreceptors and putative ganglion cells of the central retina, and in some neuroblasts of the lateral retina. In adults, strong tph expression was observed in bipolar, amacrine and ganglion cells and in photoreceptors. In the prolarval (central) retina, all the differentiated retinal cells expressed 5-ht1a transcripts, which were not observed in undifferentiated cells. In larvae, photoreceptors, bipolar cells and ganglion cells in the central retina, and neuroblasts in the lateral retina, showed 5-ht1a expression. In the adult retina, expression of 5-ht1a transcript

  2. Dual cameras acquisition and display system of retina-like sensor camera and rectangular sensor camera

    Cao, Nan; Cao, Fengmei; Lin, Yabin; Bai, Tingzhu; Song, Shengyu


    For a new kind of retina-like senor camera and a traditional rectangular sensor camera, dual cameras acquisition and display system need to be built. We introduce the principle and the development of retina-like senor. Image coordinates transformation and interpolation based on sub-pixel interpolation need to be realized for our retina-like sensor's special pixels distribution. The hardware platform is composed of retina-like senor camera, rectangular sensor camera, image grabber and PC. Combined the MIL and OpenCV library, the software program is composed in VC++ on VS 2010. Experience results show that the system can realizes two cameras' acquisition and display.

  3. Transplantation of Photoreceptor Precursors Isolated via a Cell Surface Biomarker Panel From Embryonic Stem Cell-Derived Self-Forming Retina.

    Lakowski, Jorn; Gonzalez-Cordero, Anai; West, Emma L; Han, Ya-Ting; Welby, Emily; Naeem, Arifa; Blackford, Samuel J I; Bainbridge, James W B; Pearson, Rachael A; Ali, Robin R; Sowden, Jane C


    Loss of photoreceptors due to retinal degeneration is a major cause of untreatable blindness. Cell replacement therapy, using pluripotent stem cell-derived photoreceptor cells, may be a feasible future treatment. Achieving safe and effective cell replacement is critically dependent on the stringent selection and purification of optimal cells for transplantation. Previously, we demonstrated effective transplantation of post-mitotic photoreceptor precursor cells labelled by fluorescent reporter genes. As genetically labelled cells are not desirable for therapy, here we developed a surface biomarker cell selection strategy for application to complex pluripotent stem cell differentiation cultures. We show that a five cell surface biomarker panel CD73(+)CD24(+)CD133(+)CD47(+)CD15(-) facilitates the isolation of photoreceptor precursors from three-dimensional self-forming retina differentiated from mouse embryonic stem cells. Importantly, stem cell-derived cells isolated using the biomarker panel successfully integrate and mature into new rod photoreceptors in the adult mouse retinae after subretinal transplantation. Conversely, unsorted or negatively selected cells do not give rise to newly integrated rods after transplantation. The biomarker panel also removes detrimental proliferating cells prior to transplantation. Notably, we demonstrate how expression of the biomarker panel is conserved in the human retina and propose that a similar selection strategy will facilitate isolation of human transplantation-competent cells for therapeutic application.

  4. Neurokinin 1 receptor expression in the rat retina.

    Casini, G; Rickman, D W; Sternini, C; Brecha, N C


    Tachykinin (TK) peptides influence neuronal activity in the inner retina of mammals. The aim of this investigation was to determine the cellular localization of the neurokinin 1 receptor (NK1), whose preferred ligand is the TK peptide substance P (SP), in the rat retina. These studies used a polyclonal antiserum directed to the C-terminus of rat NK1. The majority of NK1-immunoreactive (IR) cells were located in the proximal inner nuclear layer (INL), and very rarely they were found in the distal INL. Some small and large NK1-IR somata were present in the ganglion cell layer. NK1-IR processes were densely distributed across the inner plexiform layer (IPL) with a maximum density over lamina 2 of the IPL. Immunoreactive processes also crossed the INL and ramified in the outer plexiform layer where they formed a sparse meshwork. NK1-IR processes were rarely observed in the optic nerve fiber layer. Double-label immunofluorescence studies with different histochemical markers for bipolar cells indicated that NK1 immunoreactivity was not present in bipolar cells. Together, these observations indicate that NK1 immunoreactivity is predominantly expressed by amacrine, displaced amacrine, interplexiform, and some ganglion cells. Double-label immunofluorescence experiments were also performed to characterize NK1-containing amacrine cells. Sixty-one percent of the gamma-aminobutyric acid (GABA)-IR cells, 71% of the large tyrosine hydroxylase (TH)-IR cells, and 100% of the small TH-IR cells contained NK1 immunoreactivity. In addition, most (91%) of the NK1-IR cells had GABA immunoreactivity. In contrast, vasoactive intestinal polypeptide-, TK-, choline acetyltransferase-, and parvalbumin-IR amacrine tells did not express NK1 immunoreactivity. Overall, the present findings suggest that SP acts directly upon several cell populations, including GABA-containing amacrine cells and ganglion cells, to influence visual information processing in the inner retina.

  5. Pbx homeodomain proteins pattern both the zebrafish retina and tectum

    Stout Jennifer


    Full Text Available Abstract Background Pbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Within the hindbrain, Pbx cooperates with Hox proteins to regulate rhombomere segment identity. Pbx cooperates with Eng to regulate midbrain-hindbrain boundary maintenance, and with MyoD to control fast muscle cell differentiation. Although previous results have demonstrated that Pbx is required for proper eye size, functions in regulating retinal cell identity and patterning have not yet been examined. Results Analysis of retinal ganglion cell axon pathfinding and outgrowth in pbx2/4 null embryos demonstrated a key role for pbx genes in regulating neural cell behavior. To identify Pbx-dependent genes involved in regulating retino-tectal pathfinding, we conducted a microarray screen for Pbx-dependent transcripts in zebrafish, and detected genes that are specifically expressed in the eye and tectum. A subset of Pbx-dependent retinal transcripts delineate specific domains in the dorso-temporal lobe of the developing retina. Furthermore, we determined that some Pbx-dependent transcripts also require Meis1 and Gdf6a function. Since gdf6a expression is also dependent on Pbx, we propose a model in which Pbx proteins regulate expression of the growth factor gdf6a, which in turn regulates patterning of the dorso-temporal lobe of the retina. This, in concert with aberrant tectal patterning in pbx2/4 null embryos, may lead to the observed defects in RGC outgrowth. Conclusion These data define a novel role for Pbx in patterning the vertebrate retina and tectum in a manner required for proper retinal ganglion cell axon outgrowth.

  6. Patterns of rod proliferation in deep-sea fish retinae.

    Fröhlich, E; Negishi, K; Wagner, H J


    In a sample of 37 species of deep-sea fish species from the sea floor of the Porcupine Seabight and the Gobal spur (North Atlantic) we investigated the overall structure of the retina with special respect for the organization of rods, their length and their arrangement in multiple banks. Using an immunocytochemical marker for cell proliferation (PCNA) we studied the mechanisms of rod proliferation, and, by means of serial section reconstruction followed their integration into the existing population of rods. Furthermore, in three different species we have observed growth related changes in retinal thickness, rod density and proliferation activity. We found evidence for two different principles for the organization of rods in these deep-sea fish retinae. In the first group of species represented by Nematonurus armatus and Coryphaenoides guentheri we found rods to be rather short (20-30 microns) and arranged in three and more banks. In these species rod proliferation occurred in a single band of cells immediately vitread of the external limiting membrane, thus showing a high degree of spatial and temporal order. In these species, young rods are inserted just sclerad of the external limiting membrane and the older outer segments pushed away from the incoming light towards the back of the eye. This may be linked to a progressive loss of function of the older rods and might represent an alternative mechanism to the disk shedding in other vertebrates. In the second population (e.g. Conocara macroptera, Alepocephalus agassizii) we observed considerably longer rod outer segments (60-80 microns) forming no more than two layers. These retinae had rod precursors arranged in disseminated clusters throughout the outer nuclear layer indicating the lack of clear spatio-temporal order in mitotic activity along with a more statistical pattern of integration of the newly formed outer segments. In our sample of species both populations were of about equal size suggesting that the two

  7. Cellular origin of intrinsic optical signals in the rabbit retina.

    Naderian, A; Bussières, L; Thomas, S; Lesage, F; Casanova, C


    Optical imaging of retinal intrinsic signals is a relatively new method that provides spatiotemporal patterns of retinal activity through activity-dependent changes in light reflectance of the retina. The exact physiological mechanisms at the origin of retinal intrinsic signals are poorly understood and there are significant inter-species differences in their characteristics and cellular origins. In this study, we re-examined this issue through pharmacological dissection of retinal intrinsic signals in the rabbit with simultaneous ERG recordings. Retinal intrinsic signals faithfully reflected retinal activity as their amplitude was strongly associated with stimulation intensity (r(2)=0.85). Further, a strong linear relation was found using linear regression (r(2)=0.98) between retinal intrinsic signal amplitude and the ERG b wave, which suggests common cellular origins. Intravitreal injections of pharmacological agents were performed to isolate the activity of the retina's major cell types. Retinal intrinsic signals were abolished when the photoreceptors' activity was isolated with aspartate, indicative that they are not at the origin of this signal. A small but significant decrease in intrinsic response (20%) was observed when ganglion and amacrine cells' activity was inhibited by TTX injections. The remaining intrinsic responses were abolished in a dose-dependent manner through the inhibition of ON-bipolar cells by APB. Our results indicate that, in rabbits, retinal intrinsic signals reflect stimulation intensity and originate from the inner retina with a major contribution of bipolar cells and a minor one from ganglion or amacrine cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. [Ketamine-induced ultrastructural changes in the retina].

    Magdolina, A


    Alterations of the retina caused by ketamin were studied in experiment. After a 60-minutes monoanaesthesia with ketamin ultrastructural changes were observed on the inner members of receptor cells, in the three nuclear layers and in the layer of nerve fibres. Severe damage to the structure of the Müller's glial cells providing nutrition to neural-elements was also revealed. Three days after the anaesthesia beside the regression of these alterations, glycogen deposits could be seen in the Müller's cells. This phenomenon and some side effects caused by ketamin can be explained by increased utilization of oxygen and relative hypoxia.

  9. Noninvasive optical detection of carotenoid antioxidants in the human retina

    Sharifzadeh, Mohsen

    This dissertation develops laser Raman and fluorescence based spectroscopy for the noninvasive detection of medically important pigments in the human retina. Large-scale epidemiological studies have recently shown that the pigments lutein and zeaxanthin, located in the ˜1 mm diameter macular area of the retina, protect the eye from phototoxic blue light and/or oxidative damage. Resonance Raman spectroscopy (RRS) can detect and monitor macular pigments in intact human eyes quantitatively by recording the Raman scattered light originating from the highly specific stretching vibrations of the pigment molecules' conjugated carbon backbone. This dissertation develops RRS from a spatially averaged measuring approach to spatially resolved imaging. For this purpose, a filter-based Raman imaging setup with speckle-free illumination was constructed that permits detection of macular pigments at physiological concentrations with eye-safe laser excitation levels. Subsequently, RRS images would be obtained from the living human retina. The images demonstrate quantitative as well as micron-scale, spatially resolved RRS detection of the whole macular pigment distribution. The RRS images reveal important physiological details of a subject's macular pigment distribution such as the peaked pigment concentration in the center of the macula, and the rapidly dropping pigment concentration towards the periphery of the macula. As an alternative to direct RRS imaging of macular pigments, this dissertation explores an indirect imaging approach of macular pigments, based on excitation spectroscopy of lipofuscin. A dual-wavelength laser apparatus was constructed that excites the lipofuscin fluorescence at wavelengths inside and outside the spectral range of macular pigment absorption, and that allows one to image the fluorescence intensities in a large section of the retina centered on the macula. Measuring the lipofuscin fluorescence intensities inside and outside the macula area at the two

  10. First Results of an "Artificial Retina" Processor Prototype

    Cenci, Riccardo; Bedeschi, Franco; Marino, Pietro; Morello, Michael J.; Ninci, Daniele; Piucci, Alessio; Punzi, Giovanni; Ristori, Luciano; Spinella, Franco; Stracka, Simone; Tonelli, Diego; Walsh, John


    We report on the performance of a specialized processor capable of reconstructing charged particle tracks in a realistic LHC silicon tracker detector, at the same speed of the readout and with sub-microsecond latency. The processor is based on an innovative pattern-recognition algorithm, called "artificial retina algorithm", inspired from the vision system of mammals. A prototype of the processor has been designed, simulated, and implemented on Tel62 boards equipped with high-bandwidth Altera Stratix III FPGA devices. The prototype is the first step towards a real-time track reconstruction device aimed at processing complex events of high-luminosity LHC experiments at 40 MHz crossing rate.

  11. Instant website optimization for retina displays how-to

    Larson, Kyle J


    Written in an accessible and practical manner which quickly imparts the knowledge you want to know. As a How-to book it will use applied examples and teach you to optimize websites for retina displays. This book is for web designers and developers who are familiar with HTML, CSS, and editing graphics who would like to improve their existing website or their next web project with high-resolution images. You'll need to have a high-definition device to be able to test the examples in this book and a server to upload your code to if you're not developing it on that device.

  12. fMRI of retina-originated phosphenes experienced by patients with Leber congenital amaurosis.

    Manzar Ashtari

    Full Text Available A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI to study activations induced by cortical phosphenes. However, there are no fMRI reports on spontaneous phosphenes originating from the retina and the resulting pattern of cortical activations. We performed fMRI during a reversing checkerboard paradigm in three LCA patients who underwent unilateral gene therapy and reported experiencing frequent phosphene on a daily basis. We observed bilateral cortical activation covering the entire visual cortices when patients reported experiencing phosphenes. In contrast, in the absence of phosphenes, activation was regulated by patient's visual ability and demonstrated improved cortical activation due to gene therapy. These fMRI results illustrate the potential impact of phosphene perception on visual function and they may explain some of the variability that clinicians find in visual function testing in retinal degeneration. Although we did not perform correlations between visual function and phosphenes, we hope data presented here raises awareness of this phenomenon and its potential effect on visual function and the implications for clinical testing. We recommend a thorough history for phosphene experiences be taken in patients with retinal disease who are candidates for gene or molecular therapy. Lastly, these data illustrate the potential power of fMRI as an outcome measure of gene therapy and the negative impact phosphenes may have on vision testing. fMRI has proven to be a sensitive, non-invasive, and reproducible test paradigm for these purposes and can complement

  13. Neurological and histological consequences induced by in vivo cerebral oxidative stress: evidence for beneficial effects of SRT1720, a sirtuin 1 activator, and sirtuin 1-mediated neuroprotective effects of poly(ADP-ribose polymerase inhibition.

    Cindy Gueguen

    Full Text Available Poly(ADP-ribosepolymerase and sirtuin 1 are both NAD(+-dependent enzymes. In vitro oxidative stress activates poly(ADP-ribosepolymerase, decreases NAD(+ level, sirtuin 1 activity and finally leads to cell death. Poly(ADP-ribosepolymerase hyperactivation contributes to cell death. In addition, poly(ADP-ribosepolymerase inhibition restores NAD(+ level and sirtuin 1 activity in vitro. In vitro sirtuin 1 induction protects neurons from cell loss induced by oxidative stress. In this context, the role of sirtuin 1 and its involvement in beneficial effects of poly(ADP-ribosepolymerase inhibition were evaluated in vivo in a model of cerebral oxidative stress induced by intrastriatal infusion of malonate in rat. Malonate promoted a NAD(+ decrease that was not prevented by 3-aminobenzamide, a poly(ADP-ribosepolymerase inhibitor, at 4 and 24 hours. However, 3-aminobenzamide increased nuclear SIRT1 activity/expression ratio after oxidative stress. Malonate induced a neurological deficit associated with a striatal lesion. Both were reduced by 3-aminobenzamide and SRT1720, a sirtuin 1 activator, showing beneficial effects of poly(ADP-ribosepolymerase inhibition and sirtuin 1 activation on oxidative stress consequences. EX527, a sirtuin 1 inhibitor, given alone, modified neither the score nor the lesion, suggesting that endogenous sirtuin 1 was not activated during cerebral oxidative stress. However, its association with 3-aminobenzamide suppressed the neurological improvement and the lesion reduction induced by 3-aminobenzamide. The association of 3-aminobenzamide with SRT1720, the sirtuin 1 activator, did not lead to a better protection than 3-aminobenzamide alone. The present data represent the first demonstration that the sirtuin 1 activator SRT1720 is neuroprotective during in vivo cerebral oxidative stress. Furthermore sirtuin 1 activation is involved in the beneficial effects of poly(ADP-ribosepolymerase inhibition after in vivo cerebral oxidative

  14. SU-E-T-304: Dosimetric Comparison of Cavernous Sinus Tumors: Heterogeneity Corrected Pencil Beam (PB-Hete) Vs. X-Ray Voxel Monte Carlo (XVMC) Algorithms for Stereotactic Radiotherapy (SRT)

    Pokhrel, D; Sood, S; Badkul, R; Jiang, H; Saleh, H; Wang, F [University of Kansas Hospital, Kansas City, KS (United States)


    Purpose: To compare dose distributions calculated using PB-hete vs. XVMC algorithms for SRT treatments of cavernous sinus tumors. Methods: Using PB-hete SRT, five patients with cavernous sinus tumors received the prescription dose of 25 Gy in 5 fractions for planning target volume PTV(V100%)=95%. Gross tumor volume (GTV) and organs at risk (OARs) were delineated on T1/T2 MRI-CT-fused images. PTV (range 2.1–84.3cc, mean=21.7cc) was generated using a 5mm uniform-margin around GTV. PB-hete SRT plans included a combination of non-coplanar conformal arcs/static beams delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000 MU/min) beam. Plans were re-optimized using XVMC algorithm with identical beam geometry and MLC positions. Comparison of plan specific PTV(V99%), maximal, mean, isocenter doses, and total monitor units(MUs) were evaluated. Maximal dose to OARs such as brainstem, optic-pathway, spinal cord, and lenses as well as normal tissue volume receiving 12Gy(V12) were compared between two algorithms. All analysis was performed using two-tailed paired t-tests of an upper-bound p-value of <0.05. Results: Using either algorithm, no dosimetrically significant differences in PTV coverage (PTVV99%,maximal, mean, isocenter doses) and total number of MUs were observed (all p-values >0.05, mean ratios within 2%). However, maximal doses to optic-chiasm and nerves were significantly under-predicted using PB-hete (p=0.04). Maximal brainstem, spinal cord, lens dose and V12 were all comparable between two algorithms, with exception of one patient with the largest PTV who exhibited 11% higher V12 with XVMC. Conclusion: Unlike lung tumors, XVMC and PB-hete treatment plans provided similar PTV coverage for cavernous sinus tumors. Majority of OARs doses were comparable between two algorithms, except for small structures such as optic chiasm/nerves which could potentially receive higher doses when using XVMC algorithm. Special attention may need to be paid on a case

  15. Adenovirally Delivered Brain-derived Neurotrophic Factor to Rat Retina

    Xu Hou; Dan Hu; Yannian Hui


    Purpose: To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus.Methods: Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining, and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA).Results: The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point(P < 0.01 ), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01 ).Conclusion: Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.

  16. Sector mapping method for 3D detached retina visualization.

    Zhai, Yi-Ran; Zhao, Yong; Zhong, Jie; Li, Ke; Lu, Cui-Xin; Zhang, Bing


    A new sphere-mapping algorithm called sector mapping is introduced to map sector images to the sphere of an eyeball. The proposed sector-mapping algorithm is evaluated and compared with the plane-mapping algorithm adopted in previous work. A simulation that maps an image of concentric circles to the sphere of the eyeball and an analysis of the difference in distance between neighboring points in a plane and sector were used to compare the two mapping algorithms. A three-dimensional model of a whole retina with clear retinal detachment was generated using the Visualization Toolkit software. A comparison of the mapping results shows that the central part of the retina near the optic disc is stretched and its edges are compressed when the plane-mapping algorithm is used. A better mapping result is obtained by the sector-mapping algorithm than by the plane-mapping algorithm in both the simulation results and real clinical retinal detachment three-dimensional reconstruction.

  17. TRP channel gene expression in the mouse retina.

    Gilliam, Jared C; Wensel, Theodore G


    In order to identify candidate cation channels important for retinal physiology, 28 TRP channel genes were surveyed for expression in the mouse retina. Transcripts for all TRP channels were detected by RT-PCR and sequencing. Northern blotting revealed that mRNAs for 12 TRP channel genes are enriched in the retina. The strongest signals were observed for TRPC1, TRPC3, TRPM1, TRPM3, and TRPML1, and clear signals were obtained for TRPC4, TRPM7, TRPP2, TRPV2, and TRPV4. In situ hybridization and immunofluorescence revealed widespread expression throughout multiple retinal layers for TRPC1, TRPC3, TRPC4, TRPML1, PKD1, and TRPP2. Striking localization of enhanced mRNA expression was observed for TRPC1 in the photoreceptor inner segment layer, for TRPM1 in the inner nuclear layer (INL), for TRPM3 in the INL, and for TRPML1 in the outer plexiform and nuclear layers. Strong immunofluorescence signal in cone outer segments was observed for TRPM7 and TRPP2. TRPC5 immunostaining was largely confined to INL cells immediately adjacent to the inner plexiform layer. TRPV2 antibodies stained photoreceptor axons in the outer plexiform layer. Expression of TRPM1 splice variants was strong in the ciliary body, whereas TRPM3 was strongly expressed in the retinal pigmented epithelium.

  18. Raman detection of carotenoid pigments in the human retina

    Gellermann, Werner; Ermakov, Igor V.; McClane, Robert W.; Bernstein, Paul S.


    We have used resonance Raman scattering as a novel, non- invasive, in-vivo optical technique to measure the concentration of carotenoid pigment in the human retina. Using argon laser excitation we are able to measure two strong carotenoid resonance Raman signals at 1159 and 1525 wave numbers, respectively. The required laser power levels are within the limits given by safety standards for ocular exposure. Of the approximately ten carotenoid pigment found in normal human serum, the species lutein and zeaxanthin are concentrated in high amounts in the cells of the human macula, which is an approximately 5 mm diameter area of the retina in which the visual acuity is highest. These carotenoids give the macula a characteristic yellow coloration, and it is speculated that these molecules function as filter to attenuate photochemical damage and/or image degradation under bright UV/blue light exposures. In addition, they are thought to act as free-radical scavenging antioxidants. Studies have shown that there may be a link between macular degenerative diseases, the leading cause of blindness in the elderly in the US, and the presence or absence of the carotenoids. We describe an instrument capable of measuring the macular carotenoids in human subjects in a non-invasive, rapid and quantitative way.

  19. Stimulus-Evoked Intrinsic Optical Signals in the Retina: Pharmacologic Dissection Reveals Outer Retinal Origins

    Schallek, Jesse; Kardon, Randy; Kwon, Young; Abramoff, Michael; Soliz, Peter; Ts’o, Daniel


    purpose. To elucidate the anatomic origins of stimulus-evoked intrinsic optical signals in the mammalian retina by using selective pharmacologic blockade of specific retinal layers. methods. Four adult cats were used to investigate the stimulus-evoked intrinsic signals. The retinas were visually s

  20. MPP1 links the Usher protein network and the Crumbs protein complex in the retina.

    Gosens, I.; Wijk, E. van; Kersten, F.F.J.; Krieger, E.; Zwaag, B. van der; Marker, T.; Letteboer, S.J.F.; Dusseljee, S.; Peters, T.; Spierenburg, H.A.; Punte, I.M.; Wolfrum, U.; Cremers, F.P.M.; Kremer, H.; Roepman, R.


    The highly ordered distribution of neurons is an essential feature of a functional mammalian retina. Disruptions in the apico-basal polarity complexes at the outer limiting membrane (OLM) of the retina are associated with retinal patterning defects in vertebrates. We have analyzed the binding repert

  1. A method to determine the mechanical properties of the retina based on an experiment in vivo.

    Qian, Xiuqing; Zhang, Kunya; Liu, Zhicheng


    A method is proposed to determine the mechanical properties of retina based on in vivo experiments and numerical simulations. First, saline water was injected into the anterior chamber of the right eye of a cat to cause acute high intraocular pressure. After the eye was scanned using optical coherence tomography under different acute high intraocular pressures, the images of the retina in vivo were obtained and the thickness of the retina was calculated. Then, the three-dimensional structure of the optic nerve head including the retina and the choroid were reconstructed using image processing technology. Three different material models for the retina and the choroid were taken and the finite element models of the optic nerve head were constructed. Finally, an inverse method was proposed to determine the parameters of a constitutive model of the retina and of the choroid simultaneously. The results showed that the deformation of the retina can be properly simulated taking into consideration the nonlinear elastic properties of the retina and of the choroid.

  2. A comparison of some organizational characteristics of the mouse central retina and the human macula.

    Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S


    Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

  3. Aging Leads to Elevation of O-GlcNAcylation and Disruption of Mitochondrial Homeostasis in Retina

    Lin Zhao


    Full Text Available Retina is particularly susceptible to aging as oxidative damage accumulates within retina, leading to age-related retinal dysfunction or even visual loss. However, the underlying mechanisms still remain obscure and effective therapeutic strategy is urgently in need. Here, we quested for the answer particularly focusing on mitochondrial homeostasis and O-GlcNAcylation in rat retina. By comparing expression of electron transfer chain complexes and key factors in mitochondrial biogenesis and dynamics in retinas of aged and young Sprague-Dawley rats, we found that mitochondrial Complex I, II, IV and V were increased in aged retina with decreased mtTFA and Mfn2. Also, we noticed that p38 and JNK of MAPK signaling were substantially more activated in aged retina, suggesting stress induction. In addition, we found that pan-O-GlcNAcylation was remarkably stronger with lower OGA expression in aged retina. To further elucidate the roles of Mfn2 and O-GlcNAcylation, we employed ARPE-19 cells and found that ATP production, oxygen consumption, and mitochondrial membrane potential were reduced and ROS level was increased by Mfn2 knockdown, while treating with PUGNAc or UDP-GlcNAc heightened oxygen consumption and reduced ROS. Our results suggest disrupted mitochondrial homeostasis may increase oxidative stress; yet enhanced O-GlcNAcylation might defend against oxidative stress and promote mitochondrial respiration in aged retina.

  4. Protein changes in the retina following experimental retinal detachment in rabbits

    Mandal, Nakul; Lewis, Geoffrey P; Fisher, Steven K


    Retinal detachment leads to the widespread cellular remodeling of the retina. The purpose of this study was to identify protein changes that accompany these cellular alterations by comparing the proteomic profiles of sham and experimentally detached rabbit retina. Elucidation of the proteins most...

  5. In vivo cellular visualization of the human retina using optical coherence tomography and adaptive optics

    Olivier, S S; Jones, S M; Chen, D C; Zawadzki, R J; Choi, S S; Laut, S P; Werner, J S


    Optical coherence tomography (OCT) sees the human retina sharply with adaptive optics. In vivo cellular visualization of the human retina at micrometer-scale resolution is possible by enhancing Fourier-domain optical-coherence tomography with adaptive optics, which compensate for the eye's optical aberrations.

  6. Effects of Aging and Anatomic Location on Gene Expression in Human Retina

    Hui eCai


    Full Text Available Objective: To determine the effects of age and topographic location on gene expression in human neural retina.Methods: Macular and peripheral neural retina RNA were isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses.Results: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10 and SFRP2 which are preferably expressed in the periphery. Conclusions: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases.

  7. Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders

    Maria Francisca Coutinho


    Full Text Available Lysosomal storage diseases (LSDs are a group of rare, life-threatening genetic disorders, usually caused by a dysfunction in one of the many enzymes responsible for intralysosomal digestion. Even though no cure is available for any LSD, a few treatment strategies do exist. Traditionally, efforts have been mainly targeting the functional loss of the enzyme, by injection of a recombinant formulation, in a process called enzyme replacement therapy (ERT, with no impact on neuropathology. This ineffectiveness, together with its high cost and lifelong dependence is amongst the main reasons why additional therapeutic approaches are being (and have to be investigated: chaperone therapy; gene enhancement; gene therapy; and, alternatively, substrate reduction therapy (SRT, whose aim is to prevent storage not by correcting the original enzymatic defect but, instead, by decreasing the levels of biosynthesis of the accumulating substrate(s. Here we review the concept of substrate reduction, highlighting the major breakthroughs in the field and discussing the future of SRT, not only as a monotherapy but also, especially, as complementary approach for LSDs.

  8. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina.

    Gonzalez-Cordero, Anai; West, Emma L; Pearson, Rachael A; Duran, Yanai; Carvalho, Livia S; Chu, Colin J; Naeem, Arifa; Blackford, Samuel J I; Georgiadis, Anastasios; Lakowski, Jorn; Hubank, Mike; Smith, Alexander J; Bainbridge, James W B; Sowden, Jane C; Ali, Robin R


    Irreversible blindness caused by loss of photoreceptors may be amenable to cell therapy. We previously demonstrated retinal repair and restoration of vision through transplantation of photoreceptor precursors obtained from postnatal retinas into visually impaired adult mice. Considerable progress has been made in differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor lineages. However, the capability of ESC-derived photoreceptors to integrate after transplantation has not been demonstrated unequivocally. Here, to isolate photoreceptor precursors fit for transplantation, we adapted a recently reported three-dimensional (3D) differentiation protocol that generates neuroretina from mouse ESCs. We show that rod precursors derived by this protocol and selected via a GFP reporter under the control of a Rhodopsin promoter integrate within degenerate retinas of adult mice and mature into outer segment-bearing photoreceptors. Notably, ESC-derived precursors at a developmental stage similar to postnatal days 4-8 integrate more efficiently compared with cells at other stages. This study shows conclusively that ESCs can provide a source of photoreceptors for retinal cell transplantation.

  9. Heterogeneity of glia in the retina and optic nerve of birds and mammals.

    Andy J Fischer

    Full Text Available We have recently described a novel type of glial cell that is scattered across the inner layers of the avian retina [1]. These cells are stimulated by insulin-like growth factor 1 (IGF1 to proliferate, migrate distally into the retina, and up-regulate the nestin-related intermediate filament transition. These changes in glial activity correspond with increased susceptibility of neurons to excitotoxic damage. This novel cell-type has been termed the Non-astrocytic Inner Retinal Glia-like (NIRG cells. The purpose of the study was to investigate whether the retinas of non-avian species contain cells that resemble NIRG cells. We assayed for NIRG cells by probing for the expression of Sox2, Sox9, Nkx2.2, vimentin and nestin. NIRG cells were distinguished from astrocytes by a lack of expression for Glial Fibrilliary Acidic Protein (GFAP. We examined the retinas of adult mice, guinea pigs, dogs and monkeys (Macaca fasicularis. In the mouse retina and optic nerve head, we identified numerous astrocytes that expressed GFAP, S100beta, Sox2 and Sox9; however, we found no evidence for NIRG-like cells that were positive for Nkx2.2, nestin, and negative for GFAP. In the guinea pig retina, we did not find astrocytes or NIRG cells in the retina, whereas we identified astrocytes in the optic nerve. In the eyes of dogs and monkeys, we found astrocytes and NIRG-like cells scattered across inner layers of the retina and within the optic nerve. We conclude that NIRG-like cells are present in the retinas of canines and non-human primates, whereas the retinas of mice and guinea pigs do not contain NIRG cells.

  10. Tgfbi/Bigh3 silencing activates ERK in mouse retina.

    Allaman-Pillet, Nathalie; Oberson, Anne; Bustamante, Mauro; Tasinato, Andrea; Hummler, Edith; Schorderet, Daniel F


    BIGH3 is a secreted protein, part of the extracellular matrix where it interacts with collagen and integrins on the cell surface. BIGH3 can play opposing roles in cancer, acting as either tumor suppressor or promoter, and its mutations lead to different forms of corneal dystrophy. Although many studies have been carried out, little is known about the physiological role of BIGH3. Using the cre-loxP system, we generated a mouse model with disruption of the Bigh3 genomic locus. Bigh3 silencing did not result in any apparent phenotype modifications, the mice remained viable and fertile. We were able to determine the presence of BIGH3 in the retinal pigment epithelium (RPE). In the absence of BIGH3, a transient decrease in the apoptotic process involved in retina maturation was observed, leading to a transient increase in the INL thickness at P15. This phenomenon was accompanied by an increased activity of the pro-survival ERK pathway.

  11. Pixel detectors for use in retina neurophysiology studies

    Cunningham, W; Chichilnisky, E J; Horn, M; Litke, A M; Mathieson, K; McEwan, F A; Melone, J; O'Shea, V; Rahman, M; Smith, K M


    One area of major inter-disciplinary co-operation is between the particle physics and bio-medical communities. The type of large detector arrays and fast electronics developed in laboratories like CERN are becoming used for a wide range of medical and biological experiments. In the present work fabrication technology developed for producing semiconductor radiation detectors has been applied to produce arrays which have been used in neuro-physiological experiments on retinal tissue. We have exploited UVIII, a low molecular weight resist, that has permitted large area electron beam lithography. This allows the resolution to go below that of conventional photolithography and hence the production of densely packed similar to 500 electrode arrays with feature sizes down to below 2 mum. The neural signals from significant areas of the retina may thus be captured.

  12. Visual system based on artificial retina for motion detection.

    Barranco, Francisco; Díaz, Javier; Ros, Eduardo; del Pino, Begoña


    We present a bioinspired model for detecting spatiotemporal features based on artificial retina response models. Event-driven processing is implemented using four kinds of cells encoding image contrast and temporal information. We have evaluated how the accuracy of motion processing depends on local contrast by using a multiscale and rank-order coding scheme to select the most important cues from retinal inputs. We have also developed some alternatives by integrating temporal feature results and obtained a new improved bioinspired matching algorithm with high stability, low error and low cost. Finally, we define a dynamic and versatile multimodal attention operator with which the system is driven to focus on different target features such as motion, colors, and textures.

  13. Label-free nonlinear optical imaging of mouse retina.

    He, Sicong; Ye, Cong; Sun, Qiqi; Leung, Christopher K S; Qu, Jianan Y


    A nonlinear optical (NLO) microscopy system integrating stimulated Raman scattering (SRS), two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) was developed to image fresh mouse retinas. The morphological and functional details of various retinal layers were revealed by the endogenous NLO signals. Particularly, high resolution label-free imaging of retinal neurons and nerve fibers in the ganglion cell and nerve fiber layers was achieved by capturing endogenous SRS and TPEF signals. In addition, the spectral and temporal analysis of TPEF images allowed visualization of different fluorescent components in the retinal pigment epithelium (RPE). Fluorophores with short TPEF lifetime, such as A2E, can be differentiated from other long-lifetime components in the RPE. The NLO imaging method would provide important information for investigation of retinal ganglion cell degeneration and holds the potential to study the biochemical processes of visual cycle in the RPE.

  14. Electrophysiological responses of the mouse retina to 12C ions.

    Sannita, Walter G; Peachey, Neal S; Strettoi, Enrica; Ball, Sherry L; Belli, Francesco; Bidoli, Vittorio; Carozzo, Simone; Casolino, Marco; Di Fino, Luca; Picozza, Piergiorgio; Pignatelli, Vincenzo; Rinaldi, Adele; Saturno, Moreno; Schardt, Dieter; Vazquez, Marcelo; Zaconte, Veronica; Narici, Livio


    Phosphenes ("light flashes") have been reported by most astronauts on space missions and by healthy subjects whose eyes were exposed to ionizing radiation in early experiments in particle accelerators. The conditions of occurrence suggested retinal effects of heavy ions. To develop an in vivo animal model, we irradiated the eyes of anesthetized wild-type mice with repeated bursts of 12C ions delivered under controlled conditions in accelerator. 12C ions evoked electrophysiological retinal mass responses and activated the visual system as indicated by responses recorded from the visual cortex. No retinal immunohistological damage was detected. Mice proved a suitable animal model to study radiation-induced phosphenes in vivo and our findings are consistent with an origin of phosphenes in radiation activating the retina.

  15. IGF-1 Signaling Plays an Important Role in the Formation of Three-Dimensional Laminated Neural Retina and Other Ocular Structures From Human Embryonic Stem Cells.

    Mellough, Carla B; Collin, Joseph; Khazim, Mahmoud; White, Kathryn; Sernagor, Evelyne; Steel, David H W; Lako, Majlinda


    We and others have previously demonstrated that retinal cells can be derived from human embryonic stem cells (hESCs) and induced pluripotent stem cells under defined culture conditions. While both cell types can give rise to retinal derivatives in the absence of inductive cues, this requires extended culture periods and gives lower overall yield. Further understanding of this innate differentiation ability, the identification of key factors that drive the differentiation process, and the development of clinically compatible culture conditions to reproducibly generate functional neural retina is an important goal for clinical cell based therapies. We now report that insulin-like growth factor 1 (IGF-1) can orchestrate the formation of three-dimensional ocular-like structures from hESCs which, in addition to retinal pigmented epithelium and neural retina, also contain primitive lens and corneal-like structures. Inhibition of IGF-1 receptor signaling significantly reduces the formation of optic vesicle and optic cups, while exogenous IGF-1 treatment enhances the formation of correctly laminated retinal tissue composed of multiple retinal phenotypes that is reminiscent of the developing vertebrate retina. Most importantly, hESC-derived photoreceptors exhibit advanced maturation features such as the presence of primitive rod- and cone-like photoreceptor inner and outer segments and phototransduction-related functional responses as early as 6.5 weeks of differentiation, making these derivatives promising candidates for cell replacement studies and in vitro disease modeling.

