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Sample records for human retinal imagery

  1. Detection of Anatomic Structures in Human Retinal Imagery

    Energy Technology Data Exchange (ETDEWEB)

    Tobin Jr, Kenneth William [ORNL; Chaum, Edward [ORNL; Muthusamy Govindasamy, Vijaya Priya [ORNL; Karnowski, Thomas Paul [ORNL

    2007-01-01

    The widespread availability of electronic imaging devices throughout the medical community is leading to a growing body of research on image processing and analysis to diagnose retinal disease such as diabetic retinopathy (DR). Productive computer-based screening of large, at-risk populations at low cost requires robust, automated image analysis. In this paper we present results for the automatic detection of the optic nerve and localization of the macula using digital red-free fundus photography. Our method relies on the accurate segmentation of the vasculature of the retina followed by the determination of spatial features describing the density,average thickness, and average orientation of the vasculature in relation to the position of the optic nerve. Localization of the macula follows using knowledge of the optic nerve location to detect the horizontal raphe of the retina using a geometric model of the vasculature. We report 90.4% detection performance for the optic nerve and 92.5% localization performance for the macula for red-free fundus images representing a population of 345 images corresponding to 269 patients with 18 different pathologies associated with DR and other common retinal diseases such as age-related macular degeneration.

  2. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism. Methods: After exposure to hypoxia (1 % O2) for 5 days, cell proliferation and cell cycle of HREC were ...

  3. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

    OpenAIRE

    Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komáromy, András M.; Hauswirth, William W.; Aguirre, Gustavo D.

    2013-01-01

    The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study ...

  4. Production of iPS-Derived Human Retinal Organoids for Use in Transgene Expression Assays

    NARCIS (Netherlands)

    Quinn, Peter M; Buck, Thilo M; Ohonin, Charlotte; Mikkers, Harald M M; Wijnholds, J.

    2018-01-01

    In vitro retinal organoid modeling from human pluripotent stem cells is becoming more common place in many ophthalmic laboratories worldwide. These organoids mimic human retinogenesis through formation of organized layered retinal structures that display markers for typical retinal cell types.

  5. Human bone marrow mesenchymal stem cells for retinal vascular injury.

    Science.gov (United States)

    Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

    2017-09-01

    To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley

  6. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

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    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  7. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid.

    Science.gov (United States)

    Sanie-Jahromi, Fatemeh; Ahmadieh, Hamid; Soheili, Zahra-Soheila; Davari, Maliheh; Ghaderi, Shima; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Deezagi, Abdolkhalegh; Pakravesh, Jalil; Bagheri, Abouzar

    2012-04-10

    Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers) during treatment of human retinal pigment epithelium (RPE) cells with amniotic fluid (AF), RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1) confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  8. Efficacy and Safety of Human Retinal Progenitor Cells

    Science.gov (United States)

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  9. EFFECTUAL HUMAN AUTHENTICATION FOR CRITICAL SECURITY APPLICATIONS USING RETINAL IMAGES

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    L. Latha

    2010-11-01

    Full Text Available A robust method of human authentication based on the retinal blood vessel pattern is presented in this paper. This method entails a segmentation process to identify retinal blood vessel pattern, template generation consisting of the bifurcation points in the retina and matching of the intersection points in the template patterns. The number of matched blood vessel intersection points between the two patterns compared is used as a measure of similarity. As Liveness detection is a highly desirable anti-spoofing measure in biometric authentication, it is ensured while acquiring retinal images in realtime. The validity of our approach is verified with experimental results obtained from 603 comparisons made using 303 retinal images from three different publicly available databases, namely DRIVE, VARIA and STARE. We found that the proposed retinal recognition method gives 100%, 96.3% and 91.1% recognition rates respectively for the above databases. To the best of our knowledge, this is the first work that uses a large number of retinal images from different retinal