  16. Axonal synapses utilize multiple synaptic ribbons in the mammalian retina.

    Hong-Lim Kim

    Full Text Available In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

  17. Membrane currents of spiking cells isolated from turtle retina.

    Lasater, E M; Witkovsky, P


    We examined the membrane properties of spiking neurons isolated from the turtle (Pseudemys scripta) retina. The cells were maintained in culture for 1-7 days and were studied with the whole cell patch clamp technique. We utilized cells whose perikaryal diameters were greater than 15 microns since Kolb (1982) reported that ganglion cell perikarya in Pseudemys retina are 13-25 microns, whereas amacrine perikarya are less than 14 microns in diameter. We identified 5 currents in the studied cells: (1) a transient sodium current (INa) blocked by TTX, (2) a sustained calcium current (ICa) blocked by cobalt and enhanced by Bay-K 8644, (3) a calcium-dependent potassium current (IK(Ca)), (4) an A-type transient potassium current (IA) somewhat more sensitive to 4-AP than TEA, (5) a sustained potassium current (IK) more sensitive to TEA than 4-AP. The estimated average input resistance of the cells at -70 mV was 720 +/- 440 M omega. When all active currents were blocked, the membrane resistance between -130 and +20 mV was 2.5 G omega. When examined under current clamp, some cells produced multiple spikes to depolarizing steps of 0.1-0.3 nA, whereas other cells produced only a single spike irrespective of the strength of the current pulse. Most single spikers had an outward current that rose to a peak relatively slowly, whereas multiple spikers tend to have a more rapidly activating outward current. Under current clamp, 4-AP slowed the repolarization phase of the spike thus broadening it, but did not always abolish the ability to produce multiple spikes. TEA induced a depolarized plateau following the initial spike which precluded further spikes. It thus appears that the spiking patterns of the retinal cells are shaped primarily by the kinetics of INa, IK and IA and to a lesser extent by IK(Ca).

  18. Differential changes in retina function with normal aging in humans.

    Freund, Paul R; Watson, Juliane; Gilmour, Gregory S; Gaillard, Frédéric; Sauvé, Yves


    We evaluated the full field electroretinogram (ERG) to assess age-related changes in retina function in humans. ERG recordings were performed on healthy subjects with normal fundus appearance, lack of cataract and 20/20 acuity, aged 20-39 years (n = 27; mean age 25 ± 5, standard deviation), 40-59 years (n = 20; mean 53 ± 5), and 60-82 years (n = 18; mean 69 ± 5). Multiple ERG tests were applied, including light and dark-adapted stimulus-response function, dark adaptation and dynamic of recovery from a single bright flash under dark-adapted conditions. Changes in ERG properties were found in the oldest age group when compared with the two younger age groups. (1) The photopic hill effect was less pronounced. (2) Both photopic a-wave and b-wave amplitudes and implicit times were increased at high stimulus strengths. (3) Dark adaptation time was delayed for pure rod and L/M cone-driven responses, respectively. (4) Dark-adapted a-wave but not b-wave amplitudes were reduced, yielding higher B/A ratios. (5) Dark-adapted a- and b-waves implicit times were prolonged: there was a direct proportional correlation between minimal a-wave implicit times and age. (6) The dynamic of dark current recovery from a bright flash, under dark-adapted conditions, was transiently faster at intervals between 0.9 and 2 s. These results denote that aging of the healthy retina is accompanied by specific functional changes, which must be taken into account to optimally diagnose potential pathologies.

  19. Insulin stimulated-glucose transporter Glut 4 is expressed in the retina.

    Gustavo Sánchez-Chávez

    Full Text Available The vertebrate retina is a very metabolically active tissue whose energy demands are normally met through the uptake of glucose and oxygen. Glucose metabolism in this tissue relies upon adequate glucose delivery from the systemic circulation. Therefore, glucose transport depends on the expression of glucose transporters. Here, we show retinal expression of the Glut 4 glucose transporter in frog and rat retinas. Immunohistochemistry and in situ hybridization studies showed Glut 4 expression in the three nuclear layers of the retina: the photoreceptor, inner nuclear and ganglionar cell layers. In the rat retina immunoprecipitation and Western blot analysis revealed a protein with an apparent molecular mass of 45 kDa. ¹⁴C-glucose accumulation by isolated rat retinas was significantly enhanced by physiological concentrations of insulin, an effect blocked by inhibitors of phosphatidyl-inositol 3-kinase (PI3K, a key enzyme in the insulin-signaling pathway in other tissues. Also, we observed an increase in ³H-cytochalasin binding sites in the presence of insulin, suggesting an increase in transporter recruitment at the cell surface. Besides, insulin induced phosphorylation of Akt, an effect also blocked by PI3K inhibition. Expression of Glut 4 was not modified in retinas of a type 1 diabetic rat model. To our knowledge, our results provide the first evidence of Glut4 expression in the retina, suggesting it as an insulin- responsive tissue.

  20. The efficacy of surfactant replacement therapy in the growth restricted preterm infant: what is the evidence?

    Atul eMalhotra


    Full Text Available Background: Surfactant replacement therapy (SRT is an integral part of management of preterm surfactant deficiency (respiratory distress syndrome, RDS. Its role in the management of RDS has been extensively studied. However its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR has not been systematically studied.Objective: To evaluate the efficacy of exogenous surfactant replacement therapy in the management of preterm IUGR lung disease. Methods: A systematic search of all available randomised clinical trials (RCT of surfactant replacement therapy in preterm IUGR infants was done according to the standard Cochrane collaboration search strategy. Neonatal respiratory outcomes were compared between the preterm IUGR and appropriately-grown for gestational age (AGA preterm infant populations in eligible studies. Results: No study was identified which evaluated the efficacy or responsiveness of exogenous surfactant replacement therapy in preterm IUGR infants as compared to preterm AGA infants. The only study identified through the search strategy used small for gestational age (SGA; defined as less than 10th centile for birth weight as a proxy for IUGR. The RCT evaluated the efficacy or responsiveness of SRT in preterm SGA group as compared to AGA infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary air leaks and days on the ventilator did not differ between both groups. However, the requirement for prolonged nasal CPAP (p< 0.001, supplemental oxygen therapy (p <0.01 and the incidence of bronchopulmonary dysplasia at 28 days and 36 weeks (both p<0.01 was greater in SGA infants. Discussion: There is currently insufficient data available to evaluate the efficacy of SRT in preterm IUGR lung disease. A variety of research strategies will be needed to enhance our understanding of the role and rationale for use of surfactant replacement therapy in preterm

  1. Increased frequency of anti-retina antibodies in asymptomatic patients with chronic t. gondii infection

    Cursino, Sylvia Regina Temer; da Costa, Thaís Boccia; Yamamoto, Joyce Hisae; Meireles, Luciana Regina; Silva, Maria Antonieta Longo Galvão; de Andrade Junior, Heitor Franco


    PURPOSE: To search for anti-retina antibodies that serve as markers for eye disease in uveitis. MATERIALS AND METHODS: Stored sera from patients with uveitis, ocular toxoplasmosis (n = 30) and non-infectious, immune-mediated uveitis (n = 50) and from asymptomatic individuals who were positive (n = 250) and negative (n = 250) for anti-Toxoplasma antibodies were tested. Serum anti-retina IgG was detected by an optimized ELISA using a solid-phase whole human retina extract, bovine S-antigen or interphotoreceptor retinoid-binding protein. RESULTS: Uveitis patients showed a higher mean reactivity to whole human retina extract, interphotoreceptor retinoid-binding protein and S-antigen in comparison to the asymptomatic population. These findings were independent of the uveitis origin and allowed the determination of the lower anti-retina antibody cut-off for the three antigens. Asymptomatic anti-Toxoplasma serum-positive individuals showed a higher frequency of anti-human whole retina extract antibodies in comparison to asymptomatic anti-Toxoplasma serum-negative patients. The bovine S-antigen and interphotoreceptor retinoid-binding protein ELISAs also showed a higher mean reactivity in the uveitis groups compared to the asymptomatic group, but the observed reactivities were lower and overlapped without discrimination. CONCLUSION: We detected higher levels of anti-retina antibodies in uveitis patients and in a small fraction of asymptomatic patients with chronic toxoplasmosis. The presence of anti-retina antibodies in sera might be a marker of eye disease in asymptomatic patients, especially when whole human retina extract is used in a solid-phase ELISA. PMID:21120306

  2. Increased frequency of anti-retina antibodies in asymptomatic patients with chronic t. gondii infection

    Sylvia Regina Temer Cursino


    Full Text Available PURPOSE: To search for anti-retina antibodies that serve as markers for eye disease in uveitis. MATERIALS AND METHODS: Stored sera from patients with uveitis, ocular toxoplasmosis (n = 30 and non-infectious, immune-mediated uveitis (n = 50 and from asymptomatic individuals who were positive (n = 250 and negative (n = 250 for anti-Toxoplasma antibodies were tested. Serum anti-retina IgG was detected by an optimized ELISA using a solid-phase whole human retina extract, bovine S-antigen or interphotoreceptor retinoid-binding protein. RESULTS: Uveitis patients showed a higher mean reactivity to whole human retina extract, interphotoreceptor retinoid-binding protein and S-antigen in comparison to the asymptomatic population. These findings were independent of the uveitis origin and allowed the determination of the lower anti-retina antibody cut-off for the three antigens. Asymptomatic anti-Toxoplasma serum-positive individuals showed a higher frequency of antihuman whole retina extract antibodies in comparison to asymptomatic anti-Toxoplasma serum-negative patients. The bovine S-antigen and interphotoreceptor retinoid-binding protein ELISAs also showed a higher mean reactivity in the uveitis groups compared to the asymptomatic group, but the observed reactivities were lower and overlapped without discrimination. CONCLUSION: We detected higher levels of anti-retina antibodies in uveitis patients and in a small fraction of asymptomatic patients with chronic toxoplasmosis. The presence of anti-retina antibodies in sera might be a marker of eye disease in asymptomatic patients, especially when whole human retina extract is used in a solid-phase ELISA.

  3. Novel features of neurodegeneration in the inner retina of early diabetic rats.

    Énzsöly, Anna; Szabó, Arnold; Szabó, Klaudia; Szél, Ágoston; Németh, János; Lukáts, Ákos


    The literature indicates that in diabetes retinal dysfunctions related to neural retinal alterations exist prior to clinically detectable vasculopathy. In a previous report, a detailed description about the alteration of the outer retina was given, where diabetic degeneration preceded apoptotic loss of cells (Enzsöly et al., 2014). Here, we investigated the histopathology of the inner retina in early diabetes using the same specimens. We examined rat retinas with immunohistochemistry and Western blotting, 12 weeks after streptozotocin induction of diabetes. Glial reactivity was observed in all diabetic retinal specimens; however, it was not detectable all over the retina, but appeared in randomly arranged patches, with little or no glia activation in between. Similarly, immunoreactivity of parvalbumin (staining mostly AII amacrine cells) was also decreased only in some regions. We propose that these focal changes appear prior to affecting the whole retina and overt loss of cells. In contrast to these, most other markers used (calretinin, recoverin, tyrosin hydroxylase anti-Brn-3a and also calbindin in the optic part of the retina) did not show any major alterations in the intensity of immunoreactivity or in the number of stained elements. Interestingly, under diabetic conditions, the labeling pattern of PKC-α and calbindin in the ciliary retina showed a clear resemblance to the pattern described during development. This observation is in line with our previous study, reporting an increase in the number of dual cones, coexpressing two photopigments, which is another common feature with developing retinas. These data may indicate a previously uninvestigated regenerative capacity in diabetic retina.

  4. The role of histamine in the retina: studies on the Hdc knockout mouse.

    Greferath, Ursula; Vessey, Kirstan A; Jobling, Andrew I; Mills, Samuel A; Bui, Bang V; He, Zheng; Nag, Nupur; Ohtsu, Hiroshi; Fletcher, Erica L


    The role of histamine in the retina is not well understood, despite it regulating a number of functions within the brain, including sleep, feeding, energy balance, and anxiety. In this study we characterized the structure and function of the retina in mice that lacked expression of the rate limiting enzyme in the formation of histamine, histidine decarboxylase (Hdc-/- mouse). Using laser capture microdissection, Hdc mRNA expression was assessed in the inner and outer nuclear layers of adult C57Bl6J wildtype (WT) and Hdc(-/-)-retinae. In adult WT and Hdc(-/-)-mice, retinal fundi were imaged, retinal structure was assessed using immunocytochemistry and function was probed by electroretinography. Blood flow velocity was assessed by quantifying temporal changes in the dynamic fluorescein angiography in arterioles and venules. In WT retinae, Hdc gene expression was detected in the outer nuclear layer, but not the inner nuclear layer, while the lack of Hdc expression was confirmed in the Hdc-/- retina. Preliminary examination of the fundus and retinal structure of the widely used Hdc-/- mouse strain revealed discrete lesions across the retina that corresponded to areas of photoreceptor abnormality reminiscent of the rd8 (Crb1) mutation. This was confirmed after genotyping and the strain designated Hdcrd8/rd8. In order to determine the effect of the lack of Hdc-alone on the retina, Hdc-/- mice free of the Crb1 mutation were bred. Retinal fundi appeared normal in these animals and there was no difference in retinal structure, macrogliosis, nor any change in microglial characteristics in Hdc-/- compared to wildtype retinae. In addition, retinal function and retinal blood flow dynamics showed no alterations in the Hdc-/- retina. Overall, these results suggest that histamine plays little role in modulating retinal structure and function.

  5. The role of histamine in the retina: studies on the Hdc knockout mouse.

    Ursula Greferath

    Full Text Available The role of histamine in the retina is not well understood, despite it regulating a number of functions within the brain, including sleep, feeding, energy balance, and anxiety. In this study we characterized the structure and function of the retina in mice that lacked expression of the rate limiting enzyme in the formation of histamine, histidine decarboxylase (Hdc-/- mouse. Using laser capture microdissection, Hdc mRNA expression was assessed in the inner and outer nuclear layers of adult C57Bl6J wildtype (WT and Hdc(-/--retinae. In adult WT and Hdc(-/--mice, retinal fundi were imaged, retinal structure was assessed using immunocytochemistry and function was probed by electroretinography. Blood flow velocity was assessed by quantifying temporal changes in the dynamic fluorescein angiography in arterioles and venules. In WT retinae, Hdc gene expression was detected in the outer nuclear layer, but not the inner nuclear layer, while the lack of Hdc expression was confirmed in the Hdc-/- retina. Preliminary examination of the fundus and retinal structure of the widely used Hdc-/- mouse strain revealed discrete lesions across the retina that corresponded to areas of photoreceptor abnormality reminiscent of the rd8 (Crb1 mutation. This was confirmed after genotyping and the strain designated Hdcrd8/rd8. In order to determine the effect of the lack of Hdc-alone on the retina, Hdc-/- mice free of the Crb1 mutation were bred. Retinal fundi appeared normal in these animals and there was no difference in retinal structure, macrogliosis, nor any change in microglial characteristics in Hdc-/- compared to wildtype retinae. In addition, retinal function and retinal blood flow dynamics showed no alterations in the Hdc-/- retina. Overall, these results suggest that histamine plays little role in modulating retinal structure and function.

  6. Distribution of tubulin, kinesin, and dynein in light- and dark-adapted octopus retinas.

    Martinez, J M; Elfarissi, H; De Velasco, B; Ochoa, G H; Miller, A M; Clark, Y M; Matsumoto, B; Robles, L J


    Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected alpha- and beta-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.

  7. Differential Gene Expression in Retina of Myopic Chicken Eyes Using mRNA Differential Display

    ShenHX; ZhangQJ


    Purpose:To study differentially expressed genes in retina of experimental myopic chicken.Methods:Experimental myopia in chicken was induced by form-deprivatin.The mRNA in chicen retina was analyzed by using differential display.Results:Experimental myopia was successfully induced in chicken through form-deprivation.Differentially expressed gene fragments were detected in retina of chicken with myopic evelopment and recovery as compared with normal controld.Conclusion:The differential display of mRNA may be a useful way in cloning myopic-related genes.

  8. Semiconductor nanorod-carbon nanotube biomimetic films for wire-free photostimulation of blind retinas.

    Bareket, Lilach; Waiskopf, Nir; Rand, David; Lubin, Gur; David-Pur, Moshe; Ben-Dov, Jacob; Roy, Soumyendu; Eleftheriou, Cyril; Sernagor, Evelyne; Cheshnovsky, Ori; Banin, Uri; Hanein, Yael


    We report the development of a semiconductor nanorod-carbon nanotube based platform for wire-free, light induced retina stimulation. A plasma polymerized acrylic acid midlayer was used to achieve covalent conjugation of semiconductor nanorods directly onto neuro-adhesive, three-dimensional carbon nanotube surfaces. Photocurrent, photovoltage, and fluorescence lifetime measurements validate efficient charge transfer between the nanorods and the carbon nanotube films. Successful stimulation of a light-insensitive chick retina suggests the potential use of this novel platform in future artificial retina applications.

  9. Simulation and performance of an artificial retina for 40 MHz track reconstruction

    Abba, A; Citterio, M; Caponio, F; Cusimano, A; Geraci, A; Marino, P; Morello, M J; Neri, N; Punzi, G.; Piucci, A; Ristori, L; Spinella, F; Stracka, S; Tonelli, D


    We present the results of a detailed simulation of the artificial retina pattern-recognition algorithm, designed to reconstruct events with hundreds of charged-particle tracks in pixel and silicon detectors at LHCb with LHC crossing frequency of 40MHz. The detailed geometry and charged-particle activity of a large tracking detector are simulated and used to assess the performance of the artificial retina algorithm. Excellent performances have been found for the retina pattern-recognition algorithm, comparable with the full LHCb reconstruction algorithm.

  10. Dual-path handheld system for cornea and retina imaging using optical coherence tomography

    Shirazi, Muhammad Faizan; Wijesinghe, Ruchire Eranga; Ravichandran, Naresh Kumar; Kim, Pilun; Jeon, Mansik; Kim, Jeehyun


    A dual-path handheld system is proposed for cornea and retina imaging using spectral domain optical coherence tomography. The handheld sample arm is designed to acquire two images simultaneously. Both eyes of a person can be imaged at the same time to obtain the images of the cornea of one eye and the retina of the other eye. Cornea, retina, and optic disc images are acquired with the proposed sample arm. Experimental results demonstrate the usefulness of this system for imaging of different eye segments. This system reduces the time required for imaging of the two eyes and is cost effective.

  11. Structural and molecular analysis of arteriolar annuli in the retina: implications in diabetic and hypertensive retinopathy

    Ramos Gonzalez, David


    La vasculatura de la retina presenta características especiales ya que es fundamental que los vasos no interfieran el paso de la luz, que debe atravesar la retina para llegar a los fotoreceptores. El pequeño calibre de los capilares retinianos, junto con los elevados requerimientos metabólicos, hace que la regulación del flujo sanguíneo sea fundamental para el correcto mantenimiento de la homeostasis de la retina. La vasculatura retiniana no presenta inervación, por lo que la influencia de es...

  12. Nitrification Enhancement in Closed Double-SRT Activated Sludge Process%闭式双泥龄活性污泥工艺强化硝化的中试研究

    刘振; 沈伟; 马寅宗; 丁蓟羽; 吴敏


    A pilot test to evaluate the closed double-SRT activated sludge process in Zhuyuan Second Wastewater Treatment Plant in Shanghai was carried out. The concentrations of COD, NH4+ - N, NO3- - N and TN in the effluent from the ordinary aeration tank, A/O tank and secondary settling tank were determined, and the pollutant removal process and mechanism were analyzed. Furthermore, the mi-crobial community structure was studied using FISH and PCR-DGGE. The results showed that the closed double-SRT activated sludge process was similar to the BABE. In the A/O tank, nitrobacteria were cultivated and transferred to the ordinary aeration tank continuously. The ordinary aeration tank could remove NH4+ - N in a short SRT, thus the nitrification efficiency of the system was enhanced.%模拟上海市竹园第二污水处理厂的闭式双泥龄活性污泥工艺进行中试研究,通过测定普通曝气池、A/O池和二沉池出水中COD、NH4+-N、NO3--N和TN的浓度,分析该工艺的除污过程及机理,并利用荧光原位杂交技术(FISH)和聚合酶链反应—变性梯度凝胶电泳技术(PCR-DGGE)研究了微生物群落结构.结果表明,闭式双泥龄活性污泥工艺类似于侧流富集/主流强化硝化工艺,A/O池相当于普通曝气池的“侧流硝化菌富集池”,它在处理污水的同时不断地培养和富集硝化菌,并通过二沉池连续回流至普通曝气池内,使普通曝气池在低污泥龄条件下仍具有很强的硝化能力,从而强化了系统的硝化效果.

  13. Human retina-specific amine oxidase: genomic structure of the gene (AOC2), alternatively spliced variant, and mRNA expression in retina.

    Imamura, Y; Noda, S; Mashima, Y; Kudoh, J; Oguchi, Y; Shimizu, N


    Previously, we reported the isolation of cDNA for human retina-specific amine oxidase (RAO) and the expression of RAO exclusively in retina. Bacterial artificial chromosome clones containing the human RAO gene (AOC2) were mapped to human chromosome 17q21 (Imamura et al., 1997, Genomics 40: 277-283). Here, we report the complete genomic structure of the RAO gene, including 5' flanking sequence, and mRNA expression in retina. The human RAO gene spans 6 kb and is composed of four exons corresponding to the amino acid sequence 1-530, 530-598, 598-641, and 642-729 separated by three introns of 3000, 310, and 351 bp. Screening of a human retina cDNA library revealed the existence of an alternatively spliced cDNA variant with an additional 81 bp at the end of exon 2. The sizes of exons and the locations of exon/intron boundaries in the human RAO gene showed remarkable similarity to those of the human kidney diamine oxidase gene (AOC1). In situ hybridization revealed that mRNA coding for RAO is expressed preferentially in the ganglion cell layer of the mouse retina. We designed four sets of PCR primers to amplify four exons, which will be valuable for analyzing mutations in patients with ocular diseases affecting the retinal ganglion cell layer.

  14. Symptomatic Outcomes in Relation to Tumor Expansion After Fractionated Stereotactic Radiation Therapy for Vestibular Schwannomas: Single-Institutional Long-Term Experience

    Aoyama, Hidefumi, E-mail: [Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Department of Radiology, Division of Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan); Onodera, Shunsuke [Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takeichi, Norihito [Department of Otolaryngology, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Onimaru, Rikiya [Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Terasaka, Shunsuke; Sawamura, Yutaka [Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Shirato, Hiroki [Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan)


    Purpose: The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. Methods and Materials: This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. Results: The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. Conclusions: Fractionated SRT could be safely applied even for medium- to large-sized ({>=}20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.

  15. Organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro.

    Satoru Moritoh

    Full Text Available BACKGROUND: Organotypic tissue culture of adult rodent retina with an acute gene transfer that enables the efficient introduction of variable transgenes would greatly facilitate studies into retinas of adult rodents as animal models. However, it has been a difficult challenge to culture adult rodent retina. The purpose of this present study was to develop organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We established an interphase organotypic tissue culture for adult rat retinas (>P35 of age which was optimized from that used for adult rabbit retinas. We implemented three optimizations: a greater volume of Ames' medium (>26 mL per retina, a higher speed (constant 55 rpm of agitation by rotary shaker, and a greater concentration (10% of horse serum in the medium. We also successfully applied this method to adult mouse retina (>P35 of age. The organotypic tissue culture allowed us to keep adult rodent retina morphologically and structurally intact for at least 4 days. However, mouse retinas showed less viability after 4-day culture. Electrophysiologically, ganglion cells in cultured rat retina were able to generate action potentials, but exhibited less reliable light responses. After transfection of EGFP plasmids by particle-mediated acute gene transfer, we observed EGFP-expressing retinal ganglion cells as early as 1 day of culture. We also introduced polarized-targeting fusion proteins such as PSD95-GFP and melanopsin-EYFP (hOPN4-EYFP into rat retinal ganglion cells. These fusion proteins were successfully transferred into appropriate locations on individual retinal neurons. CONCLUSIONS/SIGNIFICANCE: This organotypic culture method is largely applicable to rat retinas, but it can be also applied to mouse retinas with a caveat regarding cell viability. This method is quite flexible for use in acute gene transfection in adult rodent retina, replacing

  16. Adjunctive MSCs enhance myelin formation by xenogenic oligodendrocyte precursors transplanted in the retina

    Aileen Arriola; Mary E Kie; Yufang Shi; Randall D McKinnon


    Dear Editor, We examined myelin formation by oligodendrocytes co-transplanted with immunosuppressive mesenchymal stem cells (MSCs). Oligodendrocyte precursor cells (OPCs) were grafted into the mouse retina, and graft survival and maturation was determined with or without adjunctive MSCs.

  17. Diabetes Alters Osmotic Swelling Characteristics and Membrane Conductance of Glial Cells in Rat Retina

    Thomas Pannicke; Ianors Iandiev; Antje Wurm; Ortrud Uckermann; Franziska vom Hagen; Andreas Reichenbach; Peter Wiedemann; Hans-Peter Hammes; Andreas Bringmann


    Diabetes Alters Osmotic Swelling Characteristics and Membrane Conductance of Glial Cells in Rat Retina Thomas Pannicke 1 , Ianors Iandiev 2 , Antje Wurm 2 , Ortrud Uckermann 3 , Franziska vom Hagen 4...

  18. Retina-on-a-chip: a microfluidic platform for point access signaling studies.

    Dodson, Kirsten H; Echevarria, Franklin D; Li, Deyu; Sappington, Rebecca M; Edd, Jon F


    We report on a microfluidic platform for culture of whole organs or tissue slices with the capability of point access reagent delivery to probe the transport of signaling events. Whole mice retina were maintained for multiple days with negative pressure applied to tightly but gently bind the bottom of the retina to a thin poly-(dimethylsiloxane) membrane, through which twelve 100 μm diameter through-holes served as fluidic access points. Staining with toluidine blue, transport of locally applied cholera toxin beta, and transient response to lipopolysaccharide in the retina demonstrated the capability of the microfluidic platform. The point access fluidic delivery capability could enable new assays in the study of various kinds of excised tissues, including retina.

  19. Comparison of dark- and light-adapted carp retinas with NADPH diaphorase staining

    叶冰; 杨雄里


    The carp retina was examined by NADPH diaphorase histochemistry to determine if the staining pattern of retinal cells was changed depending on the adaptation state of the retina. When dark-adapted for 5 h, ellipsoids of inner segments of both rods and cones and some horizontal cells were heavily stained. Staining was also found in subpopulations of amacrine cells and ganglion cells. In addition, Muller cells were strongly positive for NADPH diaphorase. When light-adapted for 5h, ellipsoids of photoreceptors and ganglion cells were less intensely stained, whereas Muller cells and horizontal cells became negative for NADPH diaphorase. Furthermore, rod ON-center bipolar cells were clearly stained. The difference of staining of amacrine cells between dark- and light-adapted retinas was not significant. The differences in diaphorase-staining pattern between dark- and light-adapted retinas suggest that Muller cells, some horizontal cells and rod ON-center bipolar cells contain inducible nitric oxide synthase,

  20. Illumination-invariant face recognition with a contrast sensitive silicon retina

    Buhmann, J.M. [Rheinische Friedrich-Wilhelms-Univ., Bonn (Germany). Inst. fuer Informatik II; Lades, M. [Bochum Univ. (Germany). Inst. fuer Neuroinformatik; Eeckman, F. [Lawrence Livermore National Lab., CA (United States)


    Changes in lighting conditions strongly effect the performance and reliability of computer vision systems. We report face recognition results under drastically changing lighting conditions for a computer vision system which concurrently uses a contrast sensitive silicon retina and a conventional, gain controlled CCD camera. For both input devices the face recognition system employs an elastic matching algorithm with wavelet based features to classify unknown faces. To assess the effect of analog on-chip preprocessing by the silicon retina the CCD images have been digitally preprocessed with a bandpass filter to adjust the power spectrum. The silicon retina with its ability to adjust sensitivity increases the recognition rate up to 50 percent. These comparative experiments demonstrate that preprocessing with an analog VLSI silicon retina generates image data enriched with object-constant features.

  1. Frequency spectrum might act as communication code between retina and visual cortex I

    Xu Yang


    Full Text Available AIM: To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I (V1. METHODS: Fourteen C57BL/6J mice were measured with pattern electroretinogram (PERG and pattern visually evoked potential (PVEP and fast Fourier transform has been used to analyze the frequency components of those signals. RESULTS: The amplitude of PERG and PVEP was measured at about 36.7 µV and 112.5 µV respectively and the dominant frequency of PERG and PVEP, however, stay unchanged and both signals do not have second, or otherwise, harmonic generation. CONCLUSION: The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex. The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1.

  2. Adenosine as a signaling molecule in the retina: biochemical and developmental aspects



    Full Text Available The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity or A2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calcium-dependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation.O nucleosídeo adenosina apresenta um importante papel como neurotransmissor ou neuromodulador no sistema nervoso central, inclusive na retina. Neste artigo apresentamos uma revisão das evidências que mostram que a adenosina é uma molécula sinalizadora na retina em desenvolvimento. Na retina de pinto, transportadores de adenosina estão presentes desde estágios precoces do desenvolvimento, antes do aparecimento dos receptores A1 que modulam a atividade adenilato ciclase dependente de dopamina ou dos receptores A2 que ativam diretamente a enzima. Experimentos usando culturas de células de retina revelaram que a adenosina é captada por populações celulares específicas que, quando estimuladas por despolarização ou por

  3. The lens controls cell survival in the retina: evidence from the blind cavefish Astyanax


    The lens influences retinal growth and differentiation during vertebrate eye development but the mechanisms are not understood. The role of the lens in retinal growth and development was studied in the teleost Astyanax mexicanus, which has eyed surface-dwelling (surface fish) and blind cave-dwelling (cavefish) forms. A lens and laminated retina initially develop in cavefish embryos, but the lens dies by apoptosis. The cavefish retina is subsequently disorganized, apoptotic cells appear, the p...

  4. Rax: Developmental and Daily Expression Patterns in the Rat Pineal Gland and Retina

    Rohde, Kristian; Klein, David C.; Møller, Morten; Rath, Martin F.


    Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is e...

  5. A Study of Histology and Enzymatic Histochemistry on Rabbit's Retina in Acute Ocular Hypertension


    The changes of activities of enzymes relating to energy metabolism in rabbit's retina in acute ocular hypertension were observed. The activities of succinate dehydrogenase and adenosine triphosphatase were found to be reduced, while the activities of the lactatic dehydrognease and glucose-6-phosphatase increased. The results revealed the metabolic disturbance of energy in retina after acute ocular hypertension might be the underlying factors relating to the defects of the functions and structures of the...

  6. Rhodopsin-like immunoreactivity in the 'all cone' retina of the chameleon (Chameleo chameleo).

    Bennis, Mohamed; Molday, Robert S; Versaux-Botteri, Claudine; Repérant, Jacques; Jeanny, Jean-Claude; McDevitt, David S


    Chameleons (Order, Reptilia: Family, Lacertilia) are unique among vertebrates in being able to make independent eye movements. The organisation of their retina, however, closely ressembles that of other diurnal lizards; based on morphological studies, it is typically described as containing only cone photoreceptors. We show here that a subpopulation of the photoreceptors are immunolabelled by an antibody directed against rhodopsin, suggesting the presence of rods. We conclude that in the nonmammalian retina, rods and cones cannot be exclusively distinguished on purely morphological grounds.

  7. Otimização de propriedades mecânicas de misturas ternárias de polipropileno (PP/borracha de etileno-propileno-dieno (EPDM/pó de pneus (SRT sob tração e impacto usando a metodologia da superfície de resposta (MSR Optimization of mechanical properties of polypropylene (PP/ethylene-propylene-diene monomer rubber (EPDM/scrap rubber tire (SRT ternary mixtures under tensile and impact using the response surface methodology (RSM

    Helson M. da Costa


    Full Text Available A metodologia da superfície de resposta (MSR é uma coleção de técnicas estatísticas e matemáticas para desenvolver, melhorar e otimizar processos. Neste estudo, a técnica MSR foi aplicada na investigação do comportamento mecânico de diferentes misturas ternárias de PP/EPDM/SRT. Após a mistura apropriada em uma extrusora de dupla rosca co-rotante e a moldagem por injeção, as propriedades mecânicas (resistência à tração e a resistência ao impacto foram determinadas e usadas como variáveis de resposta. A microscopia eletrônica de varredura (MEV foi usada para investigar a morfologia das diferentes misturas e interpretar os resultados. Com ferramentas estatísticas específicas, um número mínimo de experimentos permitiu o desenvolvimento de um modelo de superfície de resposta e a otimização das concentrações dos componentes de acordo com o desempenho mecânico. Valores elevados de resistência ao impacto são alcançados (>80 J.m-1 quando, de acordo com as condições experimentais estudadas, a mistura física de PP/EPDM/SRT mantém as proporções de EPDM e SRT em torno de 25%.The response surface methodology (RSM is a collection of statistical and mathematical techniques for developing, improving and optimizing processes. In this study, RSM technique was applied to the investigation of the mechanical behavior of different PP/EPDM/SRT ternary mixtures. After appropriate processing in a co-rotating twin extruder and injection molding, the mechanical properties, such as tensile strength and impact strength, were determined and used as response variables. Scanning electron microscopy (SEM was used for investigating the morphology of the different blends and to interpret the results. With specific statistical tools, a minimum number of experiments allowed the response surface model to be developed and the concentrations of the components to be optimized according to the mechanical performance. High values of impact

  8. Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

    Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David [Dept.of Veteran Affairs, New York Harbor Healthcare System, Brooklyn (United States); Rineer, Justin [University of Florida Health Cancer Center, Orlando (United States)


    To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

  9. Visualization of endothelial actin cytoskeleton in the mouse retina.

    Alessia Fraccaroli

    Full Text Available Angiogenesis requires coordinated changes in cell shape of endothelial cells (ECs, orchestrated by the actin cytoskeleton. The mechanisms that regulate this rearrangement in vivo are poorly understood - largely because of the difficulty to visualize filamentous actin (F-actin structures with sufficient resolution. Here, we use transgenic mice expressing Lifeact-EGFP to visualize F-actin in ECs. We show that in the retina, Lifeact-EGFP expression is largely restricted to ECs allowing detailed visualization of F-actin in ECs in situ. Lifeact-EGFP labels actin associated with cell-cell junctions, apical and basal membranes and highlights actin-based structures such as filopodia and stress fiber-like cytoplasmic bundles. We also show that in the skin and the skeletal muscle, Lifeact-EGFP is highly expressed in vascular mural cells (vMCs, enabling vMC imaging. In summary, our results indicate that the Lifeact-EGFP transgenic mouse in combination with the postnatal retinal angiogenic model constitutes an excellent system for vascular cell biology research. Our approach is ideally suited to address structural and mechanistic details of angiogenic processes, such as endothelial tip cell migration and fusion, EC polarization or lumen formation.

  10. Ischemic tolerance protects the rat retina from glaucomatous damage.

    Nicolás Belforte

    Full Text Available Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i intraocular pressure (IOP, ii retinal function (electroretinogram (ERG, iii visual pathway function (visual evoked potentials, (VEPs iv histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.

  11. The Analysis of Artificial Retina Organization for Signal Processing



    Machine vision is an active branch of artificial intelligence. An important problem in this area is the trade-off among efficiency, accuracy and computation complexity. The human visual system can keep watchfulness to the perimeter of a viewing field while at the same time focus on the center of the field for fine information processing. This mechanism of appropriate assignment of computing resources can reduce the demand for huge and complex hardware structure. Therefore, the design of a computer model based on the biological visual mechanism is an effective approach to resolve problems in machine vision. In this paper, a multi-layer neural model is developed based on the features of receptive field of ganglion in retina to simulate multi-scale perceptive fields of ganglion cell. The neural model can maintain alert on the outer area of the image while capturing and processing more important information in the central part. It may provide valuable inspiration for the implementation of real-time processing and avoidance of huge computation in machine vision.

  12. Islet-1 Immunoreactivity in the Developing Retina of Xenopus laevis

    Guadalupe Álvarez-Hernán


    Full Text Available The LIM-homeodomain transcription factor Islet1 (Isl1 has been widely used as a marker of neuronal differentiation in the developing visual system of different classes of vertebrates, including mammals, birds, reptiles, and fish. In the present study, we analyzed the spatial and temporal distribution of Isl1-immunoreactive cells during Xenopus laevis retinal development and its relation to the formation of the retinal layers, and in combination with different markers of cell differentiation. The earliest Isl1 expression appeared at St29-30 in the cell nuclei of sparse differentiating neuroblasts located in the vitreal surface of the undifferentiated retina. At St35-36, abundant Isl1-positive cells accumulated at the vitreal surface of the neuroepithelium. As development proceeded and through the postmetamorphic juveniles, Isl1 expression was identified in subpopulations of ganglion cells and in subsets of amacrine, bipolar, and horizontal cells. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different retinal cell types, and Isl1 can serve as a specific molecular marker for the study of retinal cell specification in X. laevis.

  13. Stimulation of the retina with a multielectrode extraocular visual prosthesis.

    Chowdhury, Vivek; Morley, John W; Coroneo, Minas T


    An extraocular approach to developing a retinal prosthesis for blind patients using electrodes placed on the outer surface of the eye is suggested. Experiments were carried out to determine the feasibility of this approach, and evaluate electrode configurations and parameters for stimulation. In anaesthetized cats, a 21-electrode extraocular retinal prosthesis (ERP) array was sutured to the sclera over the lateral surface of the eye. Electrically evoked potentials (EEP) were recorded at the visual cortex bilaterally in response to retinal stimulation with the electrode array. Bipolar stimulation of the ERP array electrodes in horizontal and vertical configurations and at different interelectrode separations was investigated with biphasic constant-current pulses. Electrical stimulation of the lateral retina with an ERP elicited EEP that were higher in the ipsilateral visual cortex. The threshold for bipolar retinal stimulation was 500 microA. EEP amplitude increased with increases in stimulus pulse duration and current intensity. Retinal stimulation was slightly more effective with electrodes in a vertical as opposed to horizontal orientation. A larger interelectrode separation resulted in a higher EEP amplitude. Retinal stimulation with a prototype ERP array is demonstrated. The thresholds for retinal excitation are below safe charge-density limits for chronic neural stimulation. Ipsilateral localization of the EEP suggests that localized retinal stimulation is occurring. An ERP is a new approach to retinal prosthesis research, and might lead to the development of a low-resolution visual prosthesis for blind patients.

  14. Microcystic macular edema detection in retina OCT images

    Swingle, Emily K.; Lang, Andrew; Carass, Aaron; Ying, Howard S.; Calabresi, Peter A.; Prince, Jerry L.


    Optical coherence tomography (OCT) is a powerful imaging tool that is particularly useful for exploring retinal abnormalities in ophthalmological diseases. Recently, it has been used to track changes in the eye associated with neurological diseases such as multiple sclerosis (MS) where certain tissue layer thicknesses have been associated with disease progression. A small percentage of MS patients also exhibit what has been called microcystic macular edema (MME), where uid collections that are thought to be pseudocysts appear in the inner nuclear layer. Very little is known about the cause of this condition so it is important to be able to identify precisely where these pseudocysts occur within the retina. This identi cation would be an important rst step towards furthering our understanding. In this work, we present a detection algorithm to nd these pseudocysts and to report on their spatial distribution. Our approach uses a random forest classi er trained on manual segmentation data to classify each voxel as pseudocyst or not. Despite having a small sample size of ve subjects, the algorithm correctly identi es 84.6% of pseudocysts as compared to manual delineation. Finally, using our method, we show that the spatial distribution of pseudocysts within the macula are generally contained within an annulus around the fovea.

  15. Mapping a complete neural population in the retina.

    Marre, Olivier; Amodei, Dario; Deshmukh, Nikhil; Sadeghi, Kolia; Soo, Frederick; Holy, Timothy E; Berry, Michael J


    Recording simultaneously from essentially all of the relevant neurons in a local circuit is crucial to understand how they collectively represent information. Here we show that the combination of a large, dense multielectrode array and a novel, mostly automated spike-sorting algorithm allowed us to record simultaneously from a highly overlapping population of >200 ganglion cells in the salamander retina. By combining these methods with labeling and imaging, we showed that up to 95% of the ganglion cells over the area of the array were recorded. By measuring the coverage of visual space by the receptive fields of the recorded cells, we concluded that our technique captured a neural population that forms an essentially complete representation of a region of visual space. This completeness allowed us to determine the spatial layout of different cell types as well as identify a novel group of ganglion cells that responded reliably to a set of naturalistic and artificial stimuli but had no measurable receptive field. Thus, our method allows unprecedented access to the complete neural representation of visual information, a crucial step for the understanding of population coding in sensory systems.

  16. Cholesterol in the retina: the best is yet to come

    Pikuleva, Irina A.; Curcio, Christine A.


    Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

  17. Spare the rods and spoil the retina: revisited.

    Sivaprasad, S; Arden, G


    Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the high metabolic activity required to maintain the dark current. Therefore, Arden hypothesized that in diabetes where oxygen supply may also be affected due to the changes in retinal vasculature, prevention of dark adaptation may be a viable option to prevent or decrease the rate of progression of diabetic retinopathy. Animal experiments have proven that the absence of rods decreases the development of retinal neovascularisation. The same principle applies to panretinal photocoagulation, an established treatment for proliferative diabetic retinopathy. Recently, a few clinical studies have also shown that preventing dark adaptation by suppressing rods with 500-nm light source at night decreases the rate of progression of early diabetic retinopathy and maculopathy in the short-term. We await the results of a large two-year multi-centre trial (CLEOPATRA trial) to evaluate the long-term effects of decreasing dark adaptation by applying a 500nm light source as a mask over eyes with non-central diabetic macular oedema.

  18. Comparison of Diode and Argon Laser Lesions in Rabbit Retina

    Hui Zhang; Xiaoxin Li; Bin Li; Jiping Da


    Purpose: To compare the histological alteration of retina with various spot intensities between diode and argon lasers in order to instruct the clinical use of 810 nm diode laser.Methods: Transpupillary retinal photocoagulations were performed on 42 eyes of 27pigmented rabbits. Histopathologic alteration of lesions in different intensities and different time intervals after irradiation produced by diode and argon laser was observed and compared using light microscopy. Areas of various lesions measured by image analysis system (CMIAS) were compared quantitatively.Results: Histopathologically, two-week-old grade 2 lesions produced by diode laser induced the disappearance of outer nuclear cells. More than a half of all showed reduction in number of outer nuclear layer cells in argon. Fibroblasts appeared in the diode grade 3lesions 5 days after irradiation. CMIAS data showed that all the areas of diode lesions immediately after photocoagulation were to be larger than those of argon laser lesions in the same spot intensity (P < 0.05). However, twenty-four hours after photocoagulation, the area of the diode lesions increased less than that of the argon laser lesions (8%vs.23%).Conclusion: The acute histological effect caused by 810 nm diode laser and argon green laser is similar,while the expansion of lesion area 24 hours after photocoagulation was less with the diode laser compared to the argon. This may be the first report in the literature regarding quantitative analysis of the delayed reaction of argon green lasers.

  19. Feedback synaptic interaction in the dragonfly ocellar retina


    The intracellular response of the ocellar nerve dendrite, the second order neuron in the retina of the dragonfly ocellus, has been modified by application of various drugs and a model developed to explain certain features of that response. Curare blocked the response completely. Both picrotoxin and bicuculline eliminated the "off" overshoot. Bicuculline also decreased the size of response and the sensitivity. gamma-Aminobutyric acid (GABA), however, increased the size of response. The evidence indicates the possibility that the receptor transmitter is acetylcholine and is inhibitory to the ocellar nerve dendrite whereas the feedback transmitter from the ocellar nerve dendrite may be GABA and is facilitory to receptor transmitter release. The model of synaptic feedback interaction developed to be consistent with these results has certain important features. It suggests that the feedback transmitter is released in the dark to increase input sensitivity from receptors in response to dim light. This implies that the dark potential of the ocellar nerve dendrite may be determined by a dynamic equilibrium established by synaptic interaction between it and the receptor terminals. Such a system is also well suited to signalling phasic information about changes in level of illumination over a wide range of intensities, a characteristic which appears to be a significant feature of the dragonfly median ocellar response. PMID:205624

  20. Mouse embryonic retina delivers information controlling cortical neurogenesis.

    Ciro Bonetti

    Full Text Available The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal. Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.

  1. Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators.

    Weitz, Andrew C; Behrend, Matthew R; Lee, Nan Sook; Klein, Ronald L; Chiodo, Vince A; Hauswirth, William W; Humayun, Mark S; Weiland, James D; Chow, Robert H


    Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.

  2. The ciliary margin zone of the mammalian retina generates retinal ganglion cells

    Marcucci, Florencia; Murcia-Belmonte, Veronica; Coca, Yaiza; Ferreiro-Galve, Susana; Wang, Qing; Kuwajima, Takaaki; Khalid, Sania; Ross, M. Elizabeth; Herrera, Eloisa; Mason, Carol


    Summary The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity. PMID:28009286

  3. Hazardous effects of fried potato chips on the development of retina in albino rats

    Hassan I El-Sayyad; Saber A Sakr; Gamal M Badawy; Hanaa S Afify


    Objective: To evaluate the hazardous effects of fried potato chips upon the retina of two developmental stages of the albino rats aged 7 and 14 days from parturition. Methods: Pregnant rats were arranged into two groups: control pregnant rats and consequently their delivered newborns until reaching 7 and 14 days old from parturition and fried potato chips group in which pregnant rats at the 6th day of gestation maintained on diet formed of fried potato chips supplied from the market mixed with standard diet at a concentration of 50% per each till 7 and 14 post-partum. Three fold integrated approaches were adopted, namely, histological, ultrastructural and proteomic analysis. Results: Histological examination of the retina of the experimental offsprings revealed many histopathological changes, including massive degeneration, vacuolization and cell loss in the ganglion cell layer, as well as general reduction in retinal size. At the ultrastructural level, the retina of experimental offsprings exhibited number of deformities, including ill differentiated and degenerated nuclear layer, malformed and vacuolated pigment epithelium with vesiculated and fragmented rough endoplasmic reticulum, degenerated outer segment of photoreceptors, as well as swollen choriocapillaris and loss of neuronal cells. Proteomic analysis of retina of the two experimental developmental stages showed variations in the expressed proteins as a result of intoxication which illustrated the adverse toxic effects of fried potato chips upon the retina. Conclusions: It can be concluded that the effect of fried potato chips on the development of retina in rats may be due to the presence of acrylamide or its metabolite.

  4. Streaming an image through the eye: The retina seen as a dithered scalable image coder

    Masmoudi, Khaled; Kornprobst, Pierre


    We propose the design of an original scalable image coder/decoder that is inspired from the mammalians retina. Our coder accounts for the time-dependent and also nondeterministic behavior of the actual retina. The present work brings two main contributions: As a first step, (i) we design a deterministic image coder mimicking most of the retinal processing stages and then (ii) we introduce a retinal noise in the coding process, that we model here as a dither signal, to gain interesting perceptual features. Regarding our first contribution, our main source of inspiration will be the biologically plausible model of the retina called Virtual Retina. The main novelty of this coder is to show that the time-dependent behavior of the retina cells could ensure, in an implicit way, scalability and bit allocation. Regarding our second contribution, we reconsider the inner layers of the retina. We emit a possible interpretation for the non-determinism observed by neurophysiologists in their output. For this sake, we mode...

  5. Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina

    Rachel, Rivka A.; Dolen, Gul; Hayes, Nancy L.; Lu, Alice; Erskine, Lynda; Nowakowski, Richard S.; Mason, Carol A.


    In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

  6. [Ultrastructure of melanocytes from retina and choroid of the Pacific salmon].

    Zagal'skaia, E O


    The ultrastructure of the retina and choroid cells in three species of the Pacific salmon, Oncohrynchus gorbuscha, O. keta and O. masou, was studied. The structure of retina pigment cells is similar in all the three species, only a small difference was found in the percentage of lengthened and rounded forms of melanosomes. Melanocytes of the masu salmon differ also in the structure of their nuclei. The pigment cells of choroid differ from those of retina by a more extended form of melanosomes and by the presence of less rounded melanosomes. In the chum salmon retina we found electron lucent "contact vesicles", whose assignment is open to discussion. In retina pigment cells of the masu salmon smolts ready for migration, the activity of Golgi appararus rises, mitochondria and mature melanosomes increase in number. The choroid pigment cells are slightly swollen, their processes more often and deeper penetrate into the walls of vessels, down to the endothelium. Results of the experiment with the application of an artificial magnetic field (AMF) have shown that the retina and choroid pigment cells in the masu salmon fry react to the field of a certain direction. The phenomenon of magnetosensitivity of pigment cells is discussed in addition to their possible involvement in magnetoreception.

  7. Defects in the outer limiting membrane are associated with rosette development in the Nrl-/- retina.

    Michael W Stuck

    Full Text Available The neural retinal leucine zipper (Nrl knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl(-/- retina, rods are converted into functional cone-like cells. The Nrl(-/- retina is characterized by large undulations of the outer nuclear layer (ONL commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl(-/- retina. We report that rosettes first appear at postnatal day (P8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and Müller glia which comprise the retinal outer limiting membrane (OLM are not uniformly formed in the Nrl(-/- retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl(-/- retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM.

  8. Defects in the outer limiting membrane are associated with rosette development in the Nrl-/- retina.

    Stuck, Michael W; Conley, Shannon M; Naash, Muna I


    The neural retinal leucine zipper (Nrl) knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl(-/-) retina, rods are converted into functional cone-like cells. The Nrl(-/-) retina is characterized by large undulations of the outer nuclear layer (ONL) commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl(-/-) retina. We report that rosettes first appear at postnatal day (P)8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and Müller glia which comprise the retinal outer limiting membrane (OLM) are not uniformly formed in the Nrl(-/-) retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl(-/-) retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM.

  9. Cholesterol in mouse retina originates primarily from in situ de novo biosynthesis.

    Lin, Joseph B; Mast, Natalia; Bederman, Ilya R; Li, Yong; Brunengraber, Henri; Björkhem, Ingemar; Pikuleva, Irina A


    The retina, a thin tissue in the back of the eye, has two apparent sources of cholesterol: in situ biosynthesis and cholesterol available from the systemic circulation. The quantitative contributions of these two cholesterol sources to the retinal cholesterol pool are unknown and have been determined in the present work. A new methodology was used. Mice were given separately deuterium-labeled drinking water and chow containing 0.3% deuterium-labeled cholesterol. In the retina, the rate of total cholesterol input was 21 μg of cholesterol/g retina • day, of which 15 μg of cholesterol/g retina • day was provided by local biosynthesis and 6 μg of cholesterol/g retina • day was uptaken from the systemic circulation. Thus, local cholesterol biosynthesis accounts for the majority (72%) of retinal cholesterol input. We also quantified cholesterol input to mouse brain, the organ sharing important similarities with the retina. The rate of total cerebral cholesterol input was 121 μg of cholesterol/g brain • day with local biosynthesis providing 97% of total cholesterol input. Our work addresses a long-standing question in eye research and adds new knowledge to the potential use of statins (drugs that inhibit cholesterol biosynthesis) as therapeutics for age-related macular degeneration, a common blinding disease.

  10. A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys.

    Bouskila, Joseph; Javadi, Pasha; Elkrief, Laurent; Casanova, Christian; Bouchard, Jean-François; Ptito, Maurice


    The endocannabinoid (eCB) system is widely expressed in various parts of the central nervous system, including the retina. The localization of the key eCB receptors, particularly CB1R and CB2R, has been recently reported in rodent and primate retinas with striking interspecies differences. Little is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system in the retina of mice, tree shrews, and monkeys. We found that CB1R and FAAH distributions are well-preserved among these species. However, expression of NAPE-PLD is circumscribed to the photoreceptor layer only in monkeys. In contrast, CB2R expression is variable across these species; in mice, CB2R is found in retinal neurons but not in glial cells; in tree shrews, CB2R is expressed in Müller cell processes of the outer retina and in retinal neurons of the inner retina; in monkeys, CB2R is restricted to Müller cells. Finally, the expression patterns of MAGL and DAGLα are differently expressed across species. Overall, these results provide evidence that the eCB system is differently expressed in the retina of these mammals and suggest a distinctive role of eCBs in visual processing.

  11. A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys

    Joseph Bouskila


    Full Text Available The endocannabinoid (eCB system is widely expressed in various parts of the central nervous system, including the retina. The localization of the key eCB receptors, particularly CB1R and CB2R, has been recently reported in rodent and primate retinas with striking interspecies differences. Little is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system in the retina of mice, tree shrews, and monkeys. We found that CB1R and FAAH distributions are well-preserved among these species. However, expression of NAPE-PLD is circumscribed to the photoreceptor layer only in monkeys. In contrast, CB2R expression is variable across these species; in mice, CB2R is found in retinal neurons but not in glial cells; in tree shrews, CB2R is expressed in Müller cell processes of the outer retina and in retinal neurons of the inner retina; in monkeys, CB2R is restricted to Müller cells. Finally, the expression patterns of MAGL and DAGLα are differently expressed across species. Overall, these results provide evidence that the eCB system is differently expressed in the retina of these mammals and suggest a distinctive role of eCBs in visual processing.

  12. Viral vectors for targeting the canine retina: a review.

    Petersen-Jones, Simon M


    Clinical trials are currently underway using gene therapy to treat retinal disease such as Leber congenital amaurosis (LCA). Viral vectors that have been utilized to target retinal cells include adenoviruses, lentiviruses, and recombinant adeno-associated viruses (rAAV). Of the three classes, rAAV vectors show the greatest promise for retinal gene therapy. Recent developments in virus technology such as the development of hybrid and capsid mutant rAAV vectors mean that specific retinal cells can be targeted and faster stronger transgene expression is now possible compared to that achieved with the first generation of vectors. Gene therapy trials in dogs have been very important in the development of therapy for RPE65 LCA which is currently in phase I/II clinical trials in humans. Recent successes in using gene therapy to treat canine achromatopsia, X-linked progressive retinal atrophy (PRA) and the more severe rapid degenerations such as rod-cone dysplasia type 3 may lead also to the translation to human clinical trials. Dogs have played and continue to play an important role as animal models for proof-of-concept studies of retinal gene therapy. As modifications and improvements in gene therapy protocols are made from experience gathered from human clinical trials perhaps gene therapy for the treatment of canine clinical patients will become available to veterinary ophthalmologists. © 2012 American College of Veterinary Ophthalmologists.

  13. Human dental pulp stem cells respond to cues from the rat retina and differentiate to express the retinal neuronal marker rhodopsin.

    Bray, A F; Cevallos, R R; Gazarian, K; Lamas, M


    Human adult dental pulp stem cells (DPSCs) are self-renewing stem cells that originate from the neural crest during development and remain within the dental pulp niche through adulthood. Due to their multi-lineage differentiation potential and their relative ease of access they represent an exciting alternative for autologous stem cell-based therapies in neurodegenerative diseases. In animal models, DPSCs transplanted into the brain differentiate into functional neurons or astrocytes in response to local environmental cues that appear to influence the fate of the surviving cells. Here we tested the hypothesis that DPSCs might be able to respond to factors present in the retina enabling the regenerative potential of these cells. We evaluated the response of DPSCs to conditioned media from organotypic explants from control and chemically damaged rat retinas. To evaluate cell differentiation, we analyzed the expression of glial fibrillary acidic protein (GFAP), early neuronal and retinal markers (polysialic acid-neural cell adhesion molecule (PSA-NCAM); Pax6; Ascl1; NeuroD1) and the late photoreceptor marker rhodopsin, by immunofluorescence and reverse transcription polymerase chain reaction (RT-PCR). Exposure of DPSC cultures to conditioned media from control retinas induced a 39% reduction on the number of DPSCs that expressed GFAP; the expression of Pax6, Ascl1, PSA-NCAM or NeuroD1 was undetectable or did not change significantly. Expression of rhodopsin was not detectable in control or after exposure of the cultures with retinal conditioned media. By contrast, 44% of DPSCs exposed to conditioned media from damaged retinas were immunopositive to this protein. This response could not be reproduced when conditioned media from Müller-enriched primary cultures was used. Finally, quantitative RT-PCR was performed to compare the relative expression of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and brain

  14. Expression and cellular localization of the Mas receptor in the adult and developing mouse retina.

    Prasad, Tuhina; Verma, Amrisha; Li, Qiuhong


    Recent studies have provided evidence that a local renin-angiotensin system (RAS) exists in the retina and plays an important role in retinal neurovascular function. We have recently shown that increased expression of ACE2 and angiotensin (1-7) [Ang (1-7)], two components of the protective axis of the RAS, in the retina via adeno-associated virus (AAV)-mediated gene delivery, conferred protection against diabetes-induced retinopathy. We hypothesized that the protective molecular and cellular mechanisms of Ang (1-7) are mediated by its receptor, Mas, and the expression level and cellular localization dictate the response to Ang (1-7) and activation of subsequent protective signaling pathways. We tested this hypothesis by examining the expression and cellular localization of the Mas receptor in adult and developing mouse retinas. The cellular localization of the Mas receptor protein was determined with immunofluorescence of the eyes of adult and postnatal day 1 (P1), P5, P7, P15, and P21 mice using the Mas receptor-specific antibody, and mRNA was detected with in situ hybridization of paraffin-embedded sections. Western blotting and real-time reverse-transcription (RT)-PCR analysis were performed to determine the relative levels of the Mas protein and mRNA in adult and developing retinas, as well as in cultured retinal Müller glial and RPE cells. In the adult eye, the Mas receptor protein was abundantly present in retinal ganglion cells (RGCs) and photoreceptor cells; a lower level of expression was observed in endothelial cells, Müller glial cells, and other neurons in the inner nuclear layer of the retina. In the developing retina, Mas receptor mRNA and protein expression was detected in the inner retina at P1, and the expression levels increased with age to reach the adult level and pattern by P15. In the adult mouse retina, Mas receptor mRNA was expressed at a much higher level when compared to angiotensin II (Ang II) type I (AT1R) and type II (AT2R) receptor m

  15. BMP-induced reprogramming of the neural retina into retinal pigment epithelium requires Wnt signalling

    Jörg Steinfeld


    Full Text Available In vertebrates, the retinal pigment epithelium (RPE and photoreceptors of the neural retina (NR comprise a functional unit required for vision. During vertebrate eye development, a conversion of the RPE into NR can be induced by growth factors in vivo at optic cup stages, but the reverse process, the conversion of NR tissue into RPE, has not been reported. Here, we show that bone morphogenetic protein (BMP signalling can reprogram the NR into RPE at optic cup stages in chick. Shortly after BMP application, expression of Microphthalmia-associated transcription factor (Mitf is induced in the NR and selective cell death on the basal side of the NR induces an RPE-like morphology. The newly induced RPE differentiates and expresses Melanosomalmatrix protein 115 (Mmp115 and RPE65. BMP-induced Wnt2b expression is observed in regions of the NR that become pigmented. Loss of function studies show that conversion of the NR into RPE requires both BMP and Wnt signalling. Simultaneous to the appearance of ectopic RPE tissue, BMP application reprogrammed the proximal RPE into multi-layered retinal tissue. The newly induced NR expresses visual segment homeobox-containing gene (Vsx2, and the ganglion and photoreceptor cell markers Brn3α and Visinin are detected. Our results show that high BMP concentrations are required to induce the conversion of NR into RPE, while low BMP concentrations can still induce transdifferentiation of the RPE into NR. This knowledge may contribute to the development of efficient standardized protocols for RPE and NR generation for cell replacement therapies.

  16. Lycium barbarum (wolfberry reduces secondary degeneration and oxidative stress, and inhibits JNK pathway in retina after partial optic nerve transection.

    Hongying Li

    Full Text Available Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP are neuroprotective for retinal ganglion cells (RGCs in different animal models. Protecting RGCs from secondary degeneration is a promising direction for therapy in glaucoma management. The complete optic nerve transection (CONT model can be used to study primary degeneration of RGCs, while the partial optic nerve transection (PONT model can be used to study secondary degeneration of RGCs because primary degeneration of RGCs and secondary degeneration can be separated in location in the same retina in this model; in other situations, these types of degeneration can be difficult to distinguish. In order to examine which kind of degeneration LBP could delay, both CONT and PONT models were used in this study. Rats were fed with LBP or vehicle daily from 7 days before surgery until sacrifice at different time-points and the surviving numbers of RGCs were evaluated. The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK pathways were detected with Western-blot analysis. LBP did not delay primary degeneration of RGCs after either CONT or PONT, but it did delay secondary degeneration of RGCs after PONT. We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1. This study suggests that LBP can delay secondary degeneration of RGCs and this effect may be linked to inhibition of oxidative stress and the JNK/c-jun pathway in the retina.

  17. Stem cell therapy for retinal diseases

    Jose Mauricio Garcia,; Luisa Mendon?a; Rodrigo Brant; Murilo Abud; Caio Regatieri; Bruno Diniz


    In this review, we discuss about current knowledgeabout stem cell (SC) therapy in the treatment of retinaldegeneration. Both human embryonic stem cell andinduced pluripotent stem cell has been growth inculture for a long time, and started to be explored inthe treatment of blinding conditions. The Food andDrug Administration, recently, has granted clinical trialsusing SC retinal therapy to treat complex disorders, asStargardt's dystrophy, and patients with geographicatrophy, providing good outcomes. This study'sintent is to overview the critical regeneration of thesubretinal anatomy through retinal pigment epitheliumtransplantation, with the goal of reestablish importantpathways from the retina to the occipital cortex of thebrain, as well as the differentiation from pluripotentquiescent SC to adult retina, and its relationshipwith a primary retinal injury, different techniques oftransplantation, management of immune rejection andtumorigenicity, its potential application in improvingpatients' vision, and, finally, approaching future directionsand challenges for the treatment of several conditions.

  18. [Radiation preconditioning of mouse retina results in tolerance to MNU-induced degeneration and stimulates retinal recovery].

    Tronov, V A; Vinogradova, Yu V; Poplinskaya, V A; Nekrasova, E I; Ostrovsky, M A


    Emerging body of data indicate protecting effect of low level of stress (preconditioning) on retina. Our previous studies have revealed a non-linear dose-response relationship for cytotoxic effect of both ionizing radiation and N-methyl-N-nitrosourea (MNU) on mouse retina. Moreover, non-cytotoxic dose of MNU increased tolerance of retina to following challenge dose of MNU. This result displays protection of retina through mechanism of recovery. In the present study we used the mouse model for MNU-induced retinal degeneration to evaluate the adaptive response of the retina to proton irradiation and implication of glial Muller cells in this response. In this paper, we have shown that the recovery of the retina after exposure to genotoxic agents is associated with an increased efficiency of DNA damage repair and lowered death of retinal photoreceptors.

  19. Generating 3D anatomically detailed models of the retina from OCT data sets: implications for computational modelling

    Shalbaf, Farzaneh; Dokos, Socrates; Lovell, Nigel H.; Turuwhenua, Jason; Vaghefi, Ehsan


    Retinal prosthesis has been proposed to restore vision for those suffering from the retinal pathologies that mainly affect the photoreceptors layer but keep the inner retina intact. Prior to costly risky experimental studies computational modelling of the retina will help to optimize the device parameters and enhance the outcomes. Here, we developed an anatomically detailed computational model of the retina based on OCT data sets. The consecutive OCT images of individual were subsequently segmented to provide a 3D representation of retina in the form of finite elements. Thereafter, the electrical properties of the retina were modelled by implementing partial differential equation on the 3D mesh. Different electrode configurations, that is bipolar and hexapolar configurations, were implemented and the results were compared with the previous computational and experimental studies. Furthermore, the possible effects of the curvature of retinal layers on the current steering through the retina were proposed and linked to the clinical observations.

  20. Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice.

    Cui, Xuezhi; Navneet, Soumya; Wang, Jing; Roon, Penny; Chen, Wei; Xian, Ming; Smith, Sylvia B


    Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. Retinas isolated from wild-type (WT), Mthfr+/-, and Cbs+/- mice (12 and 22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), cystathionine-β-synthase (CBS), and cystathionase (CTH) RNA/protein levels. Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 (xCT), taurine, taurine transporter (TAUT), and H2S. Aside from decreased CBS RNA/protein levels in Cbs+/- retinas, there were minimal alterations in remethylation/transsulfuration pathways in the two mutant mice strains. Glutathione and taurine levels in Mthfr+/- and Cbs+/- retinas were similar to WT, which may be due to robust levels of xCT and TAUT in mutant retinas. Interestingly, levels of H2S were markedly increased in retinas of Mthfr+/- and Cbs+/- mice compared with WT. Ganglion cell loss and vasculopathy observed in Mthfr+/- and Cbs+/- mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation of H2S is particularly intriguing owing to neuroprotective properties reported for this gasotransmitter.

  1. Adult peripheral blood mononuclear cells transdifferentiate in vitro and integrate into the retina in vivo.

    Liu, Qian; Guan, Liping; Huang, Bing; Li, Weihua; Su, Qiao; Yu, Minbin; Xu, Xiaoping; Luo, Ting; Lin, Shaochun; Sun, Xuerong; Chen, Mengfei; Chen, Xigu


    Adult peripheral blood-derived cells are able to differentiate into a variety of cell types, including nerve cells, liver-like cells and epithelial cells. However, their differentiation into retina-like cells is controversial. In the present study, transdifferentiation potential of human adult peripheral blood mononuclear cells into retina-like cells and integration into the retina of mice were investigated. Freshly isolated adult peripheral blood mononuclear cells were divided into two groups: cells in group I were cultured in neural stem cell medium, and cells in group II were exposed to conditioned medium from rat retinal tissue culture. After 5 days, several distinct cell morphologies were observed, including standard mononuclear, neurons with one or two axons and elongated glial-like cells. Immunohistochemical analysis of neural stem cell, neuron and retina cell markers demonstrated that cells in both groups were nestin-, MAP2 (microtubule-associated protein)- and GFAP (glial fibrillary acidic protein)-positive. Flow cytometry results suggested a significant increase in nestin-, MAP2- and CD16-positive cells in group I and nestin-, GFAP-, MAP2-, vimentin- and rhodopsin-positive cells in group II. To determine survival, migration and integration in vivo, cell suspensions (containing group I or group II cells) were injected into the vitreous or the peritoneum. Tissue specimens were obtained and immunostained 4 weeks after transplantation. We found that cells delivered by intravitreal injection integrated into the retina. Labelled cells were not detected in the retina of mice receiving differentiated cells by intraperitoneal injection, but cells (groups I and II) were detected in the liver and spleen. Our findings revealed that human adult peripheral blood mononuclear cells could be induced to transdifferentiate into neural precursor cells and retinal progenitor cells in vitro, and the differentiated peripheral blood mononuclear cells can migrate and integrate

  2. Cold Shock Proteins Are Expressed in the Retina Following Exposure to Low Temperatures

    Contartese, Daniela S.; Rolón, Federico; Sarotto, Anibal; Dorfman, Veronica B.; Loidl, Cesar F.; Martínez, Alfredo


    Hypothermia has been proposed as a therapeutic intervention for some retinal conditions, including ischemic insults. Cold exposure elevates expression of cold-shock proteins (CSP), including RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding protein (CIRP), but their presence in mammalian retina is so far unknown. Here we show the effects of hypothermia on the expression of these CSPs in retina-derived cell lines and in the retina of newborn and adult rats. Two cell lines of retinal origin, R28 and mRPE, were exposed to 32°C for different time periods and CSP expression was measured by qRT-PCR and Western blotting. Neonatal and adult Sprague-Dawley rats were exposed to a cold environment (8°C) and expression of CSPs in their retinas was studied by Western blotting, multiple inmunofluorescence, and confocal microscopy. RBM3 expression was upregulated by cold in both R28 and mRPE cells in a time-dependent fashion. On the other hand, CIRP was upregulated in R28 cells but not in mRPE. In vivo, expression of CSPs was negligible in the retina of newborn and adult rats kept at room temperature (24°C). Exposure to a cold environment elicited a strong expression of both proteins, especially in retinal pigment epithelium cells, photoreceptors, bipolar, amacrine and horizontal cells, Müller cells, and ganglion cells. In conclusion, CSP expression rapidly rises in the mammalian retina following exposure to hypothermia in a cell type-specific pattern. This observation may be at the basis of the molecular mechanism by which hypothermia exerts its therapeutic effects in the retina. PMID:27556928

  3. Optical imaging of the retina in response to the electrical stimulation

    Fujikado, Takashi; Okawa, Yoshitaka; Miyoshi, Tomomitsu; Hirohara, Yoko; Mihashi, Toshifumi; Tano, Yasuo


    Purposes: To determine if reflectance changes of the retina can be detected following electrical stimulation to the retina using a newly developed optical-imaging fundus camera. Methods: Eyes of cats were examined after pupil dilation. Retina was stimulated either focally by a ball-type electrode (BE) placed on the fenestrated sclera or diffusely using a ring-type electrode (RE) placed on the corneoscleral limbus. Electrical stimulation by biphasic pulse trains was applied for 4 seconds. Fundus images with near-infrared (800-880 nm) light were obtained between 2 seconds before and 20 seconds after the electrical stimulation (ES). A two-dimensional map of the reflectance changes (RCs) was constructed. The effect of Tetrodotoxin (TTX) was also investigated on RCs by ES using RE. Results: RCs were observed around the retinal locus where the stimulating electrodes were positioned (BE) or in the retina of the posterior pole (RE), in which the latency was about 0.5 to 1.0 sec and the peak time about 2 to 5 sec after the onset of ES. The intensity of the RCs increased with the increase of the stimulus current in both cases. RCs were completely suppressed after the injection of TTX. Conclusions: The functional changes of the retina either by focal or diffuse electrical stimulation were successfully detected by optical imaging of the retina. The contribution of retinal ganglion cells on RCs by ES was confirmed by TTX experiment. This method may be applied to the objective evaluation of the artificial retina.

  4. Circadian modulation of crustacean hyperglycemic hormone in crayfish eyestalk and retina.

    Fanjul-Moles, Maria Luisa; Escamilla-Chimal, Elsa Guadalupe; Salceda, Rocio; Giulianini, Piero G; Sánchez-Chávez, Gustavo


    Previous studies suggested the retina could be a putative locus of daily crustacean hyperglycemic hormone (CHH) secretion, as it possesses its own metabolic machinery and is independent of the well-known CHH eyestalk locus responsible for the circadian secretion of this peptide. However, it has been proposed that hemolymph glucose and lactate concentrations play a dual role in the regulation of CHH in crayfish. To elucidate the temporal relationship between these two different CHH production loci and to examine their relationship with glucose regulation, we investigated the expression of CHH daily and circadian rhythms in the eyestalk and retina of crayfish using biochemical methods and time series analysis. We wanted to determine whether (1) putative retina and eyestalk CHH rhythmic expressions are correlated and if the oscillations of the two metabolic products of lactate and glucose in the blood due to CHH action on the target tissue correlate, and (2) retina CHH (RCHH) and the possible retinal substrate glycogen and its product glucose are temporally correlated. We found a negative correlation between daily and circadian changes of relative CHH abundance in the retina and eyestalk. This correlation and the cross-correlation values found between eyestalk CHH and hemolymph and glucose confirm that CHH produced by the X-organ sinus gland complex is under the previously proposed dual feedback control system over the 24 h time period. However, the presence of both glycogen and glucose in the retina, the cross-correlation values found between these parameters and hemolymph lactate and glucose, as well as RCHH and hemolymph and retina metabolic markers suggest RCHH is not under the same temporal metabolic control as eyestalk CHH. Nonetheless, their expression may be linked to common rhythms-generating processes.

  5. Neural retina identity is specified by lens-derived BMP signals.

    Pandit, Tanushree; Jidigam, Vijay K; Patthey, Cedric; Gunhaga, Lena


    The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.

  6. [Finite element analysis of temperature field of retina by electrical stimulation with microelectrode array].

    Wang, Wei; Qiao, Qingli; Gao, Weiping; Wu, Jun


    We studied the influence of electrode array parameters on temperature distribution to the retina during the use of retinal prosthesis in order to avoid thermal damage to retina caused by long-term electrical stimulation. Based on real epiretinal prosthesis, a three-dimensional model of electrical stimulation for retina with 4 X 4 microelectrode array had been established using the finite element software (COMSOL Multiphysics). The steady-state temperature field of electrical stimulation of the retina was calculated, and the effects of the electrode parameters such as the distance between the electrode contacts, the materials and area of the electrode contact on temperature field were considered. The maximum increase in the retina steady temperature was about 0. 004 degrees C with practical stimulation current. When the distance between the electrode contacts was changed from 130 microm to 520 microm, the temperature was reduced by about 0.006 microC. When the contact radius was doubled from 130 microm to 260 microm, the temperature decrease was about 0.005 degrees C. It was shown that there were little temperature changes in the retina with a 4 x 4 epiretinal microelectrode array, reflecting the safety of electrical stimulation. It was also shown that the maximum temperature in the retina decreased with increasing the distance between the electrode contacts, as well as increasing the area of electrode contact. However, the change of the maximum temperature was very small when the distance became larger than the diameter of electrode contact. There was no significant difference in the effects of temperature increase among the different electrode materials. Rational selection of the distance between the electrode contacts and their area in electrode design can reduce the temperature rise induced by electrical stimulation.

  7. Immunolocalization of the P2X4 receptor on neurons and glia in the mammalian retina.

    Ho, T; Vessey, K A; Fletcher, E L


    Extracellular adenosine 5'-triphosphate (eATP) acts as a neurotransmitter within the retina and brain, activating a range of ionotropic P2X and metabotropic P2Y receptors. In this study, the specific localization of the P2X4 receptor (P2X4-R) subunit was evaluated in the retina using fluorescence immunohistochemistry and pre-embedding immuno-electron microscopy. Punctate P2X4-R labeling was largely localized to the inner and outer plexiform layers of mouse, rat and cat retinae. In the mouse outer retina, double-labeling of P2X4-R with the horizontal cell marker, calbindin, revealed P2X4-R immunoreactivity (P2X4-R-IR) on horizontal cell somata and processes. In the inner retina, P2X4-R expression was found closely associated with rod and cone bipolar cell terminals, and the punctate labeling was observed on calretinin-positive amacrine cells. Using immuno-electron microscopy, P2X4-Rs were observed on processes post-synaptic to photoreceptor and bipolar cell terminals, likely representing horizontal, amacrine and ganglion cells, respectively. Furthermore, P2X4-R expression was also observed on Müller cells, astrocytes and microglia. These data suggest a role for P2X4-Rs in the lateral inhibitory pathways of the retina, modulating neuronal function of photoreceptors and bipolar cells. The expression on macro- and microglial cells implicates a role for P2X4-Rs in glial signaling, tissue homeostasis and immunosurveillance within the mammalian retina.

  8. Expression of inducible nitric oxide synthase (iNOS) in microglia of the developing quail retina.

    Sierra, Ana; Navascués, Julio; Cuadros, Miguel A; Calvente, Ruth; Martín-Oliva, David; Ferrer-Martín, Rosa M; Martín-Estebané, María; Carrasco, María-Carmen; Marín-Teva, José L


    Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid

  9. Mechanical spectroscopy of retina explants at the protein level employing nanostructured scaffolds.

    Mayazur Rahman, S; Reichenbach, Andreas; Zink, Mareike; Mayr, Stefan G


    Development of neuronal tissue, such as folding of the brain, and formation of the fovea centralis in the human retina are intimately connected with the mechanical properties of the underlying cells and the extracellular matrix. In particular for neuronal tissue as complex as the vertebrate retina, mechanical properties are still a matter of debate due to their relation to numerous diseases as well as surgery, where the tension of the retina can result in tissue detachment during cutting. However, measuring the elasticity of adult retina wholemounts is difficult and until now only the mechanical properties at the surface have been characterized with micrometer resolution. Many processes, however, such as pathological changes prone to cause tissue rupture and detachment, respectively, are reflected in variations of retina elasticity at smaller length scales at the protein level. In the present work we demonstrate that freely oscillating cantilevers composed of nanostructured TiO2 scaffolds can be employed to study the frequency-dependent mechanical response of adult mammalian retina explants at the nanoscale. Constituting highly versatile scaffolds with strong tissue attachment for long-term organotypic culture atop, these scaffolds perform damped vibrations as fingerprints of the mechanical tissue properties that are derived using finite element calculations. Since the tissue adheres to the nanostructures via constitutive proteins on the photoreceptor side of the retina, the latter are stretched and compressed during vibration of the underlying scaffold. Probing mechanical response of individual proteins within the tissue, the proposed mechanical spectroscopy approach opens the way for studying tissue mechanics, diseases and the effect of drugs at the protein level.

  10. Signals for color and achromatic contrast in the goldfish inner retina.

    Burkhardt, Dwight A


    A moving stimulus paradigm was designed to investigate color contrast encoding in the retina. Recently, this paradigm yielded suggestive evidence for color contrast encoding in zebrafish but the significance and generality remain uncertain since the properties of color coding in the zebrafish inner retina are largely unknown. Here, the question of color contrast is pursued in the goldfish retina where there is much accumulated evidence for retinal mechanisms of color vision and opponent color-coding, in particular. Recordings of a sensitive local field potential of the inner retina, the proximal negative response, were made in the intact, superfused retina in the light-adapted state. Responses to color contrast and achromatic contrast were analyzed by comparing responses to a green moving bar on green versus red backgrounds. The quantitative form of the irradiance/response curves was distinctly different under a range of conditions in 32 retinas, thereby providing robust evidence for red-green color contrast. The color contrast is based on successive contrast, occurs in the absence of overt color opponency, and clearly differs from previous findings in the goldfish retina for simultaneous color contrast mediated by color-opponent neurons. The form of the irradiance/response curves suggests that successive color contrast is particularly important when achromatic contrast is low, as often occurs in natural environments. The present results provide a parallel with the well-known principle of human color vision, first proposed by Kirschmann as the third law of color contrast, and may also have implications for the evolution of vertebrate color vision.

  11. Prox1 Is a Marker for AII Amacrine Cells in the Mouse Retina

    Luis Pérez de Sevilla Müller


    Full Text Available The transcription factor Prox1 is expressed in multiple cells in the retina during eye development. This study has focused on neuronal Prox1 expression in the inner nuclear layer (INL of the adult mouse retina. Prox1 immunostaining was evaluated in vertical retinal sections and whole mount preparations using a specific antibody directed to the C-terminus of Prox1. Strong immunostaining was observed in numerous amacrine cell bodies and in all horizontal cell bodies in the proximal and distal INL, respectively. Some bipolar cells were also weakly immunostained. Prox1-immunoreactive amacrine cells expressed glycine, and they formed 35 ± 3% of all glycinergic amacrine cells. Intracellular Neurobiotin injections into AII amacrine cells showed that all gap junction-coupled AII amacrine cells express Prox1, and no other Prox1-immunostained amacrine cells were in the immediate area surrounding the injected AII amacrine cell. Prox1-immunoreactive amacrine cell bodies were distributed across the retina, with their highest density (3887 ± 160 cells/mm2 in the central retina, 0.5 mm from the optic nerve head, and their lowest density (3133 ± 350 cells/mm2 in the mid-peripheral retina, 2 mm from the optic nerve head. Prox1-immunoreactive amacrine cell bodies comprised ~9.8% of the total amacrine cell population, and they formed a non-random mosaic with a regularity index (RI of 3.4, similar to AII amacrine cells in the retinas of other mammals. Together, these findings indicate that AII amacrine cells are the predominant and likely only amacrine cell type strongly expressing Prox1 in the adult mouse retina, and establish Prox1 as a marker of AII amacrine cells.

  12. RETINA-specific expression of Kcnv2 is controlled by cone-rod homeobox (Crx) and neural retina leucine zipper (Nrl).

    Aslanidis, Alexander; Karlstetter, Marcus; Walczak, Yana; Jägle, Herbert; Langmann, Thomas


    Cone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive disorder that leads to progressive retinal degeneration with a distinct electroretinogram (ERG) phenotype. CDSRR patients show reduced sensitivity to dim light, augmented response to suprathreshold light and reduced response to flicker. The disorder is caused by mutations in the KCNV2 gene, which encodes the Kv11.1 subunit of a voltage-gated potassium channel. Here, we studied the retina-specific expression and cis-regulatory activity of the murine Kcnv2 gene using electroporation of explanted retinas. Using qRT-PCR profiling of early postnatal retinas, we showed that Kcnv2 expression increased towards P14, which marks the beginning of visual activity in mice. In vivo electroporation of GFP-Kcnv2 expressing plasmids revealed that Kv11.1 localizes to the inner segment membranes of adult P21 photoreceptors. Using bioinformatic prediction and chromatin immunoprecipitation (ChIP), we identified two Crx binding sites (CBS) and one Nrl binding site (NBS) in the Kcnv2 promoter. Reporter electroporation of the wild type promoter region induced strong DsRed expression, indicating high regulatory activity, whereas shRNA-mediated knockdown of Crx and Nrl resulted in reduced Kcnv2 promoter activity and low endogenous Kcnv2 mRNA expression in the retina. Site-directed mutagenesis of the CBS and NBS demonstrated that CBS2 is crucial for Kcnv2 promoter activity. We conclude that nucleotide changes in evolutionary conserved CBS could impact retina-specific expression levels of Kcnv2.

  13. Morphological Characterization and Topographic Analysis of Multiple Photoreceptor Types in the Retinae of Mesopelagic Hatchetfishes with Tubular Eyes

    Biagioni, Lauren M.; Hunt, David M.; Collin, Shaun P.


    Marine hatchetfishes, Argyropelecus spp., are one of the 14 genera of mesopelagic teleosts, which possess tubular eyes. The tubular eyes are positioned dorsally on the head and consist of a main retina, which subtends a large dorsal binocular field, and an accessory retina, which subtends the lateral monocular visual field. The topographic distribution of photoreceptors in the retina of Argyropelecus sladeni, Argyropelecus affinis, and Argyropelecus aculeatus was determined using a random, un...

  14. Microglia in the Outer Retina and their Relevance to Pathogenesis of Age-Related Macular Degeneration (AMD)


    Age-related macular degeneration (AMD), the largest cause of legal blindness in the elderly in the Western world, is a disease whose pathogenesis is incompletely understood and for which therapeutic challenges remain. The etiology of AMD is thought to involve chronic neuroinflammation of the retina but the details of relevant cellular mechanisms are still not fully understood. Retinal microglia are the primary resident immune cell in the retina and are normally absent from the outer retina, t...

  15. Oxygen Supply from the Bird's Eye Perspective: GLOBIN E IS A RESPIRATORY PROTEIN IN THE CHICKEN RETINA*♦

    Blank, Miriam; Kiger, Laurent; Thielebein, Anke; Gerlach, Frank; Hankeln, Thomas; Marden, Michael C.; Burmester, Thorsten


    The visual process in the vertebrate eye requires high amounts of metabolic energy and thus oxygen. Oxygen supply of the avian retina is a challenging task because birds have large eyes, thick retinae, and high metabolic rates but neither deep retinal nor superficial capillaries. Respiratory proteins such as myoglobin may enhance oxygen supply to certain tissues, and thus the mammalian retina harbors high amounts of neuroglobin. Globin E (GbE) was recently identified as an eye-specific globin...

  16. Somatostatin-14 and somatostatin-28 levels are light-driven and vary during development in the chicken retina.

    Dowton, M; Boelen, M K; Morgan, I G


    The relative levels of somatostatin-14 and somatostatin-28 were determined during both perinatal development and variations in lighting conditions in the chicken retina. During perinatal development of the retina, somatostatin-14 predominated in recently hatched chickens, whereas somatostatin-28 predominated in the retinas of older chickens. In mature chickens, the levels of both somatostatin-14 and somatostatin-28 increased during the light and decreased during the dark. Our results suggest that these two forms of somatostatin are released proportionally and in parallel.

  17. Spatiotemporal realization of an artificial retina model and performance evaluation through ISI- and spike count-based image reconstruction methods


    Development of an artificial retina model that can mimic the biologic retina is a highly challenging task and this task is an important step in the development of a visual prosthesis. The receptive field structure of the retina layer is usually modeled as a 2D difference of Gaussian (DOG) filter profile. In the present study, as a different approach, a retina model including a 3D 2-stage DOG filter (3D-ADOG) that has an adaptively changing bandwidth with respect to the local image stati...



    Objective To study the effect of fundus pigment on the response of the retina to transpupillary thermotherapy (TTT). Methods The retina were irradiated with 810 nm diode laser in 16 eyes of 8 pigmented rabbits and 12 eyes of 6 albino rabbits. The spot size was 1.2 mm; the duration was 60 s; and powers were 50, 80, 150 and 300 mW for pigmented rabbits and 800, 1 200 and 1 500mW for albino rabbits. All of the eyes were followed up with ophthalmolscope. The fundus was photographed and examined histologically with optic microscope immediately and 1 month after TTT respectively. Results The changes of the fundus and the histological examination were not significant immediately and 1 month after TTT in 50 mW group of pigmented rabbit and 800 mW of albino rabbit. Grey spot on the retina was observed on the fundus in 80 mW group of pigmented rabbit and 1 200 mW of albino rabbit immediately after TTT. The structure of the retina remained intact and subretinal fluid was observed histologically. Grey spot was still visible on the fundus, though the fluid was absorbed after 1 month. As the power of diode laser was increased to 150 mW for pigmented rabbits and 1500 mW for albino rabbit, fundus white spots were observed and the outer retina was destroyed while photoreceptors existed immediately after TTT. Pigmentation was found in white lesions and the fibrous proliferation was found in choroid 1 month after TTT. Prominent white spot was seen on the fundus immediately after laser irradiation of 300 mW in pigmented rabbits and the structure of the retina was obscured. One month after TTT, dense pigmentation appeared at laser lesions. The retina was thinner. There was prominent fibrous proliferation in the choroid. Conclusion The fundus pigment seems to play an important role in the response of the retina to TTT. The reaction of the retina is in proportion to the intensity of laser.

  19. Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes.

    Hernández-Ramírez, Ernesto; Sánchez-Chávez, Gustavo; Estrella-Salazar, Luis A; Salceda, Rocío


    Nitric oxide is a multifunctional molecule that can modify proteins via nitrosylation; it can also initiate signaling cascades through the activation of soluble guanylate cyclase. Diabetic retinopathy is the leading cause of blindness, but its pathogenesis is unknown. Multiple mechanisms including oxidative-nitrosative stress have been implicated. Our main goal was to find significant changes in nitric oxide (NO) levels and determine their association with nitrosative stress in the rat retina at the onset of diabetes. Diabetes was induced by a single intraperitoneal administration of streptozotocin. The possible nitric oxide effects on the rat retina were evaluated by the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a specific marker for NO-producing neurons, detected by histochemistry performed on whole retinas and retina sections. Immunohistochemistry was also performed on retina sections for iNOS, 3-nitrotyrosine (3-NT) and glial fibrillary acidic protein (GFAP). Retinal nitric oxide levels were assessed by measuring total nitrate/nitrite concentrations. Retinal cGMP levels were determined by radioimmunoassay. Western blots for nitrotyrosine (3-NT) and oxidized proteins were performed. In the present study, we found increased activity of NADPH-diaphorase and iNOS immunoreactivity in the rat retina at the onset of diabetes; this increase correlated with a remarkable increase in NO levels as early as 7 days after the onset of diabetes. However, cGMP levels were not modified by diabetes, suggesting that NO did not activate its signaling cascade. Even so, Western blots revealed a progressive increase in nitrated proteins at 7 days after diabetes induction. Likewise, positive nitrotyrosine immunolabeling was observed in the photoreceptor layer, ganglion cell layer, inner nuclear layer and some Müller cell processes in the retinas of diabetic rats. In addition, levels of oxidized proteins were increased in the retina early after

  20. From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium.

    Reichman, Sacha; Terray, Angélique; Slembrouck, Amélie; Nanteau, Céline; Orieux, Gaël; Habeler, Walter; Nandrot, Emeline F; Sahel, José-Alain; Monville, Christelle; Goureau, Olivier


    Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease.

  1. Identification of Novel Regulators of atonal Expression in the Developing Drosophila Retina

    Melicharek, David; Shah, Arpit; DiStefano, Ginnene; Gangemi, Andrew J.; Orapallo, Andrew; Vrailas-Mortimer, Alysia D.; Marenda, Daniel R.


    Atonal is a Drosophila proneural protein required for the proper formation of the R8 photoreceptor cell, the founding photoreceptor cell in the developing retina. Proper expression and refinement of the Atonal protein is essential for the proper formation of the Drosophila adult eye. In vertebrates, expression of transcription factors orthologous to Drosophila Atonal (MATH5/Atoh7, XATH5, and ATH5) and their progressive restriction are also involved in specifying the retinal ganglion cell, the founding neural cell type in the mammalian retina. Thus, identifying factors that are involved in regulating the expression of Atonal during development are important to fully understand how retinal neurogenesis is accomplished. We have performed a chemical mutagenesis screen for autosomal dominant enhancers of a loss-of-function atonal eye phenotype. We report here the identification of five genes required for proper Atonal expression, three of which are novel regulators of Atonal expression in the Drosophila retina. We characterize the role of the daughterless, kismet, and roughened eye genes on atonal transcriptional regulation in the developing retina and show that each gene regulates atonal transcription differently within the context of retinal development. Our results provide additional insights into the regulation of Atonal expression in the developing Drosophila retina. PMID:18832354


    David Križaj


    Full Text Available Background. At least twice daily our retinas move between a light adapted, cone-dominated (photopic state and a dark-adapted, color-blind and highly light-sensitive roddominated (scotopic state. In between is a rather ill-defined transitional state called the mesopic state in which retinal circuits express both rod and cone signals. Consequently, in the mesopic state the retinal output to the brain contained in the firing patterns of the ganglion cells consists of information derived from both rod and cone signals. Morphology, physiology and psychophysics all contributed to an understanding that the two systems are not independent but interact extensively via both pooling and mutual inhibition. This review lays down a rationale for such rod-cone interactions in the vertebrate retinas. It suggests that the important functional roles of rod-cone interactions is in that they shorten the duration of the mesopic state. As a result, the retina is maintained in either in the (rod-dominated high sensitivity photon counting mode or in the second mode which emphasizes temporal transients and spatial resolution (the cone-dominated photopic state.Conclusions. Experimental evidence for pre- and postsynaptic mixing of rod and cone signals in the retina is shown together with the preeminent neuromodulatory role of both light and dopamine in controling inter-actions between rod and cone signals. Dopamine is shown to be both necessary and sufficient to mediate light adaptation in the retina.

  3. Retinal degeneration progression changes lentiviral vector cell targeting in the retina.

    Maritza Calame

    Full Text Available In normal mice, the lentiviral vector (LV is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM. Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/- mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina.

  4. New developments in eye models with retina tissue phantoms for ophthalmic optical coherence tomography

    Rowe, T. Scott; Zawadzki, Robert J.


    We document our latest work in developing eye models with solid-state retinal tissue phantoms designed for demonstrating, validating and comparing ophthalmic Optical Coherence Tomography (OCT) instruments. Eye models with retina tissue phantoms can serve a variety of purposes, including demonstrating OCT functionality and performance in both the clinic and exhibit hall, validating retina layer thickness measurements from different commercial OCT instruments and as an aide for the R&D engineer and field service technician in the development and repair of instruments, respectively. The ideal eye model for OCT, the optical cross-sectional imaging modality, would have a volumetric morphology and scattering and absorption properties similar to that of normal human retina. These include a multi-layered structure of equivalent thickness to nominal human retina layers, a foveal pit that can be used to orient the image, and a RPE/OS and choroid like layers to demonstrate the depth penetration of the OCT system. A solid state tissue phantom relieves the user of constant cleaning and maintenance associated with the more common water bath model eyes. Novel processes12 have been developed to create retinal layers model that closely mimic the reflectance and scattering coefficients of the real layers of the retina, as imaged by spectral bandwidth of OCT.

  5. Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

    Vancura, Patrick; Wolloscheck, Tanja; Baba, Kenkichi; Tosini, Gianluca; Iuvone, P. Michael; Spessert, Rainer


    The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy—one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (Acadm) to display daily rhythms with peak values during daytime in preparations of the whole retina and microdissected photoreceptors. The cycling of both enzymes persisted in constant darkness, was dampened in mice deficient for dopamine D4 (D4) receptors and was altered in db/db mice—a model of diabetic retinopathy. The data of the present study are consistent with circadian clock-dependent and dopaminergic regulation of fatty acid oxidation in retina and its putative disturbance in diabetic retina. PMID:27727308

  6. The lens controls cell survival in the retina: Evidence from the blind cavefish Astyanax.

    Strickler, Allen G; Yamamoto, Yoshiyuki; Jeffery, William R


    The lens influences retinal growth and differentiation during vertebrate eye development but the mechanisms are not understood. The role of the lens in retinal growth and development was studied in the teleost Astyanax mexicanus, which has eyed surface-dwelling (surface fish) and blind cave-dwelling (cavefish) forms. A lens and laminated retina initially develop in cavefish embryos, but the lens dies by apoptosis. The cavefish retina is subsequently disorganized, apoptotic cells appear, the photoreceptor layer degenerates, and retinal growth is arrested. We show here by PCNA, BrdU, and TUNEL labeling that cell proliferation continues in the adult cavefish retina but the newly born cells are removed by apoptosis. Surface fish to cavefish lens transplantation, which restores retinal growth and rod cell differentiation, abolished apoptosis in the retina but not in the RPE. Surface fish lens deletion did not cause apoptosis in the surface fish retina or affect RPE differentiation. Neither lens transplantation in cavefish nor lens deletion in surface fish affected retinal cell proliferation. We conclude that the lens acts in concert with another optic component, possibly the RPE, to promote retinal cell survival. Accordingly, deficiency in both optic structures may lead to eye degeneration in cavefish.

  7. Presence and distribution of histaminergic components in rat and bovine retina.

    Arbonés, L; García-Verdugo, J; Picatoste, F; García, A


    The presence of histamine and its related enzymes, histidine decarboxylase and histamine N-methyltransferase and the subcellular distribution of the amine and of H(1)-receptors were studied in the retina of two mammalian species. Histamine is present in rat and bovine retinas in concentrations (113 +/- 10 and 72 +/- 9 ng/g wet tissue, respectively) similar to those found in the brain. Histological examination and release experiments with Compound 48/80 performed in rat retina indicate a non mast cell location for the amine. Histidine decarboxylase and histamine N-methyltransferase activities in rat and bovine retinas were also comparable to those found in brain cortex suggesting that histamine can be synthesized and catabolyzed in situ. Subcellular fractionation of bovine retina showed that both the amine and H(1)-receptors are concentrated in particulate fractions where small sized synaptosomes sediment, presumably derived from horizontal and amacrine cells. These results are in agreement with a neurotransmitter or neuromodulator role for histamine in cells of the retinal inner nuclear layer.

  8. Light-dark condition regulates sirtuin mRNA levels in the retina.

    Ban, Norimitsu; Ozawa, Yoko; Inaba, Takaaki; Miyake, Seiji; Watanabe, Mitsuhiro; Shinmura, Ken; Tsubota, Kazuo


    Sirtuins (Sirt1-7) are nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases/ADP-ribosyltransferases that modulate many metabolic responses affecting aging. Sirtuins expressed in tissues and organs involved in systemic metabolism have been extensively studied. However, the characteristics of sirtuins in the retina, where local energy expenditure changes dynamically in response to light stimuli, are largely unknown. Here we analyzed sirtuin mRNA levels by real-time PCR, and found that all seven sirtuins are highly expressed in the retina compared with other tissues, such as liver. We then analyzed the sirtuin mRNA profiles in the retina over time, under a 12-h light/12-h dark cycle (LD condition) and in constant darkness (DD condition). All seven sirtuins showed significant daily variation under the LD condition, with all except Sirt6 being increased in the dark phase. The expression patterns were different under the DD condition, suggesting that sirtuin mRNA levels except Sirt6 are affected by light-dark condition. These findings were not obtained in the brain and liver. In addition, the mRNA expression patterns of Nicotinamide phosphoribosyltransferase (Nampt), peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and transcription factor A, mitochondrial (Tfam) in the retina, were similar to those of the sirtuins except Sirt6. Our observations provide new insights into the metabolic mechanisms of the retina and the sirtuins' regulatory systems.

  9. Spatiotemporal distribution of 1P1 antigen expression in the plexiform layers of developing chick retina



    Changes in the distribution of 1P1-antigen in the developing chick retina have been examined by indriect immunofluorescence staining technique using the novel monoclonal antibody(MAb)1P1.Expression of the 1P1 antigen was found to be regulated in radial as well as in tangential dimension of the retina,being preferentially or exclusively located in the inner and outer plexiform layers of the neural retina depending on the stages of development ,With the onset of the formation of the inner plexiform layer 1P1 antigen becomes expressed in the retina.With progressing differentiation of the inner plexiform layer 1P1 immunofluorescence revealed 2 subbands at E9 and 6 subands at E18,At postnatal stages(after P3) immunoreactivity was reduced in an inside-outside sequence leading to the complete absence of the 1P1 antigen in adulthood.1P1 antigen expression in the outer plexiform layer was also subject to developmental regulation.The spation-temporal pattern of 1P1 antigen expression was correlated with the time course of histological differentation of chick retina,namely the synapse rich plexiform layers.Whether the 1P1 antigen was functionally involved in dendrite extension and synapse formation was discussed.

  10. Zebrafish Cx35: cloning and characterization of a gap junction gene highly expressed in the retina.

    McLachlan, Elizabeth; White, Thomas W; Ugonabo, Chioma; Olson, Carl; Nagy, James I; Valdimarsson, Gunnar


    The vertebrate connexin gene family encodes protein subunits of gap junction channels, which provide a route for direct intercellular communication. Consequently, gap junctions play a vital role in many developmental and homeostatic processes. Aberrant functioning of gap junctions is implicated in many human diseases. Zebrafish are an ideal vertebrate model to study development of the visual system as they produce transparent embryos that develop rapidly, thereby facilitating morphological and behavioral testing. In this study, zebrafish connexin35 has been cloned from a P1 artificial chromosome (PAC) library. Sequence analysis shows a high degree of similarity to the Cx35/36 orthologous group, which are expressed primarily in nervous tissue, including the retina. The gene encodes a 304-amino acid protein with a predicted molecular weight of approximately 35 kDa. Injection of zebrafish Cx35 RNA into paired Xenopus oocytes elicited intercellular electrical coupling with weak voltage sensitivity. In development, Cx35 is first detectable by Northern analysis and RT-PCR, at 2 days post-fertilization (2 dpf), and in the adult it is expressed in the brain and retina. Immunohistochemical analysis revealed that the Cx35 protein is expressed in two sublaminae of the inner plexiform layer of the adult retina. A similar pattern was seen in the 4 and 5 dpf retina, but no labeling was detected in the retina of earlier embryos.

  11. Changes in growth factor expression in normal aging of the rat retina.

    Smith, Christopher P; Steinle, Jena J


    Although much is known about the growth factor changes in ocular tissues during various diseases, little is known about normal aging of the retina. In order to further understand normal aging in the retina, we characterized age-related changes of growth factor expression in three different ages of rat retina. Real time PCR and protein analysis was conducted to investigate steady state mRNA expression and protein levels of VEGF, VEGFR2, PEDF, Ang-1, Tie-2, EphB4 and ephrinB2 in the retina of 8-, 22-, and 32-month-old Brown Norway X Fischer 344 F1 hybrid rats. An increase of VEGF protein levels was found at 32months compared to 8 and 22months of age. VEGFR2 protein was found to be increased at 22 and 32months compared to 8months. PEDF protein levels were reduced at 22 and 32months. Tie-2 levels were found to be significantly decreased by 32months compared to 8months of age, while ephrinB2 was found to be significantly lower at both 22 and 32months compared to 8months of age. The increases found in VEGF and its receptor VEGFR2, with the simultaneous decrease of PEDF protein levels, may stimulate an environment that is well suited for neovascularization in the normal aging retina. Overall, these results suggest that normal aging produces substantial changes in gene expression and protein levels.

  12. Long-term glial reactivity in rat retinas ipsilateral and contralateral to experimental glaucoma.

    Kanamori, Akiyasu; Nakamura, Makoto; Nakanishi, Yoriko; Yamada, Yuko; Negi, Akira


    Although glaucoma is known to alter glial reactivity, the long-term effect of elevated intraocular pressure (IOP) on glial change has not been fully elucidated. This study aimed to examine how chronically elevated IOP induced by episcleral vein cauterization (EVC) in unilateral eyes affect reactivities of astrocytes and Müller cells of rats in the treated as well as contralateral eyes over time. EVC in unilateral eyes of Sprague-Dawley rats were performed to produce chronically elevated IOP. Flat mounted retina preparations were made at several points until 6 months, which were subjected to immunostaining for glial fibrillary acidic protein (GFAP). Retinal homogenates were one- or two-dimensionally electrophoresed, followed by GFAP immunoblotting. EVC significantly increased IOPs up to 27.8 from 13.1 mmHg, which gradually decreased over time. In flat mounted retinas, astrocytes lost but Müller cells gained GFAP immunoreactivity at 3 days after cauterization. The glial changes were partially reversed over time but last even after IOP normalization. In the contralateral eyes, similar glial changes gradually appeared at 1 month after EVC and thereafter. Immunoblotting demonstrated not only molecular size shifts but also alteration of isoelectric focusing of GFAP both in treated and contralateral retina as compared with age-matched control retina. EVC led to opposite reactions in astrocytes and Müller cells in terms of GFAP immunoreactivity. Late-onset glial reactivity also occurred in the contralateral retina.

  13. Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

    Reinhard, Jacqueline; Renner, Marina; Wiemann, Susanne; Shakoor, Daniel A.; Stute, Gesa; Dick, H. Burkhard; Faissner, Andreas; Joachim, Stephanie C.


    Retinal ischemia occurs in a variety of eye diseases. Restrained blood flow induces retinal damage, which leads to progressive optic nerve degeneration and vision loss. Previous studies indicate that extracellular matrix (ECM) constituents play an important role in complex tissues, such as retina and optic nerve. They have great impact on de- and regeneration processes and represent major candidates of central nervous system glial scar formation. Nevertheless, the importance of the ECM during ischemic retina and optic nerve neurodegeneration is not fully understood yet. In this study, we analyzed remodeling of the extracellular glycoproteins fibronectin, laminin, tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans (CSPGs) aggrecan, brevican and phosphacan/RPTPβ/ζ in retinae and optic nerves of an ischemia/reperfusion rat model via quantitative real-time PCR, immunohistochemistry and Western blot. A variety of ECM constituents were dysregulated in the retina and optic nerve after ischemia. Regarding fibronectin, significantly elevated mRNA and protein levels were observed in the retina following ischemia, while laminin and tenascin-C showed enhanced immunoreactivity in the optic nerve after ischemia. Interestingly, CSPGs displayed significantly increased expression levels in the optic nerve. Our study demonstrates a dynamic expression of ECM molecules following retinal ischemia, which strengthens their regulatory role during neurodegeneration. PMID:28262779

  14. Patterns of cell proliferation and rod photoreceptor differentiation in shark retinas.

    Ferreiro-Galve, Susana; Rodríguez-Moldes, Isabel; Anadón, Ramón; Candal, Eva


    We studied the pattern of cell proliferation and its relation with photoreceptor differentiation in the embryonic and postembryonic retina of two elasmobranchs, the lesser spotted dogfish (Scyliorhinus canicula) and the brown shyshark (Haploblepharus fuscus). Cell proliferation was studied with antibodies raised against proliferating cell nuclear antigen (PCNA) and phospho-histone-H3, and early photoreceptor differentiation with an antibody raised against rod opsin. As regards the spatiotemporal distribution of PCNA-immunoreactive cells, our results reveal a gradual loss of PCNA that coincides in a spatiotemporal sequence with the gradient of layer maturation. The presence of a peripheral growth zone containing pure-proliferating retinal progenitors (the ciliary marginal zone) in the adult retina matches with the general pattern observed in other groups of gnathostomous fishes. However, in the shark retina the generation of new cells is not restricted to the ciliary marginal zone but also occurs in retinal areas that contain differentiated cells: (1) in a transition zone that lies between the pure-proliferating ciliary marginal zone and the central (layered) retina; (2) in the differentiating central area up to prehatching embryos where large amounts of PCNA-positive cells were observed even in the inner and outer nuclear layers; (3) and in the retinal pigment epithelium of prehatching embryos. Rod opsin immunoreactivity was observed in both species when the outer plexiform layer begins to be recognized in the central retina and, as we previously observed in trout, coincided temporally with the weakening in PCNA labelling.

  15. The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium

    Goetz Thomas


    Full Text Available Abstract Background The mammalian retina is a valuable model system to study neuronal biology in health and disease. To obtain insight into intrinsic processes of the retina, great efforts are directed towards the identification and characterization of transcripts with functional relevance to this tissue. Results With the goal to assemble a first genome-wide reference transcriptome of the adult mammalian retina, referred to as the retinome, we have extracted 13,037 non-redundant annotated genes from nearly 500,000 published datasets on redundant retina/retinal pigment epithelium (RPE transcripts. The data were generated from 27 independent studies employing a wide range of molecular and biocomputational approaches. Comparison to known retina-/RPE-specific pathways and established retinal gene networks suggest that the reference retinome may represent up to 90% of the retinal transcripts. We show that the distribution of retinal genes along the chromosomes is not random but exhibits a higher order organization closely following the previously observed clustering of genes with increased expression. Conclusion The genome wide retinome map offers a rational basis for selecting suggestive candidate genes for hereditary as well as complex retinal diseases facilitating elaborate studies into normal and pathological pathways. To make this unique resource freely available we have built a database providing a query interface to the reference retinome 1.

  16. The mouse retina in 3D: quantification of vascular growth and remodeling.

    Milde, Florian; Lauw, Stephanie; Koumoutsakos, Petros; Iruela-Arispe, M Luisa


    The mouse retina has become a prominent model for studying angiogenesis. The easy access and well-known developmental progression have significantly propelled our ability to examine and manipulate blood vessels in vivo. Nonetheless, most studies have restricted their evaluations to the superficial plexus (an upper vascular layer in contact with the vitreous). Here we present experimental data and quantification for the developmental progression of the full retina including the intermediate and deeper plexus that sprouts from the superficial layer. We analyze the origin and advancement of vertical sprouting and present the progression of vascular perfusion within the tissue. Furthermore, we introduce the use of Minkowsky functionals to quantify remodeling in the superficial and deeper plexus. The work expands information on the retina towards a 3D structure. This is of particular interest, as recent data have demonstrated differential effects of gene deletion on the upper and deeper plexus, highlighting the concept of distinct operational pathways during sprouting angiogenesis.

  17. The sarcoglycan-sarcospan complex localization in mouse retina is independent from dystrophins

    Fort, Patrice; Estrada, Francisco-Javier; Bordais, Agnès; Mornet, Dominique; Sahel, José-Alain; Picaud, Serge; Vargas, Haydeé Rosas; Coral-Vázquez, Ramón M.; Rendon, Alvaro


    The sarcoglycan–sarcospan (SG–SSPN) complex is part of the dystrophin-glycoprotein complex that has been extensively characterized in muscle. To establish the framework for functional studies of sarcoglycans in retina here, we quantified sarcoglycans mRNA levels with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and performed immunohistochemistry to determine their cellular and subcellular distribution. We showed that the β-, δ-, γ-, ε-sarcoglycans and sarcospan are expressed in mouse retina. They are localized predominantly in the outer and the inner limiting membranes, probably in the Müller cells and also in the ganglion cells axons where the expression of dystrophins have never been reported. We also investigated the status of the sarcoglycans in the retina of mdx3cv mutant mice for all Duchene Muscular Dystrophy (DMD) gene products. The absence of dystrophin did not produce any change in the sarcoglycan–sarcospan components expression and distribution. PMID:15993965

  18. Rod photoreceptors express GPR55 in the adult vervet monkey retina

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian


    Cannabinoids exert their actions mainly through two receptors, the cannabinoid CB1 receptor (CB1R) and cannabinoid CB2 receptor (CB2R). In recent years, the G-protein coupled receptor 55 (GPR55) was suggested as a cannabinoid receptor based on its activation by anandamide and tetrahydrocannabinol...... components (Müller cells). The aim of this study was to determine the expression pattern of GPR55 in the monkey retina by using confocal microscopy. Our results show that GPR55 is strictly localized in the photoreceptor layer of the extrafoveal portion of the retina. Co-immunolabeling of GPR55 with rhodopsin......, the photosensitive pigment in rods, revealed a clear overlap of expression throughout the rod structure with most prominent staining in the inner segments. Additionally, double-label of GPR55 with calbindin, a specific marker for cone photoreceptors in the primate retina, allowed us to exclude expression of GPR55...

  19. [Role of immunological factors in peripheral vitreo-chorioretinal dystrophies and macular ruptures of the retina].

    Balashova, L M; Saksonova, E O; Zaĭtseva, N S; Slepova, O S; Teplinskaia, L E; Il'nitskiĭ, V V; Grishin, V L


    The authors analyze the results of clinical and immunological examinations of patients with peripheral vitreo-chorioretinal dystrophies (PVCRD) and macular ruptures of the retina. No antibodies to S-AG were detected in the lacrimal fluid in 87.5% of patients with PVCRD without retinal defects. In patients with PVCRD with retinal defects antibodies to S-AG were detected in 70% of cases. These antibodies were absent in the patients with macular ruptures of the retina. In none of the patients were these antibodies detected in the blood serum. The levels of circulating immune complexes were normal in the patients PVCRD and increased in those with macular ruptures of the retina. These data permit a hypothesis on the development of local autoimmune reactions in PVCRD patients in response to the appearance of AG of the injured tissues.

  20. Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation

    Rountree, Corey M.; Inayat, Samsoon; Troy, John B.; Saggere, Laxman


    Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.

  1. Sobre la terapia génica para enfermedades de la retina.

    Fischer, M Dominik


    Las mutaciones en un gran número de genes provocan degeneración de la retina y ceguera sin que exista actualmente cura alguna. En las últimas décadas, la terapia génica para enfermedades de la retina ha evolucionado y se ha convertido en un nuevo y prometedor paradigma terapéutico para estas enfermedades poco comunes. Este artículo refleja las ideas y los conceptos que parten de la ciencia básica hacia la aplicabilidad de la terapia génica en el ámbito clínico. Se describen los avances y las reflexiones actuales sobre la eficacia de los ensayos clínicos en la actualidad y se discuten los posibles obstáculos y soluciones de cara al futuro de la terapia génica para enfermedades de la retina. © 2017 S. Karger AG, Basel.

  2. Pharmacokinetic study of mangiferin in rat plasma and retina using high-performance liquid chromatography

    Hou, Yunlong; Fan, Shengjun; Gu, Yuanqin; Yu, Xuhui; Li, Baoxin


    Purpose Although the naturally occurring antioxidant mangiferin has been widely used, it is not yet known whether it can cross the blood-retina barrier (BRB) and enter the eye. The purpose of this experiment was to investigate the ability of mangiferin to pass the blood-retina barrier. Methods Sprague–Dawley rats were used for biologic fluid sampling after intravenous administration of mangiferin at doses of 10, 25, and 50 mg/kg. Blood and retina samples were collected at different time points post-dose. High-performance liquid chromatography (HPLC) separation was conducted on a COSMOSIL 5C18—MS—II column (4.6 mm×250 mm, 5 μm) with a flow rate of 1.0 ml/min using a mobile phase comprised of methanol −2% glacial acetic acid (40:60 v:v). Results The HPLC method has proven suitable to determine the presence of mangiferin in the eye. The plasma concentration of mangiferin was dose dependent. Pharmacokinetic parameters of mangiferin in plasma after intravenous administration were fitted to the two-compartment model with the first-order elimination and first-order transfer between central and peripheral compartments. The concentration of mangiferin in the retina goes with that in the blood. Mangiferin concentrations in the retina reached 5.69±1.48 μg/ml 0.5 h after intravenous administration (50 mg/kg) and then dropped gradually to 0.30±0.02 μg/ml 5.0 h later. The eye–to-plasma concentration ratio was 2.80%. Conclusions Mangiferin can pass the blood-retina barrier after a single intravenous administration and may be a potential natural antioxidant in treating eye diseases. PMID:20806037

  3. Training and professional profile of retinologists in Spain: Retina 2 project, Report 4

    Pastor JC


    Full Text Available J Carlos Pastor1,3, Itziar Fernández2, Jimena Rojas1, Rosa Coco1, Maria R Sanabria1, Enrique Rodríguez-de la Rúa1,3, Diego Sánchez3, Carmen Valverde3, Anna Sala Puigdollers1,31University Institute of Applied Ophthalmobiology (IOBA, Retina Group, 2Ministry of Science and Innovation CIBER-BBN, Statistics Department, 3Clinic University Hospital, University of Valladolid, Valladolid, SpainBackground: Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties.Methods: After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined.Results: Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%. Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5% practiced anterior segment surgery, and 78.7% declared skills in vitrectomy.Conclusion: We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.Keywords: clinical activity, fellowship, mastership, professional profile, retinologist training

  4. Disabled-1 is expressed in type AII amacrine cells in the mouse retina.

    Rice, D S; Curran, T


    The organization of several laminated structures in the brain is controlled by a signaling pathway activated by Reelin, a large glycoprotein secreted by pioneer neurons in the developing brain. Reelin binds to transmembrane receptors, including VLDLR and ApoER2, and stimulates tyrosine phosphorylation of Disabled-1 (Dab1), which associates with an NPxY motif present in the cytoplasmic domain of the receptors. Disruption of reelin, dab1, or both the vldr and apoer2 genes results in similar cell positioning defects in laminated brain regions including the cerebellum, hippocampus, and cerebral cortex. Although retinal ganglion cells express reelin during development, there is no obvious disruption of cell positioning in the retina of reeler mice. Here, we examine the expression pattern of Dab1 as a first step toward understanding the function of the Reelin signaling pathway in neural retina. Immunohistochemical analysis of the adult retina revealed that Dab1 is expressed in a specific type of amacrine cell. These cells display a narrow dendritic field and they project to two distinct sublaminae within the inner plexiform layer. Dab1 co-localizes with the high-affinity glycine transporter, indicating that these amacrine cells are glycinergic. Cells that express Dab1 are surrounded by dopaminergic fibers originating from wide-field amacrine cells. These features are characteristic of type AII amacrine cells described in other mammalian species. Analysis of the retina at several stages of development revealed that Dab1 is expressed shortly after birth during the time at which AII amacrine cells extend neurites and form synaptic connections in the inner retina. This raises the possibility that the Reelin/Dab1 signaling pathway contributes to formation of intraretinal circuitry in the neural retina. Copyright 2000 Wiley-Liss, Inc.

  5. Immunolocalisation pattern of complex I-V in ageing human retina: Correlation with mitochondrial ultrastructure.

    Nag, Tapas Chandra; Wadhwa, Shashi


    Earlier studies reported accumulation of mitochondrial DNA mutations in ageing and age-related macular degeneration. To know about the mitochondrial status with age, we examined immunoreactivity (IR) to markers of mitochondria (anti-mitochondrial antibody and voltage-dependent anion channel-1) and complex I-V (that mediate oxidative phosphorylation, OXPHOS) in donor human retinas (age: 19-94years; N=26; right eyes). In all samples, at all ages, IR to anti-mitochondrial antibody and voltage-dependent anion channel-1 was prominent in photoreceptor cells. Between second and seventh decade of life, strong IR to complex I-V was present in photoreceptors over macular to peripheral retina. With progressive ageing, the photoreceptors showed a decrease in complex I-IR (subunit NDUFB4) at eighth decade, and a weak or absence of IR in 10 retinas between ninth and tenth decade. Patchy IR to complex III and complex IV was detected at different ages. IR to ND1 (complex I) and complex II and V remained unaltered with ageing. Nitrosative stress (evaluated by IR to a nitro-tyrosine antibody) was found in photoreceptors. Superoxide dismutase-2 was found upregulated in photoreceptors with ageing. Mitochondrial ultrastructure was examined in two young retinas with intact complex IR and six aged retinas whose counterparts showed weak to absence of IR. Observations revealed irregular, photoreceptor inner segment mitochondria in aged maculae and mid-peripheral retina between eighth and ninth decade; many cones possessed autophagosomes with damaged mitochondria, indicating age-related alterations. A trend in age-dependent reduction of complex I-IR was evident in aged photoreceptors, whereas patchy complex IV-IR (subunits I and II) was age-independent, suggesting that the former is prone to damage with ageing perhaps due to oxidative stress. These changes in OXPHOS system may influence the energy budget of human photoreceptors, affecting their viability. Copyright © 2016 Elsevier B.V. and

  6. Transducin duplicates in the zebrafish retina and pineal complex: differential specialisation after the teleost tetraploidisation.

    David Lagman

    Full Text Available Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation.

  7. Transducin duplicates in the zebrafish retina and pineal complex: differential specialisation after the teleost tetraploidisation.

    Lagman, David; Callado-Pérez, Amalia; Franzén, Ilkin E; Larhammar, Dan; Abalo, Xesús M


    Gene duplications provide raw materials that can be selected for functional adaptations by evolutionary mechanisms. We describe here the results of 350 million years of evolution of three functionally related gene families: the alpha, beta and gamma subunits of transducins, the G protein involved in vision. Early vertebrate tetraploidisations resulted in separate transducin heterotrimers: gnat1/gnb1/gngt1 for rods, and gnat2/gnb3/gngt2 for cones. The teleost-specific tetraploidisation generated additional duplicates for gnb1, gnb3 and gngt2. We report here that the duplicates have undergone several types of subfunctionalisation or neofunctionalisation in the zebrafish. We have found that gnb1a and gnb1b are co-expressed at different levels in rods; gnb3a and gnb3b have undergone compartmentalisation restricting gnb3b to the dorsal and medial retina, however, gnb3a expression was detected only at very low levels in both larvae and adult retina; gngt2b expression is restricted to the dorsal and medial retina, whereas gngt2a is expressed ventrally. This dorsoventral distinction could be an adaptation to protect the lower part of the retina from intense light damage. The ontogenetic analysis shows earlier onset of expression in the pineal complex than in the retina, in accordance with its earlier maturation. Additionally, gnb1a but not gnb1b is expressed in the pineal complex, and gnb3b and gngt2b are transiently expressed in the pineal during ontogeny, thus showing partial temporal subfunctionalisation. These retina-pineal distinctions presumably reflect their distinct functional roles in vision and circadian rhythmicity. In summary, this study describes several functional differences between transducin gene duplicates resulting from the teleost-specific tetraploidisation.

  8. Rod photoreceptors express GPR55 in the adult vervet monkey retina.

    Joseph Bouskila

    Full Text Available Cannabinoids exert their actions mainly through two receptors, the cannabinoid CB1 receptor (CB1R and cannabinoid CB2 receptor (CB2R. In recent years, the G-protein coupled receptor 55 (GPR55 was suggested as a cannabinoid receptor based on its activation by anandamide and tetrahydrocannabinol. Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells and CB2R in glial components (Müller cells. The aim of this study was to determine the expression pattern of GPR55 in the monkey retina by using confocal microscopy. Our results show that GPR55 is strictly localized in the photoreceptor layer of the extrafoveal portion of the retina. Co-immunolabeling of GPR55 with rhodopsin, the photosensitive pigment in rods, revealed a clear overlap of expression throughout the rod structure with most prominent staining in the inner segments. Additionally, double-label of GPR55 with calbindin, a specific marker for cone photoreceptors in the primate retina, allowed us to exclude expression of GPR55 in cones. The labeling of GPR55 in rods was further assessed with a 3D visualization in the XZ and YZ planes thus confirming its exclusive expression in rods. These results provide data on the distribution of GPR55 in the monkey retina, different than CB1R and CB2R. The presence of GPR55 in rods suggests a function of this receptor in scotopic vision that needs to be demonstrated.

  9. Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina.

    Alexander Picker


    Full Text Available During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation.

  10. Gene expression and protein distribution of orexins and orexin receptors in rat retina.

    Liu, F; Xu, G Z; Wang, L; Jiang, S X; Yang, X L; Zhong, Y M


    Orexins, composed of orexin A and orexin B, are identified as endogenous ligands of two orphan G-protein-coupled receptors: orexin 1 and orexin 2 receptors (OX1R and OX2R). Orexins are implicated in regulating wake/sleep states, feeding behaviors, etc. Using reverse transcription-polymerase chain reactive (RT-PCR) analysis and immunofluorescence double labeling, we investigated the distributions of orexin A, orexin B, OX1R and OX2R in rat retina. RT-PCR analysis revealed the presence of mRNAs of prepro-orexin, OX1R and OX2R in rat retina. Immunostaining for orexin A and orexin B was observed in many cells in the inner nuclear layer and the ganglion cell layer. In the outer retina, horizontal cells, labeled by calbindin, and bipolar cells, labeled by homeobox protein Chx10, were orexin A- and orexin B-positive. In the inner retina, two orexins were both found in GABAergic amacrine cells (ACs), including dopaminergic and cholinergic ones, stained by tyrosine hydroxylase and choline acetyltransferase respectively. Glycinergic ACs, including AII ACs, also expressed orexins. Weak to moderate labeling for orexin A and orexin B was diffusely distributed in the inner plexiform layer. Additionally, orexins were expressed in almost all ganglion cells (GCs) retrogradely labeled by cholera toxin B subunit. Specifically, double-labeling experiments demonstrated that melanopsin-positive GCs (intrinsically photosensitive retinal GCs, ipRGCs) were labeled by two orexins. Morever, OX1R immunoreactivity was observed in most of GCs and all dopaminergic ACs, as well as in both outer and inner plexiform layers. In contrast, no obvious OX2R immunostaining was detectable in the rat retina. These results suggest that orexins may modulate the function of neurons, especially in the inner retina. We further hypothesize that the orexin signaling via ipRGCs may be involved in setting the suprachiasmatic nucleus (SCN) circadian clock.

  11. Surgical treatment in combined hamartoma of the retina and retinal pigment epithelium.

    Sánchez-Vicente, J L; Rueda-Rueda, T; Llerena-Manzorro, L; Molina-Socola, F E; Contreras-Díaz, M; Szewc, M; Vital-Berral, C; Alfaro-Juárez, A; Medina-Tapia, A; López-Herrero, F; González-García, L; Muñoz-Morales, A


    The case is presented of a 39 year-old man with a combined hamartoma of the retina and retinal pigment epithelium, who experienced progressive visual loss and worsening of metamorphopsia. The patient underwent vitrectomy and epiretinal component peeling, with improvement in visual acuity, metamorphopsia, and retinal architecture, assessed by optical coherence tomography. Selected patients with combined hamartomas of the retina and retinal pigment epithelium may benefit from surgical management. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Desprendimiento de retina regmatógeno. Actuación de Enfermería

    Domínguez Manzano, María


    El objetivo principal de este trabajo es, la realización y presentación con la recopilación e información actualizada en el desprendimiento de retina regmatógeno, para preparar los conocimientos teóricos y prácticos necesarios y poder realizar el trabajo diario con la mayor calidad posible. Los principales objetivos secundarios planteados son: 1. Conocer en qué consiste la patología del desprendimiento de retina y definir la etiología, patogenia, evolución, tratamiento y posibles compli...

  13. Design and realization of retina-like three-dimensional imaging based on a MOEMS mirror

    Cao, Jie; Hao, Qun; Xia, Wenze; Peng, Yuxin; Cheng, Yang; Mu, Jiaxing; Wang, Peng


    To balance conflicts for high-resolution, large-field-of-view and real-time imaging, a retina-like imaging method based on time-of flight (TOF) is proposed. Mathematical models of 3D imaging based on MOEMS are developed. Based on this method, we perform simulations of retina-like scanning properties, including compression of redundant information and rotation and scaling invariance. To validate the theory, we develop a prototype and conduct relevant experiments. The preliminary results agree well with the simulations.

  14. Rod Photoreceptors Express GPR55 in the Adult Vervet Monkey Retina

    Joseph Bouskila; Pasha Javadi; Christian Casanova; Maurice Ptito; Jean-François Bouchard


    Cannabinoids exert their actions mainly through two receptors, the cannabinoid CB1 receptor (CB1R) and cannabinoid CB2 receptor (CB2R). In recent years, the G-protein coupled receptor 55 (GPR55) was suggested as a cannabinoid receptor based on its activation by anandamide and tetrahydrocannabinol. Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its n...

  15. Pharmacological Protection of the Retina against Damaging Laser Exposures: A Feasibility Study


    because of its gelatinous nature in the rabbit, it could be gently removed without tearing the retina. Four or five radial cuts, each about 1-2 mm...Component mq/L uM L-glutamine 73 500 taurine 0.75 6 choline Cl 0.6 4.3 myo-inositol 27 150 Na pyruvate 22 200 ascorbate 18 100 glucose 1800 10,000...32,36,37). This difference could be due to a protective effect conferred by melanosomes in the retina, since the other natural anti-oxidant

  16. High resolution mosaic image of capillaries in human retina by adaptive optics

    Ning Ling; Yudong Zhang; Xuejun Rao; Cheng Wang; Yiyun Hu; Wenhan Jiang


    Adaptive optics (AO) has been proved as a powerful means for high resolution imaging of human retina.Because of the pixel number of charge-coupled device (CCD) camera, the field of view is limited to 1°.In order to have image of capillaries around vivo human fovea, we use mosaic method to obtain high resolution image in area of 6°× 6°. Detailed structures of capillaries around fovea with resolution of 2.3μm are clearly shown. Comparison shows that this method has a much higher resolution than current clinic retina imaging methods.

  17. A Comparative Analysis of the Endocannabinoid System in the Retina of Mice, Tree Shrews, and Monkeys

    Bouskila, Joseph; Javadi, Pasha; Elkrief, Laurent; Casanova, Christian; Bouchard, Jean-François; Ptito, Maurice


    The endocannabinoid (eCB) system is widely expressed in various parts of the central nervous system, including the retina. The localization of the key eCB receptors, particularly CB1R and CB2R, has been recently reported in rodent and primate retinas with striking interspecies differences. Little is known about the distribution of the enzymes involved in the synthesis and degradation of these eCBs. We therefore examined the expression and localization of the main components of the eCB system ...

  18. Cell therapeutics to treat diseases of the retina

    Natarajan S


    Full Text Available Background: The adult Bone Marrow Stem Cells (BMSCs have distinct advantages over the other types of stem cells. They are multipotent, can be stored for upto 10 years and considered to be one of the best sources of hematopoietic and mesenchymal stem cells in an adult body. Genetically inherited diseases such as Retinitis Pigmentosa and Degenerative diseases such as Age Related Macular Degeneration remain unsolved as no definitive treatment is available to repair the damages caused to the RPE and Photoreceptors as of now. In this scenario, the technique of Bone Marrow aspiration & isolation of Mono Nucleated Cells (MNCs & intra-vitreal injection of a very small volume of MNCs in human retinal disorders has been standardized and is safe and feasible for human studies (Mohanty et al and autotransplantation of RPEs from periphery to affected area are underpractice(Coffey et al. In this study we report our research work on different approaches to the above diseases using cell therapeuticsStudy 1 Materials & methods: Ciliary Pigment Epithelium was harvested from donor eyes from Aditya Jyot Eye Hospital, Mumbai and was taken to and grown at NCRM lab. The cells were grown in the earlier reported methodology of Brenda et al (Science 2004. Results: The CPE derived Retinal stem cells grew well in the lab. However, the practical difficulties of harvesting the same in patients limited our further steps in this study. Study II:? Materials & methods: Cadaver eye RPE cells were harvested and grown using polymer scaffolds after transporting them over 6 to 12 Hrs. The RPEs were grown on conventional methods and in polymer scaffolds and were subjected to RT-PCR. Results: Human RPEs were able to grow without amniotic membrane and the same was proven by RT-PCR. This would make it possible for the peripheral RPEs taken from patients to be stored and later expanded and used for replacing the diseased cells of the central portion of the retina in future, without having

  19. Comparative analysis of the expression of neural stem cell-associated genes during neocortex and retina development in human.

    Verdiev, B I; Milyushina, L A; Podgornyi, O V; Poltavtseva, R A; Zinov'eva, R D; Sukhikh, G T; Aleksandrova, M A


    We compared the expression of Sox2, Oct4, Nanog, Pax6, Prox1 genes associated with plasticity of neural stem and progenitor cells during human neocortex and retina development and in cell cultures. At the analyzed stages of neurogenesis, Pax6 gene is expressed in the neocortex and retina at constant levels, the expression is by one order of magnitude higher in the retina. The dynamics of Sox2 and Pax6 expression in the neocortex was similar. The expression of Oct4 and Nanog genes during neurogenesis in the neocortex and human fetal retina reflects the existence of a high-plasticity cell pool. The dynamics of βIII-tubulin expression indicates that the retina develops more rapidly than the neocortex. Our experiments showed that genetically determined cell potencies typical of native cells are realized in primary cultures without specific stimulation.

  20. Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

    Beach, Krista M.; Jianbo Wang; Otteson, Deborah C.


    In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransdu...

  1. From embryonic stem cells to retina%从胚胎干细胞到视网膜

    曹明哲; 陈舒怡


    Retinal degenerative diseases affect millions of people worldwide. However, retina in human has poor potential for regeneration to compensate for cell loss. Thus, cell replacement therapy is a promising strategy to ultimately cure retinal degenerative diseases. Embryonic stem cells (ES cells) are pluripotent cells and they can grow indefinitely and differentiate into derivatives of all three germ layers. These properties make ES cells promosing for cell replacement therapies. Nowadays, ES cells can be induced to differentiate into retinal cells, even the whole retinal tissue. Furthermore, ES derived retinal cells can integrate into host retina. In this review, we first briefly summarize the organizational structure, the development process and the regulatory mechanism of the mammalian retina, and then focus on the progress of differentiation of retinal cell and retinal tissue from ES and induced pluripotent stem cells.%视网膜退行性病变影响着全世界数百万人。然而,视网膜是人体再生能力很差的一类组织,成年机体无法自我更新那些病变中丢失的视网膜细胞,导致视网膜退行性病变的不可逆性。因此,恢复患者视觉将依赖于引入外源细胞替代丢失的视网膜神经元。胚胎干细胞(ES细胞)具有无限的自我更新能力和形成机体所有类型细胞的巨大分化潜力。这两个特性使得ES细胞成为细胞替代疗法的理想供体细胞。近年来,人们在探索将ES和诱导多能干细胞(iPS细胞)体外定向诱导分化为视网膜神经元,甚至整个视网膜方面已取得多项进展,并且体外形成的视网膜细胞可以与宿主视网膜整合。在此篇综述中,首先简要概括哺乳动物视网膜的组织结构、发育过程和调控机制,然后,重点阐述近年来科研工作者探索ES/iPS细胞体外诱导分化为视网膜细胞和组织的研究进展。

  2. Advances in gene therapy technologies to treat retinitis pigmentosa.

    Petrs-Silva, Hilda; Linden, Rafael


    Retinitis pigmentosa (RP) is a class of diseases that leads to progressive degeneration of the retina. Experimental approaches to gene therapy for the treatment of inherited retinal dystrophies have advanced in recent years, inclusive of the safe delivery of genes to the human retina. This review is focused on the development of gene therapy for RP using recombinant adenoassociated viral vectors, which show a positive safety record and have so far been successful in several clinical trials for congenital retinal disease. Gene therapy for RP is under development in a variety of animal models, and the results raise expectations of future clinical application. Nonetheless, the translation of such strategies to the bedside requires further understanding of the mutations and mechanisms that cause visual defects, as well as thorough examination of potential adverse effects.

  3. Early development of GABAergic cells of the retina in sharks: an immunohistochemical study with GABA and GAD antibodies.

    Ferreiro-Galve, Susana; Candal, Eva; Carrera, Iván; Anadón, Ramón; Rodríguez-Moldes, Isabel


    We studied the ontogeny and organization of GABAergic cells in the retina of two elasmobranches, the lesser-spotted dogfish (Scyliorhinus canicula) and the brown shyshark (Haploblepharus fuscus) by using immunohistochemistry for gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD). Both antibodies revealed the same pattern of immunoreactivity and both species showed similar organization of GABAergic cells. GABAergic cells were first detected in neural retina of embryos at stage 26, which showed a neuroepithelial appearance without any layering. In stages 27-29 the retina showed similar organization but the number of neuroblastic GABAergic cells increased. When layering became apparent in the central retina (stage-30 embryos), GABAergic cells mainly appeared organized in the outer and inner retina, and GABAergic processes and fibres were seen in the primordial inner plexiform layer (IPL), optic fibre layer and optic nerve stalk. In stage-32 embryos, layering was completed in the central retina, where immunoreactivity appeared in perikarya of the horizontal cell layer, inner nuclear layer and ganglion cell layer, and in numerous processes coursing in the IPL, optic fibre layer and optic nerve. From stage 32 to hatching (stage 34), the layered retina extends from centre-to-periphery, recapitulating that observed in the central retina at earlier stages. In adults, GABA/GAD immunoreactivity disappears from the horizontal cell layer except in the marginal retina. Our results indicate that the source of GABA in the shark retina can be explained by its synthesis by GAD. Such synthesis precedes layering and synaptogenesis, thus supporting a developmental role for GABA in addition to act as neurotransmitter and neuromodulator.

  4. SIRT1-PGC1α-NFκB Pathway of Oxidative and Inflammatory Stress during Trypanosoma cruzi Infection: Benefits of SIRT1-Targeted Therapy in Improving Heart Function in Chagas Disease

    Wen, Jian-jun; Liang, Lisa Yi


    Chronic chagasic cardiomyopathy (CCM) is presented by increased oxidative/inflammatory stress and decreased mitochondrial bioenergetics. SIRT1 senses the redox changes and integrates mitochondrial metabolism and inflammation; and SIRT1 deficiency may be a major determinant in CCM. To test this, C57BL/6 mice were infected with Trypanosoma cruzi (Tc), treated with SIRT1 agonists (resveratrol or SRT1720), and monitored during chronic phase (~150 days post-infection). Resveratrol treatment was partially beneficial in controlling the pathologic processes in Chagas disease. The 3-weeks SRT1720 therapy provided significant benefits in restoring the left ventricular (LV) function (stroke volume, cardiac output, ejection fraction etc.) in chagasic mice, though cardiac hypertrophy presented by increased thickness of the interventricular septum and LV posterior wall, increased LV mass, and disproportionate synthesis of collagens was not controlled. SRT1720 treatment preserved the myocardial SIRT1 activity and PGC1α deacetylation (active-form) that were decreased by 53% and 9-fold respectively, in chagasic mice. Yet, SIRT1/PGC1α-dependent mitochondrial biogenesis (i.e., mitochondrial DNA content, and expression of subunits of the respiratory complexes and mtDNA replication machinery) was not improved in chronically-infected/SRT1720-treated mice. Instead, SRT1720 therapy resulted in 2-10-fold inhibition of Tc-induced oxidative (H2O2 and advanced oxidation protein products), nitrosative (inducible nitric oxide synthase, 4-hydroxynonenal, 3-nitrotyrosine), and inflammatory (IFNγ, IL1β, IL6 and TNFα) stress and inflammatory infiltrate in chagasic myocardium. These benefits were delivered through SIRT1-dependent inhibition of NFκB transcriptional activity. We conclude that Tc inhibition of SIRT1/PGC1α activity was not a key mechanism in mitochondrial biogenesis defects during Chagas disease. SRT1720-dependent SIRT1 activation led to suppression of NFκB transcriptional

  5. Degenerações periféricas da retina em pacientes candidatos à cirurgia refrativa Peripheral retina degeneration in patients who are candidates for refractive surgery

    Paulo Henrique de Avila Morales


    Full Text Available Objetivo: O objetivo desse estudo é verificar em indivíduos míopes candidatos à cirurgia refrativa a prevalência dos diferentes tipos de lesões retinianas periféricas degenerativas de acordo com o tipo de miopia. Métodos: De forma prospectiva, no período de um ano, foram examinados os olhos dos pacientes no Setor de Cirurgia Refrativa do Departamento de Oftalmologia da Universidade Federal de São Paulo - Escola Paulista de Medicina que durante a sua consulta inicial apresentassem refração com equivalente esférico superior ou igual a -1,00 dioptria esférica, e não tivessem antecedentes pessoais de doença ou cirurgia ocular no período. Foi investigada a existência de lesões e/ou degenerações periféricas predisponentes ao descolamento regmatogênico de retina. Resultados: O grupo foi composto, em sua maioria, por adultos jovens (média de idade de 31 anos. Foram observados olhos com miopia baixa (263 olhos, 31%, moderada (300 olhos, 36% e alta (277 olhos, 33%; em 35,4% dos pacientes (27% dos olhos foram encontradas degenerações periféricas, sendo o branco com e sem pressão a alteração mais freqüente (23,4% dos pacientes ou 17,5% dos olhos. Entre as lesões predisponentes ao descolamento regmatogênico da retina, a mais encontrada foi a degeneração em treliça (8,6% dos pacientes ou 6% dos olhos. Conclusões: As alterações periféricas predisponentes ou não ao descolamento regmatogênico de retina apresentaram aumento de prevalência de acordo com o aumento do grau de miopia, com exceção das roturas. Todos os pacientes com miopia alta e candidatos à cirurgia refrativa devem ter a periferia retiniana de ambos os olhos examinada.Purpose: To verify, in myopic individuals who are candidates for refractive surgery, the prevalence of different types of peripheral degenerative lesions of the retina, according to the type of myopia. Methods: Prospectively, during a one-year interval, we examined the eyes of patients in

  6. Mapping the differential distribution of glycosaminoglycans in the adult human retina, choroid, and sclera

    Clark, S. J.; Keenan, T.D.; Fielder, H.L.; Collinson, L.J.; Holley, R.J.; Merry, C.L.; Kuppevelt, A.H.M.S.M. van; Day, A.J.; Bishop, P.N.


    PURPOSE. To map the distribution of different classes of glycosaminoglycans (GAGs) in the healthy human retina, choroid, and sclera. METHODS. Frozen tissue sections were made from adult human donor eyes. The GAG chains of proteoglycans (PGs) were detected with antibodies directed against various GAG

  7. Lgr5⁺ amacrine cells possess regenerative potential in the retina of adult mice.

    Chen, Mengfei; Tian, Shenghe; Glasgow, Nathan G; Gibson, Gregory; Yang, Xiaoling; Shiber, Christen E; Funderburgh, James; Watkins, Simon; Johnson, Jon W; Schuman, Joel S; Liu, Hongjun


    Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5(+) amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.

  8. Study and retina allotransplantation of porcine ciliary epithelium (CE)-derived cells

    Cogliati, Tiziana Paola


    This thesis reports the isolation, characterization and allotransplantation in porcine retina of ciliary epithelium (CE)-derived cells, also known as retinal stem cells (RSCs). The self-renewal capacity and differentiation potential of these cells in vitro and in vivo makes them candidate donors in

  9. Using myc genes to search for stem cells in the ciliary margin of the Xenopus retina.

    Xue, Xiao Yan; Harris, William A


    The ciliary marginal zone (CMZ) of fish and frog retinas contains cells that proliferate throughout postembryonic development as the retina grows with increasing body size, indicating the presence of stem cells in this region. However, neither the location nor the molecular identity of retinal stem cells has been identified. Here, we show in Xenopus that c-myc and n-myc are sequentially expressed both during development and in the post-embryonic retina. The c-myc+/n-myc- cells near the extreme periphery of the CMZ cycle more slowly and preferentially retain DNA label compared to their more central cmyc+/n-myc+ neighbors which cycle rapidly and preferentially dilute DNA label. During retinal development c-myc is functionally required earlier than n-myc, and n-myc expression depends on earlier c-myc expression. The expression of c-myc but not n-myc in the CMZ depends on growth factor signaling. Our results suggest that c-myc+/n-myc- cells in the far peripheral CMZ are candidates for a niche-dependent population of retinal stem cells that give rise to more centrally located and rapidly dividing n-myc+ progenitors of more limited proliferative potential. Analysis of homologues of these genes in the zebrafish CMZ suggests that the transition from c-myc to n-myc expression might be conserved in other lower vertebrates whose retinas growth throughout life.

  10. An analog VLSI chip emulating sustained and transient response channels of the vertebrate retina.

    Kameda, S; Yagi, T


    A silicon retina that emulates the sustained and the transient responses in the vertebrate retina was fabricated. The circuit of the chip consists of two layers of resistive network that have different length constants. The output emulating the sustained response possesses a Laplacian-Gaussian-like receptive field and, therefore, carries out a smoothing and contrast-enhancement on the input images. This receptive field was realized by subtracting voltages distributing over the two resistive networks. The output emulating the transient response was obtained by subtracting consecutive images that were smoothed out by the resistive network and is sensitive to moving objects. The outputs of these two channels can be obtained alternately from the silicon retina in real time, within time delays not exceeding a few tens of milliseconds, with indoor illumination. The outputs of the chip are offset-suppressed analog voltages since the uncontrollable mismatches of transistor characteristics are compensated for with the aid of sample/hold circuits embedded in each pixel circuit. The silicon retina fabricated in the present study can be readily used in current engineering applications, e.g., robot vision.

  11. Foveal reflection analyzer : on the spectral and directional reflectance of the retina

    Zagers, Niels Petrus Antonius


    The first part of this thesis was on the development of a new instrument for measurement of light reflected from the retina in a living human eye. The key element is an imaging spectrograph, with its slit placed conjugate to the pupil of the eye. The instrument measures both the spectral and the dir

  12. Celsr3 is required for normal development of GABA circuits in the inner retina.

    Alaron Lewis


    Full Text Available The identity of the specific molecules required for the process of retinal circuitry formation is largely unknown. Here we report a newly identified zebrafish mutant in which the absence of the atypical cadherin, Celsr3, leads to a specific defect in the development of GABAergic signaling in the inner retina. This mutant lacks an optokinetic response (OKR, the ability to visually track rotating illuminated stripes, and develops a super-normal b-wave in the electroretinogram (ERG. We find that celsr3 mRNA is abundant in the amacrine and ganglion cells of the retina, however its loss does not affect synaptic lamination within the inner plexiform layer (IPL or amacrine cell number. We localize the ERG defect pharmacologically to a late-stage disruption in GABAergic modulation of ON-bipolar cell pathway and find that the DNQX-sensitive fast b1 component of the ERG is specifically affected in this mutant. Consistently, we find an increase in GABA receptors on mutant ON-bipolar terminals, providing a direct link between the observed physiological changes and alterations in GABA signaling components. Finally, using blastula transplantation, we show that the lack of an OKR is due, at least partially, to Celsr3-mediated defects within the brain. These findings support the previously postulated inner retina origin for the b1 component and reveal a new role for Celsr3 in the normal development of ON visual pathway circuitry in the inner retina.

  13. Expression of Endoplasmic Reticulum Stress-Related Factors in the Retinas of Diabetic Rats

    Shu Yan


    Full Text Available Recent reports show that ER stress plays an important role in diabetic retinopathy (DR, but ER stress is a complicated process involving a network of signaling pathways and hundreds of factors, What factors involved in DR are not yet understood. We selected 89 ER stress factors from more than 200, A rat diabetes model was established by intraperitoneal injection of streptozotocin (STZ. The expression of 89 ER stress-related factors was found in the retinas of diabetic rats, at both 1- and 3-months after development of diabetes, by quantitative real-time polymerase chain reaction arrays. There were significant changes in expression levels of 13 and 12 ER stress-related factors in the diabetic rat retinas in the first and third month after the development of diabetes, Based on the array results, homocysteine- inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1(HERP, and synoviolin(HRD1 were studied further by immunofluorescence and Western blot. Immunofluorescence and Western blot analyses showed that the expression of HERP was reduced in the retinas of diabetic rats in first and third month. The expression of Hrd1 did not change significantly in the retinas of diabetic rats in the first month but was reduced in the third month.

  14. Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study

    P Aggarwal; T C Nag; S Wadhwa


    During normal ageing, the rods (and other neurones) undergo a significant decrease in density in the human retina from the fourth decade of life onward. Since the rods synapse with the rod bipolar cells in the outer plexiform layer, a decline in rod density (mainly due to death) may ultimately cause an associated decline of the neurones which, like the rod bipolar cells, are connected to them. The rod bipolar cells are selectively stained with antibodies to protein kinase C-. This study examined if rod bipolar cell density changes with ageing of the retina, utilizing donor human eyes (age: 6–91 years). The retinas were fixed and their temporal parts from the macula to the mid-periphery sectioned and processed for protein kinase C- immunohistochemistry. The density of the immunopositive rod bipolar cells was estimated in the mid-peripheral retina (eccentricity: 3–5 mm) along the horizontal temporal axis. The results show that while there is little change in the density of the rod bipolar cells from 6 to 35 years (2.2%), the decline during the period from 35 to 62 years is about 21% and between seventh and tenth decades, it is approximately 27%.

  15. Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics

    Schallek, Jesse; Li, Hongbin; Kardon, Randy; Kwon, Young; Abramoff, Michael


    purpose. To characterize the properties of stimulus-evoked retinal intrinsic signals and determine the underlying origins. methods. Seven adult cats were anesthetized and paralyzed to maximize imaging stability. The retina was stimulated with a liquid crystal display (LCD) integrated into a modifi

  16. [Functional alterations in the retina following a 10 Gy gamma irradiation localized in the eye].

    Bagot, J D; Courant, D; Court, L


    A single-eye irradiation of 10 Gy (0.8 Gy. min-1) induces impairments of the electrical responses of the rabbit retina in dark adaptation. These are associated with reversible alteration of the photoreceptors and the preganglionic neurons and a disturbance of all the mechanisms of adaptation. Possible relationships between these functional alterations and the effects of irradiation are discussed.

  17. Melatonin reprogrammes proteomic profile in light-exposed retina in vivo

    Zhang, Ruonan; Hrushesky, William J.M.; Wood, Patricia A.; Lee, Sung Haeng; Hunt, Richard C.; Jahng, Wan Jin


    Melatonin, a small organic molecule synthesized by the pineal gland and the retina, has a variety of physiologic functions such as circadian clock pacemaker and antioxidant. Retinal melatonin is down-regulated by light and is barely detectable during the day. The absence of melatonin in the retina during prolonged light exposure may contribute to light-induced retinal degeneration. We sought to investigate the impact of melatonin in the light-exposed retina using proteomic approaches. We exposed mice to either light (250–300 lux) for 12 h followed by 12 h of darkness or the same intensity of continuous light for 7 days. In half of the animals exposed to continuous light, melatonin was injected each night. Proteomic analysis of the retina from these three groups of animals showed that five proteins prominently up-regulated by constant light were down-regulated by melatonin treatment. These five proteins were identified as vimentin, serine/threonine-protein phosphatase 2A, Rab GDP dissociation inhibitor alpha, guanine nucleotide-binding protein Go alpha, and retinaldehyde-binding protein. These five proteins are known to be involved in several cellular processes that may contribute to light-induced retinal degeneration. Identification of melatonin target proteins in our study provides a basis for future studies on melatonin’s potential in preventing or treating light-induced retinal degeneration. PMID:20434483

  18. Retinal Physiology: Non-Bipolar-Cell Excitatory Drive in the Inner Retina.

    Baden, Tom; Euler, Thomas


    The long-held view that bipolar cells provide the exclusive excitatory drive to the mammalian inner retina has been challenged: new studies indicate that, instead, at least two cells that lack the dendrites characteristic for bipolar cells, and therefore resemble amacrine cells, excite inner retinal circuits using glutamate.

  19. Quantitative analysis of retina layer elasticity based on automatic 3D segmentation (Conference Presentation)

    He, Youmin; Qu, Yueqiao; Zhang, Yi; Ma, Teng; Zhu, Jiang; Miao, Yusi; Humayun, Mark; Zhou, Qifa; Chen, Zhongping


    Age-related macular degeneration (AMD) is an eye condition that is considered to be one of the leading causes of blindness among people over 50. Recent studies suggest that the mechanical properties in retina layers are affected during the early onset of disease. Therefore, it is necessary to identify such changes in the individual layers of the retina so as to provide useful information for disease diagnosis. In this study, we propose using an acoustic radiation force optical coherence elastography (ARF-OCE) system to dynamically excite the porcine retina and detect the vibrational displacement with phase resolved Doppler optical coherence tomography. Due to the vibrational mechanism of the tissue response, the image quality is compromised during elastogram acquisition. In order to properly analyze the images, all signals, including the trigger and control signals for excitation, as well as detection and scanning signals, are synchronized within the OCE software and are kept consistent between frames, making it possible for easy phase unwrapping and elasticity analysis. In addition, a combination of segmentation algorithms is used to accommodate the compromised image quality. An automatic 3D segmentation method has been developed to isolate and measure the relative elasticity of every individual retinal layer. Two different segmentation schemes based on random walker and dynamic programming are implemented. The algorithm has been validated using a 3D region of the porcine retina, where individual layers have been isolated and analyzed using statistical methods. The errors compared to manual segmentation will be calculated.

  20. Foveal reflection analyzer : on the spectral and directional reflectance of the retina

    Zagers, Niels Petrus Antonius


    The first part of this thesis was on the development of a new instrument for measurement of light reflected from the retina in a living human eye. The key element is an imaging spectrograph, with its slit placed conjugate to the pupil of the eye. The instrument measures both the spectral and the

  1. Expression of neuropeptides and their receptors in the developing retina of mammals

    bagnoli, P; M. Dal Monte; Casini, G.


    The present review examines various aspects of the developmental expression of neuropeptides and of their receptors in mammalian retinas, emphasizing their possible roles in retinal maturation. Different peptidergic systems have been investigated with some detail during retinal development, including substance P (SP), somatostatin (SRIF), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y (NPY...

  2. Species-specific wiring for direction selectivity in the mammalian retina.

    Ding, Huayu; Smith, Robert G; Poleg-Polsky, Alon; Diamond, Jeffrey S; Briggman, Kevin L


    Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse distributions along SAC dendrites: input and output synapses are segregated, with inputs restricted to proximal dendrites; and the distribution of inhibitory inputs is fundamentally different from that observed in rabbit retina. An anatomically constrained SAC network model suggests that SAC–SAC wiring differences between mouse and rabbit retina underlie distinct contributions of synaptic inhibition to velocity and contrast tuning and receptive field structure. In particular, the model indicates that mouse connectivity enables SACs to encode lower linear velocities that account for smaller eye diameter, thereby conserving angular velocity tuning. These predictions are confirmed with calcium imaging of mouse SAC dendrites responding to directional stimuli.

  3. Investigation of alterations in multifractality in optical coherence tomographic images of in vivo human retina

    Das, Nandan Kumar; Mukhopadhyay, Sabyasachi; Ghosh, Nirmalya; Chhablani, Jay; Richhariya, Ashutosh; Divakar Rao, Kompalli; Sahoo, Naba Kishore


    Optical coherence tomography (OCT) enables us to monitor alterations in the thickness of the retinal layer as disease progresses in the human retina. However, subtle morphological changes in the retinal layers due to early disease progression often may not lead to detectable alterations in the thickness. OCT images encode depth-dependent backscattered intensity distribution arising due to the depth distributions of the refractive index from tissue microstructures. Here, such depth-resolved refractive index variations of different retinal layers were analyzed using multifractal detrended fluctuation analysis, a special class of multiresolution analysis tools. The analysis extracted and quantified microstructural multifractal information encoded in normal as well as diseased human retinal OCT images acquired in vivo. Interestingly, different layers of the retina exhibited different degrees of multifractality in a particular retina, and the individual layers displayed consistent multifractal trends in healthy retinas of different human subjects. In the retinal layers of diabetic macular edema (DME) subjects, the change in multifractality manifested prominently near the boundary of the DME as compared to the normal retinal layers. The demonstrated ability to quantify depth-resolved information on multifractality encoded in OCT images appears promising for the early diagnosis of diseases of the human eye, which may also prove useful for detecting other types of tissue abnormalities from OCT images.

  4. Expression of ciliary neurotrophic factor after induction of ocular hypertension in the retina of rats

    WU Qiang; ZHANG Min; SONG Bei-wen; LU Bin; HU Ping


    Background Glaucoma is mainly characterized by the loss of retinal ganglion cells. Ciliary neurotrophic factor (CNTF) is believed to stimulate the regeneration of axons of retinal ganglion cells. The objective of our study was to detect the expression of CNTF in the retina of a rat glaucoma model with increased intraocular pressure (lOP).Methods The rat glaucoma model was set up by electrocoagulating at least three episcleral and limbal veins. The location and the expression level of CNTF were detected at 1, 3, 7, 14, and 28 days post-surgery by immunohistochemistry, semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), and Western blot analysis.Results The rat glaucoma model with chronic, moderately elevated lOP was successfully produced. A minimum expression of CNTF was found in the ganglion cell layer of the retinas of the control group, and temporally increased expression and intensity of CNTF were found in the experimental retinas.Conclusion The expression of endogenous CNTF in the rat retina was found altered after the induction of ocular hypertension.

  5. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species

    Barbara Amann


    Full Text Available Aquaporins (AQPs are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11.

  6. The Wilms' tumor gene Wt1 is required for normal development of the retina.

    Wagner, Kay-Dietrich; Wagner, Nicole; Vidal, Valerie P I; Schley, Gunnar; Wilhelm, Dagmar; Schedl, Andreas; Englert, Christoph; Scholz, Holger


    The Wilms' tumor gene Wt1 is known for its important functions during genitourinary and mesothelial formation. Here we show that Wt1 is necessary for neuronal development in the vertebrate retina. Mouse embryos with targeted disruption of Wt1 exhibit remarkably thinner retinas than age-matched wild-type animals. A large fraction of retinal ganglion cells is lost by apoptosis, and the growth of optic nerve fibers is severely disturbed. Strikingly, expression of the class IV POU-domain transcription factor Pou4f2 (formerly Brn-3b), which is critical for the survival of most retinal ganglion cells, is lost in Wt1(-/-) retinas. Forced expression of Wt1 in cultured cells causes an up-regulation of Pou4f2 mRNA. Moreover, the Wt1(-KTS) splice variant can activate a reporter construct carrying 5'-regulatory sequences of the human POU4F2. The lack of Pou4f2 and the ocular defects in Wt1(-/-) embryos are rescued by transgenic expression of a 280 kb yeast artificial chromosome carrying the human WT1 gene. Taken together, our findings demonstrate a continuous requirement for Wt1 in normal retina formation with a critical role in Pou4f2-dependent ganglion cell differentiation.

  7. A preparation for studying electrical stimulation of the retina in vivo in rat.

    Baig-Silva, M S; Hathcock, C D; Hetling, J R


    A remaining challenge to the development of electronic prostheses for vision is improving the effectiveness of retinal stimulation. Electrode design and stimulus parameters need to be optimized such that the neural output from the retina conveys information to the mind's eye that aids the patient in interpreting his or her environment. This optimization will require a detailed understanding of the response of the retina to electrical stimulation. The identity and response characteristics of the cellular targets of stimulation need to be defined and evaluated. Described here is an in vivo preparation for studying electrical stimulation of the retina in rat at the cellular level. The use of rat makes available a number of well-described models of retinal disease that motivate prosthesis development. Artificial stimulation can be investigated by adapting techniques traditionally employed to study the response of the retina to photic stimuli, such as recording at the cornea, single-cell recording, and pharmacological dissection of the response. Pilot studies include amplitude-intensity response data for subretinal and transretinal stimulation paradigms recorded in wild-type rats and a transgenic rat model of autosomal dominant retinitis pigmentosa. The ability to record single-unit ganglion cell activity in vivo is also demonstrated.

  8. Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat

    Rath, Martin F; Morin, Fabrice; Shi, Qiong


    Otx2 and Crx are vertebrate orthologs of the orthodenticle family of homeobox genes, which are involved in retinal development. In this study, the temporal expression patterns of Otx2 and Crx in the rat retina during embryonic and postnatal stages of development were analyzed in detail. This conf...

  9. Photopic spectral sensitivities of the red and the yellow field of the pigeon retina

    Wortel, J.F.; Wubbels, R.J.; Nuboer, J.F.W.


    The spectral sensitivities of the red field and the yellow field in the retina of the homing pigeon (Columba Livia) were determined on the basis of ERG responses. Between 450 and 550 nm the relative spectral sensitivity of the yellow field turned out to be higher than that of the red field. The resu

  10. Adaptive Colour Contrast Coding in the Salamander Retina Efficiently Matches Natural Scene Statistics

    Vasserman, Genadiy; Schneidman, Elad; Segev, Ronen


    The visual system continually adjusts its sensitivity to the statistical properties of the environment through an adaptation process that starts in the retina. Colour perception and processing is commonly thought to occur mainly in high visual areas, and indeed most evidence for chromatic colour contrast adaptation comes from cortical studies. We show that colour contrast adaptation starts in the retina where ganglion cells adjust their responses to the spectral properties of the environment. We demonstrate that the ganglion cells match their responses to red-blue stimulus combinations according to the relative contrast of each of the input channels by rotating their functional response properties in colour space. Using measurements of the chromatic statistics of natural environments, we show that the retina balances inputs from the two (red and blue) stimulated colour channels, as would be expected from theoretical optimal behaviour. Our results suggest that colour is encoded in the retina based on the efficient processing of spectral information that matches spectral combinations in natural scenes on the colour processing level. PMID:24205373

  11. Simulated human eye retina adaptive optics imaging system based on a liquid crystal on silicon device

    Jiang Bao-Guang; Cao Zhao-Liang; Mu Quan-Quan; Hu Li-Fa; Li Chao; Xuan Li


    In order to obtain a clear image of the retina of model eye, an adaptive optics system used to correct the wave-front error is introduced in this paper. The spatial light modulator that we use here is a liquid crystal on a silicon device instead of a conversional deformable mirror. A paper with carbon granule is used to simulate the retina of human eye. The pupil size of the model eye is adjustable (3-7 mm). A Shack-Hartman wave-front sensor is used to detect the wave-front aberration. With this construction, a value of peak-to-valley is achieved to be 0.086 λ, where A is wavelength.The modulation transfer functions before and after corrections are compared. And the resolution of this system after correction (691p/m) is very close to the diffraction limit resolution. The carbon granule on the white paper which has a size of 4.7μm is seen clearly. The size of the retina cell is between 4 and 10 μm. So this system has an ability to image the human eye's retina.

  12. In vivo imaging of raptor retina with ultra high resolution spectral domain optical coherence tomography

    Ruggeri, Marco; Major, James C., Jr.; McKeown, Craig; Wehbe, Hassan; Jiao, Shuliang; Puliafito, Carmen A.


    Among birds, raptors are well known for their exceptional eyesight, which is partly due to the unique structure of their retina. Because the raptor retina is the most advanced of any animal species, in vivo examination of its structure would be remarkable. Furthermore, a noticeable percentage of traumatic ocular injuries are identified in birds of prey presented to rehabilitation facilities. Injuries affecting the posterior segment have been considered as a major impact on raptor vision. Hence, in vivo examination of the structure of the posterior segment of the raptors would be helpful for the diagnosis of traumatized birds. The purpose of this study is to demonstrate the application of ultrahigh-resolution Spectral Domain Optical Coherence Tomography (SD-OCT) for non contact in vivo imaging of the retina of birds of prey, which to the best of our knowledge has never been attempted. For the first time we present high quality OCT images of the retina of two species of bird of prey, one diurnal hawk and one nocturnal owl.

  13. Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain.

    Bouchard, Jean-François; Casanova, Christian; Cécyre, Bruno; Redmond, William John


    Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.

  14. Adaptive colour contrast coding in the salamander retina efficiently matches natural scene statistics.

    Genadiy Vasserman

    Full Text Available The visual system continually adjusts its sensitivity to the statistical properties of the environment through an adaptation process that starts in the retina. Colour perception and processing is commonly thought to occur mainly in high visual areas, and indeed most evidence for chromatic colour contrast adaptation comes from cortical studies. We show that colour contrast adaptation starts in the retina where ganglion cells adjust their responses to the spectral properties of the environment. We demonstrate that the ganglion cells match their responses to red-blue stimulus combinations according to the relative contrast of each of the input channels by rotating their functional response properties in colour space. Using measurements of the chromatic statistics of natural environments, we show that the retina balances inputs from the two (red and blue stimulated colour channels, as would be expected from theoretical optimal behaviour. Our results suggest that colour is encoded in the retina based on the efficient processing of spectral information that matches spectral combinations in natural scenes on the colour processing level.

  15. Progesterone receptor membrane component 1 (PGRMC1) expression in murine retina

    Shanmugam, Arul K.; Mysona, Barbara A.; Wang, Jing; Zhao, Jing; Tawfik, Amany; Sanders, A.; Markand, Shanu; Zorrilla, Eric; Ganapathy, Vadivel; Bollinger, Kathryn E.; Smith, Sylvia B.


    Purpose Sigma receptor 1 (σR1) and 2 (σR2) are thought to be two distinct proteins which share the ability to bind multiple ligands, several of which are common to both receptors. Whether σR1 and σR2 share overlapping biological functions is unknown. Recently, progesterone receptor membrane component 1 (PGRMC1) was shown to contain the putative σR2 binding site. PGRMC1 has not been studied in retina. We hypothesize that biological interactions between σR1 and PGRMC1 will be evidenced by compensatory upregulation of PGRMC1 in σR1−/− mice. Methods Immunofluorescence, RT-PCR, and immunoblotting methods were used to analyze expression of PGRMC1 in wild type mouse retina. Tissues from σR1−/− mice were used to investigate whether a biological interaction exists between σR1 and PGRMC1. Results In the eye, PGRMC1 is expressed in corneal epithelium, lens, ciliary body epithelium, and retina. In retina, PGRMC1 is present in Müller cells and retinal pigment epithelium. This expression pattern is similar, but not identical to σR1. PGRMC1 protein levels in neural retina and eye cup from σR1−/− mice did not differ from wild type mice. Nonocular tissues, lung, heart, and kidney showed similar Pgrmc1 gene expression in wild type and σR1−/− mice. In contrast, liver, brain and intestine showed increased Pgrmc1 gene expression in σR1−/− mice. Conclusion Despite potential biological overlap, deletion of σR1 did not result in a compensatory change in PGRMC1 protein levels in σR1−/− mouse retina. Increased Pgrmc1 gene expression in organs with high lipid content such as liver, brain, and intestine indicate a possible tissue specific interaction between σR1 and PGRMC1. The current studies establish the presence of PGRMC1 in retina and lay the foundation for analysis of its biological function. PMID:26642738


    ZHONG Yi-sheng; LIU Xiao-hong; HUANG Ping; CHENG Yu


    Objective To investigate the distribution of erythropoietin (EPO) and erythropoietin receptor (EPOR) expression in the postnatal rat retina development.Methods Forty-two male Sprague-Dawley rats were divided into 7 groups according to their various postnatal days: postnatal 1 d (D1 group), 3 d (D3 group), 1 week (W1 group), 2 weeks (W2 group), 3 weeks (W3 group), 4 weeks (W4 group) and 8 weeks (W8 group) (n=6). Single eye was randomly chosen from each rat for the study. The retinal sections were stained with hematoxylin and eosin (HE) and used for the retina development observation. Immunohistochemical staining was used to localize EPO and EPOR expressions in retinas of different stages of development, and the expression intensities were determined by an image plus 4 program.Results The retinal inner nuclear layer (INL) and outer nuclear layer (ONL) were mixed together and had not yet fully differentiated in D1 and D3 groups. The INL and ONL formed their own independent regions and the outer plexiform layer (OPL) appeared between two layers in W1 group. With the postnatal retinal development, the inner plexiform layer (IPL), rods and cones layer (RCL), and OPL were gradually widened and stabilized in W2 to W3 groups. EPO/EPOR expressions located prominently in the inner part of the postnatal rat developing retinas. The expression of EPO in GCL and INL gradually increased from D1 to W4, then the expression decreased in W8. Expression of EPOR in GCL gradually increased from D1 to W1, then decreased in W2; and it gradually increased again from W3 to W8. Expression of EPOR in INL gradually increased from D1 to W1, then decreased in W2; and it continued to decrease from W3 to W8. Expression of EPOR in the external segment of RCL gradually increased from D1 to W8. However, expression in the internal segment of RCL gradually decreased from D1 to W3, then no obvious expression was seen in the internal segment of RCL in W4 and W8.Conclusion EPO/EPOR expressions locate

  17. Spatiotemporal pattern of doublecortin expression in the retina of the sea lamprey

    Blanca eFernández-López


    Full Text Available Despite the importance of doublecortin (DCX for the development of the nervous system, its expression in the retina of most vertebrates is still unknown. The key phylogenetic position of lampreys, together with their complex life cycle, with a long blind larval stage and an active predator adult stage, makes them an interesting model to study retinal development. Here, we studied the spatiotemporal pattern of expression of DCX in the retina of the sea lamprey. In order to characterize the DCX expressing structures, the expression of acetylated α-tubulin (a neuronal marker and cytokeratins (glial marker was also analyzed. Tract-tracing methods were used to label ganglion cells. DCX immunoreactivity appeared initially in photoreceptors, ganglion cells and in fibers of the prolarval retina. In larvae smaller than 100 mm, DCX expression was observed in photoreceptors, in cells located in the inner nuclear and inner plexiform layers and in fibers coursing in the nuclear and inner plexiform layers, and in the optic nerve. In retinas of premetamorphic and metamorphic larvae, DCX immunoreactivity was also observed in radially oriented cells and fibers and in a layer of cells located in the outer part of the inner neuroblastic layer of the lateral retina. Photoreceptors and fibers ending in the outer limitans membrane showed DCX expression in adults. Some retinal pigment epithelium cells were also DCX immunoreactive. Immunofluorescence for α-tubulin in premetamorphic larvae showed coexpression in most of the DCX immunoreactive structures. No cells/fibers were found showing DCX and cytokeratins colocalization. The perikaryon of mature ganglion cells is DCX negative. The expression of DCX in sea lamprey retinas suggests that it could play roles in the migration of cells that differentiate in the metamorphosis, in the establishment of connections of ganglion cells and in the development of photoreceptors. Our results also suggest that the radial glia and

  18. Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina.

    Park, Hae-Young Lopilly; Kim, Jie Hyun; Sun Kim, Hwa; Park, Chan Kee


    As an alternative to a viral vector, the application of stem cells to transfer specific genes is under investigation in various organs. Using this strategy may provide more effective method to supply neurotrophic factor to the neurodegenerative diseases caused by neurotrophic factor deprivation. This study investigated the possibility and efficacy of stem cell-based delivery of the brain-derived neurotrophic factor (BDNF) gene to rat retina. Rat BDNF cDNA was transduced into rat bone marrow mesenchymal stem cells (rMSCs) using a retroviral vector. Its incorporation into the experimental rat retina and the expression of BDNF after intravitreal injection or subretinal injection were detected by real-time PCR, western blot analysis, and immunohistochemical staining. For the incorporated rMSCs, retinal-specific marker staining was performed to investigate the changes in morphology and the characteristics of the stem cells. Transduction of the rMSCs by retrovirus was effective, and the transduced rMSCs expressed high levels of the BDNF gene and protein. The subretinal injection of rMSCs produced rMSC migration and incorporation into the rat retina (about 15.7% incorporation rate), and retinal BDNF mRNA and protein expression was increased at 4 weeks after transplantation. When subretinal injection of rMSCs was applied to axotomized rat retina, it significantly increased the expression of BDNF until 4 weeks after transplantation. Some of the transplanted rMSCs exhibited morphological changes, but the retinal-specific marker stain was not sufficient to indicate whether neuronal differentiation had occurred. Using mesenchymal stem cells to deliver the BDNF gene to the retina may provide new treatment for glaucoma.

  19. Post-translational processing of synaptophysin in the rat retina is disrupted by diabetes.

    Travis S D'Cruz

    Full Text Available Synaptophysin, is an abundant presynaptic protein involved in synaptic vesicle recycling and neurotransmitter release. Previous work shows that its content is significantly reduced in the rat retina by streptozotocin (STZ-diabetes. This study tested the hypothesis that STZ-diabetes alters synaptophysin protein turnover and glycosylation in the rat retina. Whole explant retinas from male Sprague-Dawley rats were used in this study. Rats were made diabetic by a single intraperitoneal STZ injection (65 mg/kg body weight in 10 mM sodium citrate, pH 4.5. mRNA translation was measured using a (35S-methionine labeling assay followed by synaptophysin immunoprecipitation and autoradiography. A pulse-chase study was used to determine the depletion of newly synthesized synaptophysin. Depletion of total synaptophysin was determined after treatment with cycloheximide. Mannose rich N-glycosylated synaptophysin was detected by treating retinal lysates with endoglycosidase H followed by immunoblot analysis. Synaptophysin mRNA translation was significantly increased after 1 month (p<0.001 and 2 months (p<0.05 of STZ-diabetes, compared to age-matched controls. Newly synthesized synaptophysin degradation was significantly accelerated in the retina after 1 and 2 months of diabetes compared to controls (p<0.05. Mannose rich glycosylated synaptophysin was significantly increased after 1 month of STZ-diabetes compared to controls (p<0.05.These data suggest that diabetes increases mRNA translation of synaptophysin in the retina, resulting in an accumulation of mannose rich glycosylated synaptophysin, a transient post-translational state of the protein. This diabetes-induced irregularity in post-translational processing could explain the accelerated degradation of retinal synaptophysin in diabetes.

  20. Alzheimer's Disease-Related Protein Expression in the Retina of Octodon degus.

    Lucia Y Du

    Full Text Available New studies show that the retina also undergoes pathological changes during the development of Alzheimer's disease (AD. While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with Aβ aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. Aβ4G8 and Aβ6E10 detected Aβ peptides in some of the young animals but the expression was higher in the adults. Aβ peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL and ganglion cell layer (GCL. Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected Aβ oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that Aβ peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye.

  1. Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus

    Du, Lucia Y.; Chang, Lily Y-L.; Ardiles, Alvaro O.; Tapia-Rojas, Cheril; Araya, Joaquin; Inestrosa, Nibaldo C.


    New studies show that the retina also undergoes pathological changes during the development of Alzheimer’s disease (AD). While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with Aβ aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. Aβ4G8 and Aβ6E10 detected Aβ peptides in some of the young animals but the expression was higher in the adults. Aβ peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL) and ganglion cell layer (GCL). Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected Aβ oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months) animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that Aβ peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye. PMID:26267479

  2. Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.

    Francis Béby

    Full Text Available BACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE, a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE.

  3. Circadian organization of the mammalian retina: from gene regulation to physiology and diseases.

    McMahon, Douglas G; Iuvone, P Michael; Tosini, Gianluca


    The retinal circadian system represents a unique structure. It contains a complete circadian system and thus the retina represents an ideal model to study fundamental questions of how neural circadian systems are organized and what signaling pathways are used to maintain synchrony of the different structures in the system. In addition, several studies have shown that multiple sites within the retina are capable of generating circadian oscillations. The strength of circadian clock gene expression and the emphasis of rhythmic expression are divergent across vertebrate retinas, with photoreceptors as the primary locus of rhythm generation in amphibians, while in mammals clock activity is most robust in the inner nuclear layer. Melatonin and dopamine serve as signaling molecules to entrain circadian rhythms in the retina and also in other ocular structures. Recent studies have also suggested GABA as an important component of the system that regulates retinal circadian rhythms. These transmitter-driven influences on clock molecules apparently reinforce the autonomous transcription-translation cycling of clock genes. The molecular organization of the retinal clock is similar to what has been reported for the SCN although inter-neural communication among retinal neurons that form the circadian network is apparently weaker than those present in the SCN, and it is more sensitive to genetic disruption than the central brain clock. The melatonin-dopamine system is the signaling pathway that allows the retinal circadian clock to reconfigure retinal circuits to enhance light-adapted cone-mediated visual function during the day and dark-adapted rod-mediated visual signaling at night. Additionally, the retinal circadian clock also controls circadian rhythms in disk shedding and phagocytosis, and possibly intraocular pressure. Emerging experimental data also indicate that circadian clock is also implicated in the pathogenesis of eye disease and compelling experimental data

  4. Step-by-step instructions for retina recordings with perforated multi electrode arrays.

    Katja Reinhard

    Full Text Available Multi-electrode arrays are a state-of-the-art tool in electrophysiology, also in retina research. The output cells of the retina, the retinal ganglion cells, form a monolayer in many species and are well accessible due to their proximity to the inner retinal surface. This structure has allowed the use of multi-electrode arrays for high-throughput, parallel recordings of retinal responses to presented visual stimuli, and has led to significant new insights into retinal organization and function. However, using conventional arrays where electrodes are embedded into a glass or ceramic plate can be associated with three main problems: (1 low signal-to-noise ratio due to poor contact between electrodes and tissue, especially in the case of strongly curved retinas from small animals, e.g. rodents; (2 insufficient oxygen and nutrient supply to cells located on the bottom of the recording chamber; and (3 displacement of the tissue during recordings. Perforated multi-electrode arrays (pMEAs have been found to alleviate all three issues in brain slice recordings. Over the last years, we have been using such perforated arrays to study light evoked activity in the retinas of various species including mouse, pig, and human. In this article, we provide detailed step-by-step instructions for the use of perforated MEAs to record visual responses from the retina, including spike recordings from retinal ganglion cells and in vitro electroretinograms (ERG. In addition, we provide in-depth technical and methodological troubleshooting information, and show example recordings of good quality as well as examples for the various problems which might be encountered. While our description is based on the specific equipment we use in our own lab, it may also prove useful when establishing retinal MEA recordings with other equipment.

  5. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress.

    Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena; Garelli, Andrés; Politi, Luis E; Agbaga, Martin-Paul; Anderson, Robert E; Rotstein, Nora P


    Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA.

  6. Expression patterns of the retinal development-related genes in the fetal and adult retina

    LI Hui-ming; WANG Feng; QIU Wei; LIU Yan; HUANG Qian


    Background Retina is important in converting light into neural signals, but little is known about the regulatory genes essential for the retinal morphological formation, development and functional differentiation. This study aimed to investigate the mRNA expression patterns and cellular or subcellular distribution of 33 differentially expressed genes in the retina belonging to the early and middle-late embryogenesis stages as well as the early adult stage during human development.Methods In situ hybridization and real-time fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) were used to assay 33 differentially expressed genes which were screened out using microarray analysis and were not present in the retinal cDNA or the Expressed Sequence Tags (EST) database of the National Eye Institute (NEI) Genebank.Results Nine of the 33 genes belonged to EST or the unknown cDNA fragments, and the remaining belonged to the novel genes in the retina. During the human retinal development 17 genes were down-regulated, 6 were up-regulated and the remaining 10 were relatively unchanged. Most of the genes expressed in all layers of the retina at the gestation stage, and in the fully developed retina some genes examined did show higher expression level in certain specific cells and structures such as retinal ganglion cells or the outer segment of photoreceptor cells.Conclusion The gene expression profile during retinal development possesses temporal and spatial distribution features, which can provide experimental evidence for further research of the functions of those genes.

  7. Therapeutic effect of bFGF on retina ischemia-reperfusion injury

    牛膺筠; 赵岩松; 高云霞; 周占宇; 王红云; 袁春燕


    Background Basic fibroblast growth factor (bFGF) plays important roles in retina degeneration, light injury, mechanical injury, especially in retina ischemia-reperfusion injury (RIRI). This study was to investigate the therapeutical effect of bFGF on RIRI and its mechanisms. Methods Experimental RIRI was induced by increasing intraocular pressure (lOP) in the eyes of 48 rats. These rats were divided into normal control, ischemia-reperfusion and bFGF-treated groups. Histological and ultrastructural changes of in the retina of different groups were observed, and the number of retinal ganglion cells (RGCs) was quantitatively analyzed under microscopy. Apoptotic cells were detected using the TdT-dUTP terminal nick-end labeling (TUNEL) method. The expression of caspase-3 was determined by streptavidin peroxidase (SP) immunohistochemistry. Atomic absorption spectrum method was used to evaluate the intracellular calcium changes. Results At the early stage of retinal ischemia-reperfusion injury, retina edema in the treated group was significantly eliminated compared with the untreated ischemic animals. RGCs in the bFGF-treated group was more than those in the untreated ischemic group during the post-reperfusion stages. In ischemic group, apoptotic cells could be found at 6th hours after reperfusion and reached the peak at 24th hours. At 72th hours no apoptotic cells could be found. The changes in caspase-3 expression had a similar manner. The intracellular calcium of rat retina began to increase at l th hour, reached the peak at 24 hours, and began to decease at 72th hours. The change of the three markers in the treatment group showed a similar pattern, but they were all relatively less obvious. Conclusion Apoptosis may play a vital role in RIRI. bFGF may has therapeutical effects on RIRI by inhibiting the increase of intracellular calciums and caspase-3 expression.

  8. Evolutionary loss of cone photoreception in balaenid whales reveals circuit stability in the mammalian retina.

    Schweikert, Lorian E; Fasick, Jeffry I; Grace, Michael S


    The classical understanding of mammalian vision is that it occurs through "duplex" retinae containing both rod and cone photoreceptors, the signals from which are processed through rod- and/or cone-specific signaling pathways. The recent discovery of rod monochromacy in some cetacean lineages provides a novel opportunity to investigate the effects of an evolutionary loss of cone photoreception on retinal organization. Sequence analysis of right whale (Eubalaena glacialis; family Balaenidae) cDNA derived from long-wavelength sensitive (LWS) cone opsin mRNA identified several mutations in the opsin coding sequence, suggesting the loss of cone cell function, but maintenance of non-photosensitive, cone opsin mRNA-expressing cells in the retina. Subsequently, we investigated the retina of the closely related bowhead whale (Balaena mysticetus; family Balaenidae) to determine how the loss of cone-mediated photoreception affects light signaling pathways in the retina. Anti-opsin immunofluorescence demonstrated the total loss of cone opsin expression in B. mysticetus, whereas light microscopy, transmission electron microscopy, and bipolar cell (protein kinase C-α [PKC-α] and recoverin) immunofluorescence revealed the maintenance of cone soma, putative cone pedicles, and both rod and cone bipolar cell types. These findings represent the first immunological and anatomical evidence of a naturally occurring rod-monochromatic mammalian retina, and suggest that despite the loss of cone-mediated photoreception, the associated cone signaling structures (i.e., cone synapses and cone bipolar cells) may be maintained for multichannel rod-based signaling in balaenid whales. J. Comp. Neurol. 524:2873-2885, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

    Justyna Widomska


    Full Text Available Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin. Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls, are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases.

  10. Spontaneous glial calcium waves in the retina develop over early adulthood.

    Kurth-Nelson, Zeb L; Mishra, Anusha; Newman, Eric A


    Intercellular glial Ca(2+) waves constitute a signaling pathway between glial cells. Artificial stimuli have previously been used to evoke these waves, and their physiological significance has been questioned. We report here that Ca(2+) waves occur spontaneously in rat retinal glial cells, both in the isolated retina and in vivo. These spontaneous waves are propagated by ATP release. In the isolated retina, suramin (P2 receptor antagonist) reduces the frequency of spontaneous wave generation by 53%, and apyrase (ATP-hydrolyzing enzyme) reduces frequency by 95-100%. Luciferin-luciferase chemiluminescence reveals waves of ATP matching the spontaneous Ca(2+) waves, indicating that ATP release occurs as spontaneous Ca(2+) waves are generated. Wave generation also depends on age. Spontaneous wave frequency rises from 0.27 to 1.0 per minute per mm(2), as rats age from 20 to 120 d. The sensitivity of glia to ATP does not increase with age, but the ATP released by evoked waves is 31% greater in 120-d-old than in 20-d-old rats, suggesting that increased ATP release in older animals could account for the higher frequency of wave generation. Simultaneous imaging of glial Ca(2+) and arterioles in the isolated retina demonstrates that spontaneous waves alter vessel diameter, implying that spontaneous waves may have a significant impact on retinal physiology. Spontaneous intercellular glial Ca(2+) waves also occur in the retina in vivo, with frequency, speed, and diameter similar to the isolated retina. Increased spontaneous wave occurrence with age suggests that wave generation may be related to retinal pathology.

  11. Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated rat retina.

    Tokuda, Kazuhiro; Zorumski, Charles F; Izumi, Yukitoshi


    Concerns have been raised about whether operating microscopes and endoillumination used during ophthalmic surgeries contribute to retinal damage. Despite the recognition that ascorbic acid (vitamin C) helps to protect the eye from light and the abundance of vitamin C in the retina, artificial aqueous humors used during surgery only contain the antioxidant glutathione. To test whether inclusion of antioxidants other than glutathione in surgical solutions might help to preserve retinal integrity, we studied the effects of vitamin C on acute toxicity in isolated rat retinas. Male Sprague-Dawley rats (PND 30+/-2) were sacrificed for retinal isolation. In the presence or absence of vitamin C (1 or 3 mM), retinas were exposed to 302 nm ultraviolet B (UVB) light for 1 h and were incubated for a total of 5 h at 30 degrees C. Retinal damage was assessed by morphological examination and biochemical assay measuring the amount of lactate dehydrogenase (LDH) released from injured cells. In control retinas, LDH release was significantly increased after UVB exposure. The presence of 1 mM vitamin C in the incubation media significantly reduced LDH release during the post-incubation period following UV exposure. No difference was found between 1 and 3 mM vitamin C. Microscopic examination revealed that disorganization in the outer nuclear layer after UVB exposure was markedly attenuated by administration of 1 mM vitamin C. Vitamin C (1 mM), a concentration found in the anterior chamber in humans, but not glutathione, prevented phototoxic injury following UV exposure. Although vitamin C itself cannot be used in intraocular irrigating solutions because of adverse interactions with iron released during bleeding, inclusion of antioxidants equivalent to vitamin C should be considered to help protect the retina from intraoperative light toxicity.

  12. Ptf1a triggers GABAergic neuronal cell fates in the retina

    Parain Karine


    Full Text Available Abstract Background In recent years, considerable knowledge has been gained on the molecular mechanisms underlying retinal cell fate specification. However, hitherto studies focused primarily on the six major retinal cell classes (five types of neurons of one type of glial cell, and paid little attention to the specification of different neuronal subtypes within the same cell class. In particular, the molecular machinery governing the specification of the two most abundant neurotransmitter phenotypes in the retina, GABAergic and glutamatergic, is largely unknown. In the spinal cord and cerebellum, the transcription factor Ptf1a is essential for GABAergic neuron production. In the mouse retina, Ptf1a has been shown to be involved in horizontal and most amacrine neurons differentiation. Results In this study, we examined the distribution of neurotransmitter subtypes following Ptf1a gain and loss of function in the Xenopus retina. We found cell-autonomous dramatic switches between GABAergic and glutamatergic neuron production, concomitant with profound defects in the genesis of amacrine and horizontal cells, which are mainly GABAergic. Therefore, we investigated whether Ptf1a promotes the fate of these two cell types or acts directly as a GABAergic subtype determination factor. In ectodermal explant assays, Ptf1a was found to be a potent inducer of the GABAergic subtype. Moreover, clonal analysis in the retina revealed that Ptf1a overexpression leads to an increased ratio of GABAergic subtypes among the whole amacrine and horizontal cell population, highlighting its instructive capacity to promote this specific subtype of inhibitory neurons. Finally, we also found that within bipolar cells, which are typically glutamatergic interneurons, Ptf1a is able to trigger a GABAergic fate. Conclusion Altogether, our results reveal for the first time in the retina a major player in the GABAergic versus glutamatergic cell specification genetic pathway.

  13. Palm is expressed in both developing and adult mouse lens and retina

    Galileo Deni S


    Full Text Available Abstract Background Paralemmin (Palm is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. Methods The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD and paralemmin2 (Palm2 in the lens and retina were determined by real time rt-PCR. Results In the lens, Palm is already expressed at 9.5 dpc in the lens placode, and this expression is maintained in the lens vesicle throughout the formation of the adult lens. Palm is largely absent from the optic vesicle but is detectable at 10.5 dpc in the optic cup. In the developing retina, Palm expression transiently upregulates during the formation of optic nerve as well as in the formation of both the inner and outer plexiform layers. In short term dissociated chick retinal cultures, Palm protein is easily detectable, but the levels appear to reduce sharply as the cultures age. Palm mRNA was found at much higher levels relative to Palm2 or PalmD in both the retina and lens. Conclusion Palm is the major paralemmin family member expressed in the retina and lens and its expression in the retina transiently upregulates during active neurite outgrowth. The expression pattern of Palm in the eye is consistent with it being a Pax6 responsive gene. Since Palm is known to be able to drive membrane formation in brain neurons, it is possible that this molecule is crucial for the increase in membrane formation during lens fiber cell differentiation.

  14. Cell differentiation in the retina of an epibenthonic teleost, the Tench (Tinca tinca, Linneo 1758).

    Bejarano-Escobar, Ruth; Blasco, Manuel; DeGrip, Willem J; Martín-Partido, Gervasio; Francisco-Morcillo, Javier


    Here we present a detailed study of the major events in the retinal histogenesis in a freshwater epibenthonic fish species, the Tench (Tinca tinca, Linneo 1758) during embryonic, prolarval, larval, and juvenile stages, using classical histological and immunohistological methods, providing a complete neurochemical characterization of retinal cells. We find a morphologically undifferentiated retina during embryonic stages and even at the hatching stage (postnatal day 0, P0). However, the emergence of the different retinal layers occurs in the first postnatal day (P1). Proliferating PCNA-positive cells are found in the retina of all postnatal individuals included in the present study, located in the circumferential germinal zone (CGZ), and in sparse cells dispersed throughout the inner nuclear layer (INL) and the outer nuclear layer (ONL). All neurochemical markers used start to express between P0 and P2. Anti-opsin, -alpha-protein kinase C, -alpha-tyrosine hydroxylase, -glutamine synthetase antibodies stain selectively different subpopulations of photoreceptor, bipolar, amacrine, and Müller cells respectively. Parvalbumin immunoreactivity is detected in amacrine and displaced amacrine cells. Several subpopulations of calretinin-positive ganglion, amacrine, and bipolar cells are detected in tench retina. Islet1 expression is confined to the nuclei of subpopulations of ganglion, amacrine, bipolar, and horizontal cells. All the maturational events described are first detected in the central retina and, as development progresses, they spread to the rest of the retina following a central-to-peripheral gradient. Therefore, tench postnatal retinal differentiation is a remarkable process not observed in the more common models of teleosts used in developmental biology.

  15. Pre-exposure to low-power diode laser irradiation promotes cytoprotection in the rat retina.

    Sun, Yue; Zhang, Shisheng; Liao, Huaping; Wang, Jing; Wang, Ling


    The aim of this study was to investigate whether pre-exposure to low-power laser irradiation can provoke an effect on cellular protection in the rat retina. The right eyes of 40 rats were exposed to a 3-mm diode laser beam for 1 min in different light intensities and different experimental sets: group A low power of 60 mW (34.27 J/cm(2) on the retina in consideration of the energy losses along the optical pathway) prior to high power of 80 mW (44.88 J/cm(2) on the retina in consideration of the energy losses along the optical pathway), group B high power, group C low power, group D (the left eyes from the counterpart of group A) and group E (untreated rat eyes) as controls. Morphological retinal change retinas were assessed using light microscopy and/or transmission electron microscopy. Heat shock protein (Hsp) 70 and cleaved caspase 3 protein expression were analyzed by immunohistochemical staining and Western blot. Cellular injury was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Hsp 70 expression in the inner plexiform layer and the outer plexiform layer in group A were 73.09 ± 6.49 and 78.03 ± 3.05%, respectively, which was significantly higher (P power laser irradiation stimulates a hyperexpression of Hsp70 together with a hypoexpression of cleaved caspase 3 in rat retina, which may suggest a cellular protective effect.

  16. CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina.

    Wang, Jing; Lin, Jihong; Schlotterer, Andreas; Wu, Liang; Fleming, Thomas; Busch, Stephanie; Dietrich, Nadine; Hammes, Hans-Peter


    Diabetes induces vasoregression, neurodegeneration and glial activation in the retina. Formation of advanced glycation endoproducts (AGEs) is increased in diabetes and contributes to the pathogenesis of diabetic retinopathy. CD74 is increased in activated microglia in a rat model developing both neurodegeneration and vasoregression. In this study, we aimed at investigating whether glucose and major AGE precursor methylglyoxal induce increased CD74 expression in the retina. Expression of CD74 in retinal microglia was analyzed in streptozotocin-diabetic rats by wholemount immunofluorescence. Nondiabetic mice were intravitreally injected with methylglyoxal. Expression of CD74 was studied by retinal wholemount immunofluorescence and quantitative real-time PCR, 48 h after the injection. CD74-positive cells were increased in diabetic 4-month retinas. These cells represented a subpopulation of CD11b-labeled activated microglia and were mainly located in the superficial vascular layer (13.7-fold increase compared to nondiabetic group). Methylglyoxal induced an 9.4-fold increase of CD74-positive cells in the superficial vascular layer and elevated gene expression of CD74 in the mouse retina 2.8-fold. In summary, we identified CD74 as a microglial activation marker in the diabetic retina. Exogenous methylglyoxal mimics the response in normoglycemic retina. This suggests that methylglyoxal is important in mediating microglial activation in the diabetic retina.

  17. Feasibility of 99mTc-TRODAT-1 Micro-SPECT imaging of dopamine transporter in animal retinas

    ZHAO Juan; QI Yujin; DAI Qiusheng; ZHANG Xuezhu; QU Xiaomei; HUANG Jia; LIU Xingdang


    In this paper, 99mTc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with form deprivation myopia. Pigmented guinea pigs aged 3 weeks were devided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6). The test group wore translucent goggles randomly for 4 weeks,and both groups underwent biometric measurement (refraction and axial length) before and after the experiment.Micro-SPECT retinas imaging was performed at the 4th week after injection of 99nTc-TRODAT-1. The retinas were clearly resolved in the images. The ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the control eye (15.20±1.98), and 2.35+1.05 lower than that in the fellow eyes (13.90±2.04). The results showed that 99mTc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina, and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes. Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.

  18. Preservation of cone photoreceptors after a rapid yet transient degeneration and remodeling in cone-only Nrl-/- mouse retina.

    Roger, Jerome E; Ranganath, Keerthi; Zhao, Lian; Cojocaru, Radu I; Brooks, Matthew; Gotoh, Norimoto; Veleri, Shobi; Hiriyanna, Avinash; Rachel, Rivka A; Campos, Maria Mercedes; Fariss, Robert N; Wong, Wai T; Swaroop, Anand


    Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor neural retina leucine zipper (NRL). The loss of Nrl (Nrl(-/-)) in mice results in a retina with predominantly S-opsin-containing cones that exhibit molecular and functional characteristics of wild-type cones. Here, we report that Nrl(-/-) retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by 4 months of age, resulting in a thinner but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic electroretinogram. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of genes related to stress response and inflammation, implying their involvement in cone death. The Nrl(-/-) mouse illustrates the long-term viability of cones in the absence of rods and retinal pigment epithelium defects in a rodless retina. We propose that Nrl(-/-) retina may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula.

  19. Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization

    ZHOU Xi-yuan; LIAO Qing; PU Yi-min; TANG Yong-qiang; GONG Xiao; LI Jia; XU Yan; WANG Zhi-gang


    microbubbles or ultrasound alone. In the rat CNV model, transfection efficiency mediated by ultrasound/microbubbles was significantly higher than that by lipofectamine-mediated gene transfer at 28 days after treatment. The study also showed that with the administration of ultrasound-mediated microbubbles destruction, the CNV of rats was inhibited effectively.Conclusions Ultrasound-microbubble technique could increase PEDF gene transfer into rats' retina and chorioid, in association with a significant inhibition of the development of CNV, suggesting that this noninvasive gene transfer method may provide a useful tool for clinical gene therapy.

  20. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

    Huddart, Robert A., E-mail: [Institute of Cancer Research, Royal Marsden NHSFT (National Health Service Foundation Trust) (United Kingdom); Hall, Emma [Institute of Cancer Research (United Kingdom); Hussain, Syed A. [University of Liverpool (United Kingdom); Jenkins, Peter [Gloucestershire Hospitals NHSFT (United Kingdom); Rawlings, Christine [South Devon Healthcare NHSFT (United Kingdom); Tremlett, Jean [Brighton and Sussex University Hospitals (United Kingdom); Crundwell, Malcolm [Royal Devon and Exeter NHSFT (United Kingdom); Adab, Fawzi A. [University Hospital of North Staffordshire NHS Trust (United Kingdom); Sheehan, Denise [Royal Devon and Exeter NHSFT (United Kingdom); Syndikus, Isabel [Clatterbridge Cancer Centre NHSFT (United Kingdom); Hendron, Carey [University of Birmingham (United Kingdom); Lewis, Rebecca; Waters, Rachel [Institute of Cancer Research (United Kingdom); James, Nicholas D. [University of Birmingham (United Kingdom)


    Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.

  1. Avaliação da autofluorescência do fundo de olho nas distrofias de retina com o aparelho Heidelberg Retina Angiograph2 Evaluation of fundus autofluorescence in hereditary retinal diseases using Heidelberg Retina Angiograph2

    Monique Côco


    Full Text Available OBJETIVOS: Definir características do exame de autofluorescência, verificando sua utilidade no diagnóstico e acompanhamento de distrofias retinianas. MÉTODOS: Participaram do estudo, 28 pacientes, adultos, divididos igualmente em quatro grupos com diagnósticos de doença de Stargardt, distrofia de Cones, retinose pigmentar e voluntários saudáveis para estabelecimento do padrão de normalidade. Em média foram obtidas nove imagens com o filtro para angiofluoresceinografia para a formação da imagem autofluorescente no Heidelberg Retina Angiograph2. As imagens de cada grupo de pacientes foram analisadas para verificar características comuns. RESULTADOS: As imagens fundoscópicas autofluorescentes dos voluntários do grupo controle mostraram área foveal hipoautofluorescente em relação à retina do pólo posterior. As imagens dos portadores de doença de Stargardt, em geral, apresentaram lesão hipoautofluorescente, correspondendo à área macular. As principais alterações da autofluorescência em pacientes com distrofia de cones foram hipoautofluorescência macular com halo hiperautofluorescente. Nos portadores de retinose pigmentar, foram encontrados pigmentos periféricos causando hipoautofluorescência. Na região macular, hipoautofluorescência ou apenas desorganização do pigmento. CONCLUSÃO: O estudo mostrou a existência de padrões de autofluorescência de fundo nas distrofias de retina que permitem o diagnóstico e melhor interpretação da fisiopatogenia destas doenças.PURPOSE: To define characteristics of the fundus autofluorescence examination, verifying usefulness in the diagnosis and care of hereditary retinal diseases. METHODS: 28 patients, adults, divided equally into four groups with diagnoses of Stargardt macular dystrophy, cone dystrophy, retinitis pigmentosa and healthy volunteers for the establishment of the normality pattern. An average of nine images with the filter for fluorescein angiography was obtained

  2. Ganglion cell size and distribution in the retina of the two-toed sloth (Choloepus didactylus L.).

    Andrade-da-Costa, B L; Pessoa, V F; Bousfield, J D; Clarke, R J


    The distribution of ganglion cell densities and sizes was studied in Nissl-stained flat-mount retinae of the two-toed sloth. The area centralis, a weak specialization with low ganglion cell density, is located in the temporal retina close to the center of the eye. The presence of a visual streak was noted. The distribution of different ganglion cell sizes was approximately equal throughout the retina. Although the retinal organization differs from that of the closely related three-toed sloth, the presumed function of retinal specializations in both species is to guide limb movements by permitting visualization of the branch along which the animal is climbing.

  3. Firebox modeling of SRT cracking heaters

    Sundaram, K.M.; Albano, J.V. [ABB Lummus Crest Inc., Bloomfield, NJ (United States)


    Thermal cracking of hydrocarbons remains the most economically attractive route for the production of ethylene. The heat for the endothermic cracking reaction is supplied in high capacity fired heaters which are designed specifically to have high selectivity to olefins. In the cracking process, coke is deposited within the tubes of the radiant coil. The rate of coke deposition in a cracking furnace is a function not only of process conditions but of other factors as well. High tube metal temperatures in certain areas of the coil or hot spots can cause locally high coking rate leading to partial blockage of the tubes and consequently, short runs. The small diameter tubes used in modern high selectivity heaters are more sensitive than older large tube designs. The occurrence of these hot zones is a strong function of fireside conditions. For satisfactory performance, the heat flux profile in a cracking heater must be maintained as uniform as possible. In addition, it is important to minimize the variation of process temperatures entering the various cracking coils. These fireside variables are not only a function of the type of burners, excess air, type of fuel(s) and distribution of air and fuel but depend significantly on the air and flue gas flow patterns associated with the firebox, i.e., the firebox aerodynamics. Poor aerodynamics can adversely affect firing patterns and hence heat flux profiles in commercial furnaces. A variety of modeling techniques have been used to evaluate the firebox aerodynamics of Lummus, Short Residence Time, cracking heaters. These include flow visualization, physical cold flow modeling, and computational techniques. These approaches are discussed in this paper.

  4. A wideband spectrometer for the SRT

    Comoretto, G.; Natale, V.

    A radiotelescope operating at millimeter wavelengths must be able to analyze an instantaneous bandwidth of at least a few GHz in spectroscopic mode, with a number of spectral points of the order of thousands. Two solutions are examined. In the first, it is assumed that a multi-channel digital spectrometer, with a bandwidth of the order of 100 MHz for each channel, will be available. In this case, a digital filterbank derived from the experience with the ALMA correlator could be used to synthesize a total bandwidth of 1-2 GHz. For wider bandwidths, an acousto-optical spectrometer is proposed. The experience at IRA, Sez. di Firenze with these instruments is presented, and possible solutions are outlined.

  5. Glio-vascular modifications caused by Aquaporin-4 deletion in the mouse retina.

    Nicchia, Grazia Paola; Pisani, Francesco; Simone, Laura; Cibelli, Antonio; Mola, Maria Grazia; Dal Monte, Massimo; Frigeri, Antonio; Bagnoli, Paola; Svelto, Maria


    Aquaporin-4 (AQP4) is the Central Nervous System water channel highly expressed at the perivascular glial domain. In the retina, two types of AQP4 expressing glial cells take part in the blood-retinal barrier (BRB), astrocytes and Müller cells. The aim of the present study is to investigate the effect of AQP4 deletion on the retinal vasculature by looking at typical pathological hallmark such as BRB dysfunction and gliotic condition. AQP4 dependent BRB properties were evaluated by measuring the number of extravasations in WT and AQP4 KO retinas by Evans blue injection assay. AQP4 deletion did not affect the retinal vasculature, as assessed by Isolectin B4 staining, but caused BRB impairment to the deep plexus capillaries while the superficial and intermediate capillaries were not compromised. To investigate for gliotic responses caused by AQP4 deletion, Müller cells and astrocytes were analysed by immunofluorescence and western blot, using the Müller cell marker Glutamine Synthetase (GS) and the astrocyte marker GFAP. While GS expression was not altered in AQP4 KO retinas, a strong GFAP upregulation was found at the level of AQP4 KO astrocytes at the superficial plexus and not at Müller cells at the intermediate and deep plexi. These data, together with the upregulation of inflammatory markers (TNF-α, IL-6, IL-1β and ICAM-1) in AQP4 KO retinas indicated AQP4 deletion as responsible for a gliotic phenotype. Interestingly, no GFAP altered expression was found in AQP4 siRNA treated astrocyte primary cultures. All together these results indicate that AQP4 deletion is directly responsible for BRB dysfunction and gliotic condition in the mouse retina. The selective activation of glial cells at the primary plexus suggests that different regulatory elements control the reaction of astrocytes and Müller cells. Finally, GFAP upregulation is strictly linked to gliovascular crosstalk, as it is absent in astrocytes in culture. This study is useful to understand the role

  6. Doublecortin is widely expressed in the developing and adult retina of sharks.

    Sánchez-Farías, Nuria; Candal, Eva


    Doublecortin (DCX) is a microtubule-associated protein that has been considered a marker for neuronal precursors and young migrating neurons during the development of the central nervous system and in adult neurogenic niches. The retina of fishes represents an accessible, continuously growing and highly structured (layered) part of the central nervous system and, therefore, offers an exceptional model to extend our knowledge on the possible role of DCX in promoting neurogenesis and migration to appropriate layers. We have analyzed the distribution of DCX in the embryonic and postembryonic retina of a small shark, the lesser spotted dogfish Scyliorhinus canicula, by means of immunohistochemistry. We investigated the relationship between DCX expression and the neurogenic state of DCX-labeled cells by exploring its co-localization with the proliferation marker PCNA (proliferating cell nuclear antigen) and the marker of neuronal differentiation HuC/D. Since radially migrating neurons use radial glial fibers as substrate, we explored the possible correlation between DCX expression and cell migration along radial glia by comparing its expression with that of the glial marker GFAP (glial fibrillary acidic protein). Additionally, we characterized DCX-expressing cells by double immunocytochemistry using antibodies against Calbindin (a marker for mature bipolar and horizontal cells in this species) and Pax6, which has been proposed as a regulator of cell proliferation, cell differentiation, and neuron diversification in the neural retina of sharks. Strong DCX immunoreactivity was observed in immature cells and cell processes, at a time when retinal cells were not yet organized into different laminae. DCX was also found in subsets of mature ganglion, amacrine, bipolar and horizontal cells long after they had exited the cell cycle, a pattern that was maintained in juveniles and adults. Our results on DCX expression in the retina are compatible with a role for DCX in cell

  7. In vitro differentiation of MSCs into retina-like cells by the supernatant fluid of light-injured neurosensory retina%光损伤鼠视网膜片培养上清液诱导 MSCs 分化为视网膜样细胞的研究

    白月; 徐国兴


    AIM: To explore the possibility of inducing rat mesenchymal stem cells ( MSCs) into retina-like cells by the supernatant fluid of light-injured neurosensory retina in vitro. METHODS: MSCs were isolated and attached to the wall of culture dishes by their specific adherent ability. Then the cells were characterized by flow cytometry.The neurosensory retina was isolated from retina of SD rat and it was tested by hematoxylin-eosin ( HE ) staining.The pathological changes of light-injured neurosensory retina was observed under transmission electron microscope. Three kinds of supernatant fluid of light -injured neurosensory retina of SD rats were prepared.The third passage of MSCs were cultured with these mixed medium for 7-8d, we used RT-PCR to see whether they could express rhodopsin, neuron-specific enolase (NSE), and glial fibrillary acidic protein ( GFAP ) , and positive cells were counted and analyzed. RESULTS: HE staining showed the retinal sheets included full-thickness neural retina.Neurosensory retina developed ultrastructural destructions by light injury.RT-PCR showed that the medium of mixed I expressed higher positive rate of rhodopsin (0.3915±0.00644), NSE (0.2019± 0.00682), GFAP (0.1972 ±0.00211) than the medium of mixed Ⅱ rhodopsin (0.0983 ±0.00319), NSE (0.1048 ± 0.00323), GFAP (0.1040±0.00254) and medium of mixedⅢrhodopsin(0.0044±0.00126), NSE (0.0498±0.00149), GFAP (0.0467±0.00333).The difference of intergroup has statistical significance. CONCLUTION:The supernatant fluid of light-injured neurosensory retina of SD rats can induce MSCs to differentiate into retina-like cells and provide new insights of stem cell therapy for retinopathy.%目的:应用大鼠视网膜片光损伤后的培养上清液,在体外诱导大鼠骨髓间充质干细胞( mesenchymal stem cells , MSCs)成为视网膜样细胞的可能性。  方法:贴壁筛选法分离、培养大鼠MSCs ,流式细胞仪对其细胞纯度鉴定。取材大鼠视网

  8. Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging.

    Han, Meng; Giese, Guenter; Schmitz-Valckenberg, Steffen; Bindewald-Wittich, Almut; Holz, Frank G; Yu, Jiayi; Bille, Josef F; Niemz, Markolf H


    The intensive metabolism of photoreceptors is delicately maintained by the retinal pigment epithelium (RPE) and the choroid. Dysfunction of either the RPE or choroid may lead to severe damage to the retina. Two-photon excited autofluorescence (TPEF) from endogenous fluorophores in the human retina provides a novel opportunity to reveal age-related structural abnormalities in the retina-choroid complex prior to apparent pathological manifestations of age-related retinal diseases. In the photoreceptor layer, the regularity of the macular photoreceptor mosaic is preserved during aging. In the RPE, enlarged lipofuscin granules demonstrate significantly blue-shifted autofluorescence, which coincides with the depletion of melanin pigments. Prominent fibrillar structures in elderly Bruch's membrane and choriocapillaries represent choroidal structure and permeability alterations. Requiring neither slicing nor labeling, TPEF imaging is an elegant and highly efficient tool to delineate the thick, fragile, and opaque retina-choroid complex, and may provide clues to the trigger events of age-related macular degeneration.

  9. Microscopic hyperspectral imaging studies of normal and diabetic retina of rats

    LI QingLi; XUE YongQi; ZHANG JingFa; XIAO GongHai


    A microscopic hyperspectral imager was developed based on the microscopic technology and the spectral imaging technology. Some microscopic hyperspectral images of retina seotions of the normal, the diabetic, and the treated rats were collected by the new imager. Single-band images and pseudo-color Images of each group were obtained and the typical transmittance spectrums were ex-tracted. The results showed that the transmittance of outer nuclear layer cells of the diabetic group was generally higher than that of the normal. A small absorption peak appeared near the 180th band in the spectrum of the diabetic group and this peak weakened or disappeared in the spectrum of the treated group. Our findings indicate that the microscopic hyperspectral images include wealthy information of retina sections which is helpful for the ophthalmologist to reveal the pathogenesis of diabetic reti-nopathy and explore the therapeutic effect of drugs.

  10. Bipolar cell pathways for color and luminance vision in a dichromatic mammalian retina.

    Li, Wei; DeVries, Steven H


    The mammalian retina is fundamentally dichromatic, with trichromacy only recently emerging in some primates. In dichromats, an array of short wavelength-sensitive (S, blue) and middle wavelength-sensitive (M, green) cones is sampled by approximately ten bipolar cell types, and the sampling pattern determines how retinal ganglion cells and ultimately higher visual centers encode color and luminance. By recording from cone-bipolar cell pairs in the retina of the ground squirrel, we show that the bipolar cell types sample cone signals in three ways: one type receives input exclusively from S-cones, two types receive mixed S/M-cone input and the remaining types receive an almost pure M-cone signal. Bipolar cells that carry S- or M-cone signals can have a role in color discrimination and may contact color-opponent ganglion cells. Bipolar cells that sum signals from S- and M-cones may signal to ganglion cells that encode luminance.

  11. Aberration-free volumetric high-speed imaging of in vivo retina

    Hillmann, Dierck; Hain, Carola; Sudkamp, Helge; Franke, Gesa; Pfäffle, Clara; Winter, Christian; Hüttmann, Gereon


    Research and medicine rely on non-invasive optical techniques to image living tissue with high resolution in space and time. But so far a single data acquisition could not provide entirely diffraction-limited tomographic volumes of rapidly moving or changing targets, which additionally becomes increasingly difficult in the presence of aberrations, e.g., when imaging retina in vivo. We show, that a simple interferometric setup based on parallelized optical coherence tomography acquires volumetric data with 10 billion voxels per second, exceeding previous imaging speeds by an order of magnitude. This allows us to computationally obtain and correct defocus and aberrations resulting in entirely diffraction-limited volumes. As demonstration, we imaged living human retina with clearly visible nerve fiber layer, small capillary networks, and photoreceptor cells, but the technique is also applicable to obtain phase-sensitive volumes of other scattering structures at unprecedented acquisition speeds.

  12. Microscopic hyperspectral imaging studies of normal and diabetic retina of rats


    A microscopic hyperspectral imager was developed based on the microscopic technology and the spectral imaging technology. Some microscopic hyperspectral images of retina sections of the normal, the diabetic, and the treated rats were collected by the new imager. Single-band images and pseudo-color images of each group were obtained and the typical transmittance spectrums were ex-tracted. The results showed that the transmittance of outer nuclear layer cells of the diabetic group was generally higher than that of the normal. A small absorption peak appeared near the 180th band in the spectrum of the diabetic group and this peak weakened or disappeared in the spectrum of the treated group. Our findings indicate that the microscopic hyperspectral images include wealthy information of retina sections which is helpful for the ophthalmologist to reveal the pathogenesis of diabetic reti-nopathy and explore the therapeutic effect of drugs.

  13. Automated pathologies detection in retina digital images based on complex continuous wavelet transform phase angles.

    Lahmiri, Salim; Gargour, Christian S; Gabrea, Marcel


    An automated diagnosis system that uses complex continuous wavelet transform (CWT) to process retina digital images and support vector machines (SVMs) for classification purposes is presented. In particular, each retina image is transformed into two one-dimensional signals by concatenating image rows and columns separately. The mathematical norm of phase angles found in each one-dimensional signal at each level of CWT decomposition are relied on to characterise the texture of normal images against abnormal images affected by exudates, drusen and microaneurysms. The leave-one-out cross-validation method was adopted to conduct experiments and the results from the SVM show that the proposed approach gives better results than those obtained by other methods based on the correct classification rate, sensitivity and specificity.

  14. The electroretinogram as a method for studying circadian rhythms in the mammalian retina

    Morven A. Cameron; Alun R. Barnard; Robert J. Lucas


    Circadian clocks are thought to regulate retinal physiology in anticipation of the large variation in environmental irradiance associated with the earth’s rotation upon its axis. In this review we discuss some of the rhythmic events that occur in the mammalian retina, and their consequences for retinal physiology. We also review methods of tracing retinal rhythmicity in vivo and highlight the electroretinogram (ERG) as a useful technique in this field. Principally, we discuss how this technique can be used as a quick and noninvasive way of assessing physiological changes that occur in the retina over the course of the day. We highlight some important recent findings facilitated by this approach and discuss its strengths and limitations.

  15. Isolation of progenitor cells from GFP-transgenic pigs and transplantation to the retina of allorecipients

    Klassen, Henry; Warfvinge, Karin; Schwartz, Philip H


    to survival as allografts and integrate into the host retinal architecture, we isolated donor cells from fetal green fluorescent protein (GFP)-transgenic pigs. Cultures were propagated from the brain, retina, and corneo-scleral limbus. GFP expression rapidly increased with time in culture, although lower......Work in rodents has demonstrated that progenitor transplantation can achieve limited photoreceptor replacement in the mammalian retina; however, replication of these findings on a clinically relevant scale requires a large animal model. To evaluate the ability of porcine retinal progenitor cells...... in conjunction with photoreceptor markers and glial fibrillary acid protein (GFAP), thus suggesting downregulation of GFP during differentiation. Following transplantation, GFP expression allowed histological visualization of integrated cells and extension of fine processes to adjacent plexiform layers. GFP...

  16. Readout circuit design of the retina-like CMOS image sensor

    Cao, Fengmei; Song, Shengyu; Bai, Tingzhu; Cao, Nan


    Readout circuit is designed for a special retina-like CMOS image sensor. To realize the pixels timing drive and readout of the sensor, the Altera's Cyclone II FPGA is used as a control chip. The voltage of the sensor is supported by a voltage chip initialized by SPI with AVR MCU system. The analog image signal outputted by the sensor is converted to digital image data by 12-bits A/D converter ADS807 and the digital data is memorized in the SRAM. Using the Camera-link image grabber, the data stored in SRAM is transformed to image shown on PC. Experimental results show the circuit works well on retina-like CMOS timing drive and image readout and images can be displayed properly on the PC.

  17. Distribution and protective function of pituitary adenylate cyclase-activating polypeptide (PACAP in the retina

    Tomoya eNakamachi


    Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP, which is found in 27- or 38-amino acid forms, belongs to the VIP/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues, with PACAP known to exert a protective effect against several types of neural damage. The retina is considered to be part of the central nervous system, and retinopathy is a common cause of profound and intractable loss of vision. This review will examine the expression and morphological distribution of PACAP and its receptors in the retina, and will summarize the current state of knowledge regarding the protective effect of PACAP against different kinds of retinal damage, such as that identified in association with diabetes, ultraviolet light, hypoxia, optic nerve transection, and toxins. This article will also address PACAP-mediated protective pathways involving retinal glial cells.

  18. Electroretinography: A biopotential to assess the function/dysfunction of the retina

    Quintana, Quinteros; Benedetto, M. L.; Maldonado, M. M.; de Payer E., A. C. Vera; Contin, M. A.


    The Electroretinography (ERG) is a noninvasive technique that allows the assessment of functional integrity of the retina. The ERG recordings are biopotencials acquired in the corneal surface as a response of retinal tissue against controlled light stimuli. In clinical ophthalmology ERG is not commonly used but nowadays, because of the high incidence of degenerative diseases of the retina (RD), its use should be increased. Like other biopotentials as electrocardiography (ECG), electroencephalogram (EEG) and electromyography (EMG), ERG is a low amplitude signal, in this case a few hundred of microvolts (µV), which must be fitted and processed. The ERG signals are affected in morphology in the presence of pathologies that affects the integrity of the different retinal cell groups, for example due to some RD. In advanced cases of RD recordings can be abolished in the time domain; and yet in them it is believed that there is relevant clinical information making the ERG a great potential diagnostic tool.

  19. [Relationship between vitrectomy and the morphology and function of the retina].

    Terasaki, Hiroko


    Pathological processes in the vitreous will be reflected in the morphology and function of the retina, and these processes can originate from sources outside the vitreous. The purpose of vitreous surgery is to remove the qualitatively and/or morphologically diseased vitreous. Successful vitrectomy will be manifested by an improvement in the structure and/or function of the retina. We have evaluated the morphology of the vitreoretinal interface, and the function of the retina before and after vitreous surgery. Plasmin-assisted vitrectomy was used in some cases to remove the diseased vitreous more efficiently and less invasively. The effect of this procedure was assessed by examining the morphology and function of the retina. First, the relationship between the qualitative and structural abnormality of the vitreous in macular diseases was studied. In aphakic/pseudophakic eyes with cystoid macular edema, there was a depression of retinal function over the entire retina which may have been caused by chemical mediators released into the vitreous. These mediators may have been produced by inflammation in the anterior segment of the eye. In eyes with an idiopathic macular hole, optical coherence tomographic (OCT) images suggested that the progression of the macular hole might depend on a balance between foveal adhesion and the posterior vitreous. Second, the efficacy, surgical damage, and limitations of vitreous surgery were investigated. The recovery of macular function was assessed by focal macular electroretinograms (FMERGs) after vitrectomy for epiretinal membrane, choroidal neovascularization, and diabetic macular edema. The concurrent examination by optical coherence tomography (OCT) suggested that a decrease in retinal thickness contributed to the functional recovery. Macular functional recovery was delayed and limited after macular translocation, diabetic macular edema, and internal limiting membrane peeling. Third, we studied the effect of plasmin

  20. Aberration-free volumetric high-speed imaging of in vivo retina

    Hillmann, Dierck; Spahr, Hendrik; Hain, Carola; Sudkamp, Helge; Franke, Gesa; Pfäffle, Clara; Winter, Christian; Hüttmann, Gereon


    Certain topics in research and advancements in medical diagnostics may benefit from improved temporal and spatial resolution during non-invasive optical imaging of living tissue. However, so far no imaging technique can generate entirely diffraction-limited tomographic volumes with a single data acquisition, if the target moves or changes rapidly, such as the human retina. Additionally, the presence of aberrations may represent further difficulties. We show that a simple interferometric setup-based on parallelized optical coherence tomography-acquires volumetric data with 10 billion voxels per second, exceeding previous imaging speeds by an order of magnitude. This allows us to computationally obtain and correct defocus and aberrations resulting in entirely diffraction-limited volumes. As demonstration, we imaged living human retina with clearly visible nerve fiber layer, small capillary networks, and photoreceptor cells. Furthermore, the technique can also obtain phase-sensitive volumes of other scattering structures at unprecedented acquisition speeds.

  1. Where do the photons collapse - in the retina or in the brain cortex?

    Georgiev, D D


    While looking for evidence of quantum coherent states within the brain many quantum mind advocates proposed experiments based on the assumption that the coherence state of natural light could somehow be preserved thorough the neural processing, or in other words they suppose that photons collapse not in the retina, but in the brain cortex. In this paper I show that photons collapse within the retina and subsequent processing of information at the level of neural membranes proceeds. The changes of the membrane potential of the neurons in the primary sensory cortical regions are shown to be relevant to inputting sensory information, which is converted into microtubule subunits pattern and specific quantum states. The role of the associative cortical regions in the conscious experience is thoroughly revised. One of the strangest observations, namely the existence of the so called grandmother cells, is explained by quantum state processing. The question why classical computing is needed at all gets unexpected ans...


    陈燕; 孙悦


    <正>Objective To determine the changes of retina nerve fiber thickness with optical coherence tomography(OCT) in Alzheimer’s disease(AD) patients.Methods OCT was used to measure the thickness of retinal nerve fiber layer(RNFL) from 38 AD patients and 26 healthy age-matched controls.The corrected visual acuity and intraocular pressure were measured and the dilated fundus examinations were also performed in those subjects.Results Compared with healthy age-matched controls,the RNFL thickness of AD patients(95.40±29.45) were much thinner than the controls(105.91±29.87)(P <().05),especially in superior quadrant,while no difference was found in the other retinal area.Conclusion Retinal nerve degeneration may be present in the retina of AD patients and this degeneration is likely localized preferentially to the superior quadrant.

  3. Differential effects of nitric oxide on rod and cone pathways in carp retina

    叶冰; 杜久林; 杨雄里


    The effects of nitric oxide (NO) on electroretinograms and light responses of horizontal cells intra-cellularly recorded from isolated, superfused carp retinas were studied. Sodium nitroprusside (SNP), an NO donor, suppressed scotopic b wave, while enhancing photopic b wave, and the effects could be blocked by hemoglobin, an NO chelator. Furthermore, following SNP application, light responses of rod horizontal cells were reduced in size and those of cone horizontal cells were increased. These results suggest that NO suppresses the activity of rod pathway, but enhances that of cone pathway in the outer retina. Moreover, the effects of methylene blue, an inhibitor of soluble guanylate cyclase, on rod and cone horizontal cells were just opposite to those of SNP, implying that the effects of NO may be mediated by cGMP.

  4. Simulation of cellular changes on Optical Coherence Tomography of human retina.

    Santos, Miriam; Araujo, Aderito; Barbeiro, Silvia; Caramelo, Francisco; Correia, Antonio; Marques, Maria Isabel; Pinto, Luis; Serranho, Pedro; Bernardes, Rui; Morgado, Miguel


    We present a methodology to assess cell level alterations on the human retina responsible for functional changes observable in the Optical Coherence Tomography data in healthy ageing and in disease conditions, in the absence of structural alterations. The methodology is based in a 3D multilayer Monte Carlo computational model of the human retina. The optical properties of each layer are obtained by solving the Maxwell's equations for 3D domains representative of small regions of those layers, using a Discontinuous Galerkin Finite Element Method (DG-FEM). Here we present the DG-FEM Maxwell 3D model and its validation against Mie's theory for spherical scatterers. We also present an application of our methodology to the assessment of cell level alterations responsible for the OCT data in Diabetic Macular Edema. It was possible to identify which alterations are responsible for the changes observed in the OCT scans of the diseased groups.

  5. Rax: Developmental and Daily Expression Patterns in the Rat Pineal Gland and Retina

    Rohde, Kristian; Klein, David C; Møller, Morten;


    Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change...... significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax...... transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes...

  6. Developmental and mutational changes of glycoproteins in the mouse neuronal retina: studies with bovine galactosyltransferase.

    Wallenfels, B


    Bovine galactosyltransferase (lactose synthase; EC which catalyzes the transfer of galactose from UDPgalactose to glycoproteins with N-acetylglucosamine as the terminal residue of their oligosaccharide side chains was used to label glycoproteins of mouse retina with [14C]galactose. The glycoproteins were separated by isoelectric focusing in the first dimension and by sodium dodecyl sulfate gel electrophoresis in the second dimension. Their position on the gel was determined by autofluorography. With this method, quantitative as well as qualitative changes in the glycoprotein composition of the neuronal mouse retina during postnatal development were observed. Furthermore, it was found that the photoreceptor loss in mice with retinal degeneration was paralleled by the disappearance of certain glycoprotein bands.

  7. Dynamic molecular monitoring of retina inflammation by in vivo Raman spectroscopy coupled with multivariate analysis.

    Marro, Monica; Taubes, Alice; Abernathy, Alice; Balint, Stephan; Moreno, Beatriz; Sanchez-Dalmau, Bernardo; Martínez-Lapiscina, Elena H; Amat-Roldan, Ivan; Petrov, Dmitri; Villoslada, Pablo


    Retinal tissue is damaged during inflammation in Multiple Sclerosis. We assessed molecular changes in inflamed murine retinal cultures by Raman spectroscopy. Partial Least Squares-Discriminant analysis (PLS-DA) was able to classify retina cultures as inflamed with high accuracy. Using Multivariate Curve Resolution (MCR) analysis, we deconvolved 6 molecular components suffering dynamic changes along inflammatory process. Those include the increase of immune mediators (Lipoxygenase, iNOS and TNFα), changes in molecules involved in energy production (Cytochrome C, phenylalanine and NADH/NAD+) and decrease of Phosphatidylcholine. Raman spectroscopy combined with multivariate analysis allows monitoring the evolution of retina inflammation. Copyright © 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. [Stem cells in adult retina--current state of research, future therapeutic prospects].

    Machalińska, Anna; Zuba-Surma, Ewa K


    The latest research reports revealed the presence of stem/progenitor cells located in different regions of matured eye. They are able to differentiate into retinal pigment epithelium cells as well as neural structure of retina. These cells were identified in neurosensory retina, pigment epithelium and within cilliary body and iris epithelium. Moreover, it has been proved that Muller glia possess the potential of differentiation into retinal cells. These findings indicate the presence of potential mechanisms enabling retinal cell repopulation and retinal tissue regeneration. In the present work, the recent reports documenting the presence of different stem cell populations in eye have been reviewed, particularly focusing on recently identified very small embryonic-like stem cells (VSEL-SCs). The potential clinical applications of the residing stem cells and limitations of such therapeutic strategies have been also discussed.

  9. Modelación y simulación de la retina humana

    Andrés Castaño


    Full Text Available

    Las enfermedades de la retina causan pérdida de la visión de varios
    grados de severidad; las causas son múltiples y en la mayoría de los casos irreversibles. En los últimos años se ha venido desarrollando investigación en el campo de la visión artificial y la visión por computador, alrededor de todo el mundo. Nuestro proyecto pretende desarrollar un modelo matemático de la retina, implementar la solución numérica en MATLAB™ y posteriormente construir un dispositivo electrónico que implemente el modelo y la solución numérica.



  10. The area centralis in the chicken retina contains efferent target amacrine cells

    Weller, Cynthia; Lindstrom, Sarah H.; De Grip, Willem J.; Wilson, Martin


    The retinas of birds receive a substantial efferent, or centrifugal, input from a midbrain nucleus. The function of this input is presently unclear but previous work in the pigeon has shown that efferent input is excluded from the area centralis, suggesting that the functions of the area centralis and the efferent system are incompatible. Using an antibody specific to rods, we have identified the area centralis in another species, the chicken, and mapped the distribution of the unique amacrine cells that are the postsynaptic partners of efferent fibers. Efferent target amacrine cells are found within the chicken area centralis and their density is continuous across the border of the area centralis. In contrast to the pigeon retina then, we conclude that the chicken area centralis receives efferent input. We suggest that the difference between the 2 species is attributable to the presence of a fovea within the area centralis of the pigeon and its absence from that of the chicken. PMID:19296862

  11. Artificial design of three-dimensional retina-like tissue from dissociated cells of the mammalian retina by rotation-mediated cell aggregation.

    Rothermel, Andrée; Biedermann, Thomas; Weigel, Winnie; Kurz, Randy; Rüffer, Markus; Layer, Paul G; Robitzki, Andrea Anneliese


    The goal of this study was to establish a reliable three-dimensional culture system for the mammalian retina that allows the analysis of retinal function and dysfunction. To produce three-dimensional retinal tissues in vitro, dissociated retinal cells of neonatal rats were maintained in culture dishes on a self-made orbital shaker. On the basis of well-defined rotation conditions, dissociated free-floating cells reaggregate in the center of the culture dish to form a multicellular cluster. Subsequently, cells begin to proliferate, whereby they form spherelike retinal tissues that grow to a size of 180-210 microm. Immunohistochemical characterization of mature retinal spheres revealed the presence of ganglion cells, amacrine cells, Müller cells, and rod photoreceptors, which are arranged in different retina-like layers. Although a small number of cells undergo programmed cell death, retinal spheres remain viable for at least 35 days in culture as revealed by fluorescein diacetate and TUNEL staining. Because most biological processes involved in tissue organization such as proliferation, differentiation, apoptosis, and survival are also observable in retinal spheres, the presented novel mammalian three-dimensional culture system is not only an outstanding model for basic research but may also be of great benefit for stem cell tissue engineering and the pharmaceutical industry.

  12. Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development.

    Kim, Jung-Woong; Jang, Sang-Min; Kim, Chul-Hong; An, Joo-Hee; Choi, Kyung-Hee


    Neural retina leucine zipper (Nrl), a key basic motif leucine zipper (bZIP) transcription factor, modulates rod photoreceptor differentiation by activating rod-specific target genes. In searching for factors that might couple with Nrl to modulate its transcriptional activity through posttranslational modification, we observed the novel interactions of Nrl with c-Jun N-terminal kinase 1 (JNK1) and HIV Tat-interacting protein 60 (Tip60). JNK1 directly interacted with and phosphorylated Nrl at serine 50, which enhanced Nrl transcriptional activity on the rhodopsin and Ppp2r5c promoters. Use of an inactive JNK1 mutant or treatment with a JNK inhibitor (SP600125) significantly reduced JNK1-mediated phosphorylation and transcriptional activity of Nrl in cultured retinal explants. We also found that Nrl activated rhodopsin and Ppp2r5c transcription by recruiting Tip60 to promote histone H3/H4 acetylation. The binding affinity of phospho-Nrl for Tip60 was significantly greater than that of the unphosphorylated Nrl. Thus, the histone acetyltransferase-containing Tip60 behaved as a coactivator in the Nrl-dependent transcriptional regulation of the rhodopsin and Ppp2r5c genes in the developing mouse retina. A transcriptional network of interactive proteins, including Nrl, JNK1, and Tip60, may be required to precisely control spatiotemporal photoreceptor-specific gene expression during retinal development.

  13. Potassium-stimulated release of radiolabelled taurine and glycine from the isolated rat retina

    Smith, L.F.; Pycock, C.J.


    The release of preloaded (/sup 3/H)glycine and (/sup 3/H)taurine in response to a depolarising stimulus (12.5-50 mM KCl) has been studied in the superfused rat retina. High external potassium concentration immediately increased the spontaneous efflux of (/sup 3/H)glycine, the effect of 50 mM K+ apparently being abolished by omitting calcium from the superfusing medium. In contrast, although high potassium concentrations increased the spontaneous efflux of (/sup 3/H)taurine from the superfused rat retina, this release was not evident until the depolarising stimulus was removed from the superfusing medium. The magnitude of this late release of (/sup 3/H)taurine was dependent on external K+ concentrations, and appeared immediately after cessation of the stimulus irrespective of whether it was applied for 4, 8, or 12 min. Potassium (50 mM)-induced release of taurine appeared partially calcium-dependent, being significantly reduced (p less than 0.01) but not abolished by replacing calcium with 1 mM EDTA in the superfusate. High-affinity uptake systems for both (/sup 3/H)glycine and (/sup 3/H)taurine were demonstrated in the rat retina in vitro (Km values, 1.67 microM and 2.97 microM; Vmax values, 19.3 and 23.1 nmol/g wet weight tissue/h, respectively). The results are discussed with respect to the possible neurotransmitter roles of both amino acids in the rat retina.

  14. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells.

    Li, Tianqing; Lewallen, Michelle; Chen, Shuyi; Yu, Wei; Zhang, Nian; Xie, Ting


    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptor-deficient mice, but there is still some concern of tumor formation. In this study, we have successfully cultured Nestin(+)Sox2(+)Pax6(+) multipotent retinal stem cells (RSCs) from the adult mouse retina, which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation. After they have been expanded for over 35 passages in the presence of FGF and EGF, the cultured RSCs still maintain stable proliferation and differentiation potential. Under proper differentiation conditions, they can differentiate into all the major retinal cell types found in the adult retina. More importantly, they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions. Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes, RSC-derived photoreceptor cells integrate into the retina, morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons. When transplanted into eyes of photoreceptor-deficient rd1 mutant mice, a RP model, RSC-derived photoreceptors can partially restore light response, indicating that those RSC-derived photoreceptors are functional. Finally, there is no evidence for tumor formation in the photoreceptor-transplanted eyes. Therefore, this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  15. Developmental expression of neurokinin-1 and neurokinin-3 receptors in the rat retina.

    Casini, G; Brecha, N C; Bosco, L; Rickman, D W


    Tachykinin (TK) peptides act on retinal neurons through neurokinin (NK) receptors. We examined the expression of neurokinin-1 (NK1; the substance P receptor), NK3 [the neurokinin B (NKB) receptor], and TK peptides in developing rat retinas. NK1 immunolabeling was found in newborn retinas in rare amacrine cells and in putative ganglion cells. At postnatal day 2 (PND 2), NK1 immunostaining was reduced greatly among ganglion cells, and it appeared in many amacrine cells and in fibers in the inner plexiform layer (IPL), with the highest density in laminae 1, 3, and 5. A similar pattern was found at PND 7. At PND 12, interplexiform NK1-immunoreactive (-IR) cells were detected, and NK1-IR fibers in the IPL were concentrated in lamina 2, similar to what was seen in adults. NK3 was expressed mainly by OFF-cone bipolar cells, and the developmental pattern of NK3 was compared with that of cone bipolar cells that were labeled with antibodies to recoverin. Immature recoverin-IR cone bipolar cells were seen at PND 2. NK3 immunolabeling was detected first in the outer plexiform layer and in sparse bipolar cell somata at PND 10, when recoverin-IR cone bipolar cells are nearly mature. By PND 15, both the NK3 immunostaining pattern and the recoverin immunostaining pattern were similar to the patterns seen in adults. TK immunoreactivity was present at PND 0 in amacrine cells and displaced amacrine cells. By PND 10, the morphologic maturation of TK-IR cells was complete. These findings indicate that, in early postnatal retinas, substance P may act on NK1 receptors, whereas NKB/NK3 interactions are unlikely, suggesting that there are different levels of importance for different TK peptides in the developing retina. Copyright 2000 Wiley-Liss, Inc.

  16. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells

    Tianqing Li; Michelle Lewallen; Shuyi Chen; Wei Yu; Nian Zhang; Ting Xie


    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases,such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptordeficient mice,but there is still some concern of tumor formation.In this study,we have successfully cultured Nestin+Sox2+Pax6+ multipotent retinal stem cells (RSCs) from the adult mouse retina,which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation.After they have been expanded for over 35 passages in the presence of FGF and EGF,the cultured RSCs still maintain stable proliferation and differentiation potential.Under proper differentiation conditions,they can differentiate into all the major retinal cell types found in the adult retina.More importantly,they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions.Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes,RSC-derived photoreceptor cells integrate into the retina,morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons.When transplanted into eyes of photoreceptor-deficient rd1 mutant mice,a RP model,RSC-derived photoreceptors can partially restore light response,indicating that those RSC-derived photoreceptors are functional.Finally,there is no evidence for tumor formation in the photoreceptor-transplanted eyes.Therefore,this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  17. Patterned electrical stimulation of primate retina for the development of retinal prostheses


    Epiretinal prostheses are designed to restore vision to people blinded by retinal degenerations, using electrical stimulation with an array of electrodes implanted on the surface of the retina to convey artificial visual signals to the brain. Current clinical prostheses provide limited visual function, in part because the activity that they generate is different from natural retinal responses to visual stimuli. An ideal retinal prosthesis would stimulate the retinal ganglion cells (RGCs) in a...


    Xiao Wang; Shi-xing Hu; Wei Li; Shao-chun Lin


    Objective To investigate the role of Caspase-3 in retinal damage caused by light exposure in rats.Methods Light injury to retina was induced by persistent exposure to illumination (intensity; 30000±50 lux) of operating microscope for 30 minutes in the right eyes of Sprague-Dawley rats. The pathological changes of retina were observed under optical and electron microscopies at different time points, which were 6 hours, 1,3,7,and 15 days after the light exposure. Apoptosis of retinal cells was analyzed by flow cytometry. The activity of Caspase-3 was evaluated by using the Caspase-3 assay kit. At the same time, the expression of Caspase-3 protease was determined with Western blot analysis.Results The examination results of optical and transmission electron microscopes showed that edema of inner and outer segments of the retina, espectially the chondriosome inside the inner segment, became obvious 6 hours after the light exposure. The change was deteriorated along with the increasing time. The structures of the discoidal valve dissociated in the outer segment simultaneously. Disorderly arranged nuclei, karyopycnosis, and thinning in the outer nuclear layer were observed. The retinal pogment epithelium almost disappeared during the later stage. The staining results of Annexin-V combined with PI demonstrated that the proportion of apoptotic cells increased with time. The proportion between 7th day (82.7%) and 15th day (80.4%), however, showed no significant difference. Caspase-3 became remarkably active with the lapse of time, which increased from 0.02 at 6th hour to the peak of 9.8 at 7th day before it started to descend. The Western blot detected a expression of the active form of Caspase-3 at 7th day and 15th day.Conclusion Apoptosis of photoreceptor cells is markedly involved in the light damage and Caspase-3 protease may play an important role in the apoptotic process of the retina after light exposure in rats.

  19. Effect of increased oxygen tension on flicker-induced vasodilatation in the human retina.

    Palkovits, Stefan; Told, Reinhard; Boltz, Agnes; Schmidl, Doreen; Popa Cherecheanu, Alina; Schmetterer, Leopold; Garhöfer, Gerhard


    In the retina, blood flow and neural activity are tightly coupled. Stimulation of the retina with flickering light is accompanied by an increase in blood flow. The current study seeks to investigate whether an increase in oxygen tension modulates flicker (FL)-induced vasodilatation in the human retina. A total of 52 healthy volunteers were included. Via a breathing mask, 100% oxygen (O(2)) was administered in one, a mixture of 8% carbon dioxide and 92% oxygen (C/O) in a second cohort. Retinal vessel diameters were measured with a Vessel Analyzer and FL responses were assessed before and during the breathing periods. At baseline, FL stimulation increased retinal vessel diameters by +3.7±2.3% in arteries and by +5.1±3.7% in veins. Breathing of C/O led to a decrease in arterial (-9.0±6.9%) and venous (-11.3±5.9%) vessel calibers. Flicker response was increased to 5.7±2.5% in arteries and to 8.6±4.1% in veins. Breathing of pure O2 induced a vasoconstriction of vessel diameters by -14.0±5.3% in arteries and -18.4±7.0% in veins and increased FL responses in arteries (+6.2±2.8%) and veins (+7.2±3.1%). Systemic hyperoxia increases FL-induced retinal vasodilatation in the retina. The mechanism by which oxygen modulates the hyperemic response to FL stimulation remains to be elucidated.

  20. Patterning the Retina of Drosophila Melanogaster for Color and Polarized Light Vision

    Wernet, Mathias F.


    Across the animal kingdom, specialized sensory epithelia are used for photoreception, allowing individuals to interact with their environment based on visual cues. Generally, neuronal photoreceptor cells (PRs) are organized in the retina, a specialized part of body tissue exposed to the outside world, and transform the energy of incoming electromagnetic radiation into neuronal excitation. This process depends on the large family of opsin proteins which are required in PRs of all animal specie...

  1. Edge Detection Model Based on Involuntary Eye Movements of the Eye-Retina System

    András Róka


    Full Text Available Traditional edge-detection algorithms in image processing typically convolute afilter operator and the input image, and then map overlapping input image regions tooutput signals. Convolution also serves as a basis in biologically inspired (Sobel, Laplace,Canny algorithms. Recent results in cognitive retinal research have shown that ganglioncell receptive fields cover the mammalian retina in a mosaic arrangement, withinsignificant amounts of overlap in the central fovea. This means that the biologicalrelevance of traditional and widely adapted edge-detection algorithms with convolutionbasedoverlapping operator architectures has been disproved. However, using traditionalfilters with non-overlapping operator architectures leads to considerable losses in contourinformation. This paper introduces a novel, tremor-based retina model and edge-detectionalgorithm that reconciles these differences between the physiology of the retina and theoverlapping architectures used by today's widely adapted algorithms. The algorithm takesinto consideration data convergence, as well as the dynamic properties of the retina, byincorporating a model of involuntary eye tremors and the impulse responses of ganglioncells. Based on the evaluation of the model, two hypotheses are formulated on the highlydebated role of involuntary eye tremors: 1 The role of involuntary eye tremors hasinformation theoretical implications 2 From an information processing point of view, thefunctional role of involuntary eye-movements extends to more than just the maintenance ofaction potentials. Involuntary eye-movements may be responsible for the compensation ofinformation losses caused by a non-overlapping receptive field architecture. In support ofthese hypotheses, the article provides a detailed analysis of the model's biologicalrelevance, along with numerical simulations and a hardware implementation.

  2. Very long-chain fatty acids support synaptic structure and function in the mammalian retina

    Hopiavuori Blake R.


    Full Text Available Elongation of Very Long chain fatty acids-like 4 (ELOVL4 is a fatty acid elongase responsible for the biosynthesis of very long chain (VLC; ≥ C26 fatty acids in the retina, brain, skin, Meibomian gland, and testes. Heterozygous inheritance of mutant ELOVL4 causes juvenile macular degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3. Retinal photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs, which have been shown by our group and others to be necessary for the survival of rod photoreceptors. Our group performed a series of studies using mice conditionally depleted of retinal Elovl4 (KO aimed at understanding the role of VLC-PUFAs in long-term retinal health and function, focusing on the role of these fatty acids in mediating synaptic function between the photoreceptors and the rest of the neural retina. The absence of VLC-PUFA from the retina of KO mice resulted in a marked decrease in retinal b-wave responses of the electroretinogram as well as a decrease in the amplitude of the oscillatory potentials mediated by the neural retina. Although there were no measureable differences between KO and wild type (WT mice in either pre-synaptic rod calcium channel function or post-synaptic bipolar cell glutamate receptor responses, ultrastructural analysis revealed a marked decrease in the diameter of synaptic vesicles in rod terminals. Recent quantification suggests that this decrease in synaptic vesicle size due to the absence of VLC-PUFAs in KO mice, and the consequent decrease in glutamate content, could account for the decrease in b-wave response amplitudes that were previously measured in these animals.

  3. Transdifferentiation and survival of neural retina cells in relation to illumination.

    Pritchard, D J


    Cultures of chicken embryo neural retina cells were exposed to light of different intensities and colours, in order to identify the wavelengths that promote cell degeneration and transdifferentiation into pigment epithelium. Blue and green light caused cell death; blue, green and yellow light enhanced transdifferentiation; red light had no effect. The relevance of these findings to retinal degeneration in man and the possible mediation of rhodopsin, riboflavin and other chromophores are discussed.

  4. Descolamento de retina seroso em paraganglioma: relato de caso Serous retinal detachment in paraganglioma: case report

    Oscar Villas Boas


    Full Text Available Os autores descrevem um caso de uma paciente gestante com hipertensão arterial resistente ao tratamento e descolamento seroso bilateral de retina. Confirmou-se, pelo exame anátomo-patológico, ser um paraganglioma.The authors describe a case of a pregnant patient with arterial hypertension that resists to the treatment and retinal bilateral serous detachment. It was confirmed to be a paraganglioma by anatomicopathological examination.

  5. Role of the nucleolus in neurodegenerative diseases with particular reference to the retina: a review.

    Sia, Paul I; Wood, John Pm; Chidlow, Glyn; Sharma, Shiwani; Craig, Jamie; Casson, Robert J


    The nucleolus has emerged as a key regulator of cellular growth and the response to stress, in addition to its traditionally understood function in ribosome biogenesis. The association between nucleolar function and neurodegenerative disease is increasingly being explored. There is also recent evidence indicating that the nucleolus may well be crucial in the development of the eye. In this present review, the role of the nucleolus in retinal development as well as in neurodegeneration with an emphasis on the retina is discussed.

  6. Unidirectional photoreceptor-to-Muller glia coupling and unique K+ channel expression in Caiman retina.

    Astrid Zayas-Santiago

    Full Text Available BACKGROUND: Müller cells, the principal glial cells of the vertebrate retina, are fundamental for the maintenance and function of neuronal cells. In most vertebrates, including humans, Müller cells abundantly express Kir4.1 inwardly rectifying potassium channels responsible for hyperpolarized membrane potential and for various vital functions such as potassium buffering and glutamate clearance; inter-species differences in Kir4.1 expression were, however, observed. Localization and function of potassium channels in Müller cells from the retina of crocodiles remain, hitherto, unknown. METHODS: We studied retinae of the Spectacled caiman (Caiman crocodilus fuscus, endowed with both diurnal and nocturnal vision, by (i immunohistochemistry, (ii whole-cell voltage-clamp, and (iii fluorescent dye tracing to investigate K+ channel distribution and glia-to-neuron communications. RESULTS: Immunohistochemistry revealed that caiman Müller cells, similarly to other vertebrates, express vimentin, GFAP, S100β, and glutamine synthetase. In contrast, Kir4.1 channel protein was not found in Müller cells but was localized in photoreceptor cells. Instead, 2P-domain TASK-1 channels were expressed in Müller cells. Electrophysiological properties of enzymatically dissociated Müller cells without photoreceptors and isolated Müller cells with adhering photoreceptors were significantly different. This suggests ion coupling between Müller cells and photoreceptors in the caiman retina. Sulforhodamine-B injected into cones permeated to adhering Müller cells thus revealing a uni-directional dye coupling. CONCLUSION: Our data indicate that caiman Müller glial cells are unique among vertebrates studied so far by predominantly expressing TASK-1 rather than Kir4.1 K+ channels and by bi-directional ion and uni-directional dye coupling to photoreceptor cells. This coupling may play an important role in specific glia-neuron signaling pathways and in a new type of K

  7. Eye enucleation and regeneration of neural retina in axolotl larvae (Ambystoma mexicanum).

    Yew, D T


    The eyes of Axolotl larvae were enucleated at stages 30 and 37. Animals with single dorsomedian eyes resulted in the first case (i.e. stage 30). When a piece of pigment epithelium was re-implanted into stage 37 animals at the site of the lesion, limited regeneration was observed when the implant formed a vesicle, but, when the pigment epithelium remained "open" regeneration of the neural retina was extensive. The possible resons for this difference was discussed.

  8. Effects Of Primary Blast Overpressure On Retina And Optic Tract In Rats

    James eDemar


    Full Text Available Blast has been the leading cause of injury, particularly traumatic brain injury and visual system injury, in combat operations in Iraq and Afghanistan. We determined the effect of shock tube-generated primary blast on retinal electrophysiology and on retinal and brain optic tract histopathology in a rat model.The amplitude of a- and b- waves on the electroretinogram (ERG for both right and left eyes were measured prior to a battlefield-simulation Friedlander-type blast wave and on 1, 7, and 14 days thereafter. Histopathologic findings of the right and left retina and the right and left optic tracts (2.8 mm post-optic chiasm were evaluated 14 days after the blast.For two experiments in which the right eye was oriented to the blast, the amplitude of ERG a- and b-waves at 7 days post-blast on the right side but not on the left side was diminished compared to that of sham animals (P=0.005-0.01 Histopathologic injury scores at 14 days post-blast for the right retina but not the left retina were higher than for sham animals (P=0.01, and histopathologic injury scores at 14 days for both optic tracts were markedly higher than for shams (P < 0.0001. Exposure of one eye to a blast wave, comparable to that causing human injury, produced injury to the retina as determined by ERG and histopathology, and to both post-chiasmatic optic tracts as determined by histopathology. This model may be useful for analyzing the effect of therapeutic interventions on retinal damage due to primary blast waves.

  9. Circuit design for the retina-like image sensor based on space-variant lens array

    Gao, Hongxun; Hao, Qun; Jin, Xuefeng; Cao, Jie; Liu, Yue; Song, Yong; Fan, Fan


    Retina-like image sensor is based on the non-uniformity of the human eyes and the log-polar coordinate theory. It has advantages of high-quality data compression and redundant information elimination. However, retina-like image sensors based on the CMOS craft have drawbacks such as high cost, low sensitivity and signal outputting efficiency and updating inconvenience. Therefore, this paper proposes a retina-like image sensor based on space-variant lens array, focusing on the circuit design to provide circuit support to the whole system. The circuit includes the following parts: (1) A photo-detector array with a lens array to convert optical signals to electrical signals; (2) a strobe circuit for time-gating of the pixels and parallel paths for high-speed transmission of the data; (3) a high-precision digital potentiometer for the I-V conversion, ratio normalization and sensitivity adjustment, a programmable gain amplifier for automatic generation control(AGC), and a A/D converter for the A/D conversion in every path; (4) the digital data is displayed on LCD and stored temporarily in DDR2 SDRAM; (5) a USB port to transfer the data to PC; (6) the whole system is controlled by FPGA. This circuit has advantages as lower cost, larger pixels, updating convenience and higher signal outputting efficiency. Experiments have proved that the grayscale output of every pixel basically matches the target and a non-uniform image of the target is ideally achieved in real time. The circuit can provide adequate technical support to retina-like image sensors based on space-variant lens array.

  10. Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina

    Natsuyo Hata


    Full Text Available Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1, SAPK/ERK kinase 1 (SEK1 and c-Jun N-terminal kinase (JNK is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

  11. Functional aspects of the somatostatinergic system in the retina and the potential therapeutic role of somatostatin in retinal disease

    Casini, G.; Catalani, E.; M. Dal Monte; bagnoli, P


    The somatostatinergic system of the retina has been investigated in a variety of studies. A considerable amount of experimental evidence is available concerning the patterns of expression of somatostatin (SRIF) and its receptors in vertebrate retinas. However the functional roles of this peptidergic system in retinal physiology are far from being elucidated. Nonetheless, data have been provided concerning the regulatory action of SRIF on the excitability of...

  12. Type-1, but Not Type-5, Metabotropic Glutamate Receptors are Coupled to Polyphosphoinositide Hydrolysis in the Retina.

    Romano, Maria Rosaria; Di Menna, Luisa; Scarselli, Pamela; Mascio, Giada; Madonna, Michele; Notartomaso, Serena; Puliti, Aldamaria; Bruno, Valeria; Battaglia, Giuseppe; Nicoletti, Ferdinando


    mGlu1 and mGlu5 metabotropic glutamate receptors are expressed in the vertebrate retina, and are co-localized in some retinal neurons. It is believed that both receptors are coupled to polyphosphoinositide (PI) hydrolysis in the retina and their function may diverge in some cells because of a differential engagement of downstream signaling molecules. Here, we show that it is only the mGlu1 receptor that is coupled to PI hydrolysis in the retina. We used either bovine retinal slices or intact mouse retinas challenged with the mixed mGlu1/5 receptor agonist, DHPG. In both models, DHPG-stimulated PI hydrolysis was abrogated by the selective mGlu1 receptor antagonist, JNJ16259685, but was insensitive to the mGlu5 receptor antagonist, MPEP. In addition, the PI response to DHPG was unchanged in the retina of mGlu5(-/-) mice but was abolished in the retina of crv4 mice lacking mGlu1 receptors. Stimulation of the mitogen-activated protein kinase pathway by DHPG in intact mouse retinas were also entirely mediated by mGlu1 receptors. Our data provide the first example of a tissue in which a biochemically detectable PI response is mediated by mGlu1, but not mGlu5, receptors. Hence, bovine retinal slices might be used as a model for the functional screening of mGlu1 receptor ligands. In addition, the mGlu1 receptor caters the potential as a drug target in the experimental treatment of degenerative disorders of the retina.

  13. Actin-Cytoskeleton- and Rock-Mediated INM Are Required for Photoreceptor Regeneration in the Adult Zebrafish Retina

    Lahne, Manuela; Li, Jingling; Marton, Rebecca M.; Hyde, David R.


    Loss of retinal neurons in adult zebrafish (Danio rerio) induces a robust regenerative response mediated by the reentry of the resident Müller glia into the cell cycle. Upon initiating Müller glia proliferation, their nuclei migrate along the apicobasal axis of the retina in phase with the cell cycle in a process termed interkinetic nuclear migration (INM). We examined the mechanisms governing this cellular process and explored its function in regenerating the adult zebrafish retina. Live-cel...

  14. Flash responses of mouse rod photoreceptors in the isolated retina and corneal electroretinogram: comparison of gain and kinetics.

    Heikkinen, Hanna; Vinberg, Frans; Pitkänen, Marja; Kommonen, Bertel; Koskelainen, Ari


    To examine the amplification and kinetics of murine rod photoresponses by recording ERG flash responses in vivo and ex vivo from the same retina. We also aimed to evaluate the two available methods for isolating the rod signal from the ERG flash response, that is, pharmacology and paired flash method on the isolated retina. Dark-adapted ERG responses to full-field flashes of green light were recorded from anesthetized (ketamine/xylazine) C57BL/6N mice. ERG flash responses to homogenous light stimuli arriving from the photoreceptor side were then recorded transretinally from the same retinas, isolated and perfused with Ringer's or Ames' solution at 37°C. The responses were analyzed to determine the a-wave kinetics as well as the estimated flash sensitivity and kinetics of the full rod responses derived with the paired flash protocol. The analysis was complemented with pharmacologic blockade of glutamatergic transmission in the isolated retina. The a-waves were of comparable size, sensitivity and kinetics in vivo and in the isolated retina, but the onset of the b-wave was delayed in the isolated retina. The Lamb-Pugh activation constants determined for the a-waves were similar in both preparations. The kinetics of the derived photoreceptor responses were similar in both conditions, although the responses were consistently slightly slower ex vivo. This was not explicable as a direct effect of ketamine or xylazine on the photoreceptors or as their indirect effect through hyperglycemia, as tested on the isolated retina. Through comparison to the corneal ERG, the transretinal ERG is a valuable tool for assaying the physiologic state of isolated retinal tissue. The rod photoreceptor responses of the intact isolated retina correspond well to those recorded in vivo. The origin of their faster kinetics compared to single cell recordings remains to be determined.

  15. Expression of peroxisome proliferator-activated receptor γ in rat retina during development

    Ju-Ming Zhu


    Full Text Available AIM: To evaluate the spatiotemporal expression pattern of PPARγ in embryonic and early postnatal stages of rat retina. METHODS: Fetal rats were collected at 13-18d of gestation (GD from pregnant females and postnatal rats at 1d (P1 and 5d (P5 after birth were also used. We used RT-PCR to detect PPARγ mRNA and immunohistochemical to observe PPARγ protein. And at last, we chose HE staining showed the structural changes of rat retina during development. RESULTS: RT-PCR analysis showed that PPARγ mRNA was expressed as early as GD13 and gradually decreased as maturation continued. However, the PPARγ gene expression significantly increased after birth, especially in P5. Immunohistochemical analysis showed PPARγ protein was expressed throughout the retinal neuroepithelium at GD13 and GD14, and then decreased during late embryogenesis but remained relatively high in the predicted ganglion cell zone. During postnatal development, PPARγ protein was remarkably increased and the positive signals were mainly located in nerve fiber layer (NFL, ganglion cell layer (GCL and outer layers of the retina. CONCLUSION: The spatiotemporal changes of PPARγ expression demonstrated that PPARγ might play a role in regulating the differentiation and maturation of retinal cells.

  16. Transforming growth factor-beta (TGF-beta) and programmed cell death in the vertebrate retina.

    Duenker, Nicole


    Programmed cell death (PCD) is a precisely regulated phenomenon essential for the homeostasis of multicellular organisms. Developmental systems, particularly the nervous system, have provided key observations supporting the physiological role of PCD. We have recently shown that transforming growth factor-beta (TGF-beta) plays an important role in mediating ontogenetic PCD in the nervous system. As part of the central nervous system the developing retina serves as an ideal model system for investigating apoptotic processes during neurogenesis in vivo as it is easily accessible experimentally and less complex due to its limited number of different neurons. This review summarizes data indicating a pivotal role of TGF-beta in mediating PCD in the vertebrate retina. The following topics are discussed: expression of TGF-beta isoforms and receptors in the vertebrate retina, the TGF-beta signaling pathway, functions and molecular mechanisms of PCD in the nervous system, TGF-beta-mediated retinal apoptosis in vitro and in vivo, and interactions of TGF-beta with other pro- and anti-apoptotic factors.

  17. Folate antagonist, methotrexate induces neuronal differentiation of human embryonic stem cells transplanted into nude mouse retina.

    Hara, Akira; Taguchi, Ayako; Aoki, Hitomi; Hatano, Yuichiro; Niwa, Masayuki; Yamada, Yasuhiro; Kunisada, Takahiro


    Transplanted embryonic stem (ES) cells can be integrated into the retinas of adult mice as well-differentiated neuroretinal cells. However, the transplanted ES cells also have a tumorigenic activity as they have the ability for multipotent differentiation to various types of tissues. In the present study, human ES (hES) cells were transplanted into adult nude mouse retinas by intravitreal injections 20 h after intravitreal N-methyl-D-aspartate (NMDA) administration. After the transplantation of hES cells, the folate antagonist, methotrexate (MTX) was administrated in order to control the differentiation of the transplanted hES cells. Neuronal differentiation and teratogenic potential of hES cells were examined immunohistochemically 5 weeks after transplantation. The proliferative activity of transplanted cells was determined by both the mitotic index and the Ki-67 proliferative index. Disappearance of Oct-4-positive hES cells showing undifferentiated morphology was observed after intraperitoneal MTX treatment daily, for 15 days. Decreased mitotic and Ki-67 proliferative indices, and increased neuronal differentiation were detected in the surviving hES cells after the MTX treatment. These results suggest two important effects of intraperitoneal MTX treatment for hES cells transplanted into nude mouse retina: (1) MTX treatment following transplantation induces neuronal differentiation, and (2) MTX decreases proliferative activity and tumorigenic potential.

  18. β-Catenin inactivation is a pre-requisite for chick retina regeneration.

    Jie Zhu

    Full Text Available In the present study we explored the role of β-catenin in mediating chick retina regeneration. The chick can regenerate its retina by activating stem/progenitor cells present in the ciliary margin (CM of the eye or via transdifferentiation of the retinal pigmented epithelium (RPE. Both modes require fibroblast growth factor 2 (FGF2. We observed, by immunohistochemistry, dynamic changes of nuclear β-catenin in the CM and RPE after injury (retinectomy. β-Catenin nuclear accumulation was transiently lost in cells of the CM in response to injury alone, while the loss of nuclear β-catenin was maintained as long as FGF2 was present. However, nuclear β-catenin positive cells remained in the RPE in response to injury and were BrdU-/p27+, suggesting that nuclear β-catenin prevents those cells from entering the cell cycle. If FGF2 is present, the RPE undergoes dedifferentiation and proliferation concomitant with loss of nuclear β-catenin. Moreover, retinectomy followed by disruption of active β-catenin by using a signaling inhibitor (XAV939 or over-expressing a dominant negative form of Lef-1 induces regeneration from both the CM and RPE in the absence of FGF2. Our results imply that β-catenin protects cells of the CM and RPE from entering the cell cycle in the developing eye, and specifically for the RPE during injury. Thus inactivation of β-catenin is a pre-requisite for chick retina regeneration.

  19. The in vitro protective effect of alpha-tocopherol on oxidative injury in the dog retina.

    Zapata, G L; Guajardo, M H; Terrasa, A M


    Oxidative stress is a risk factor for eye diseases. Free radicals elicited during the inflammatory process often lead to oxidative damage of lipids (lipid peroxidation). The retina is highly vulnerable because of its high content of polyunsaturated fatty acids (PUFAs). The aim of this study was to investigate in vitro the effect of alpha-tocopherol on the Fe(2+)-ascorbate induced lipid peroxidation in the canine retina. Lipid peroxidation of retinal homogenates was carried out with and without the addition of alpha-tocopherol and monitored both by chemiluminescence and production of thiobarbituric acid reactive substances (TBARS). Total chemiluminescence counts per minute was lower in those homogenates pre-incubated with alpha-tocopherol. Thus, with 1 micromol alpha-tocopherol/mg of protein, 100% inhibition of chemiluminescence and a decrease of TBARS content from 20.46+/-0.85 to 2.62+/-2.77 nmol/mg protein were observed. Simultaneously, changes produced by oxidative stress were noted in the fatty acid composition of retinal lipids. Docosahexaenoic acid was decreased from 14.33+/-2.32% to 1.84+/-0.14% after peroxidation, but this fatty acid remained unaltered in the presence of 1 micromol alpha-tocopherol. These results show that under these experimental conditions, alpha-tocopherol may act as anti-oxidant protecting retinal membranes from deleterious effects. Further studies are required to assess its use in free radical generating conditions affecting the canine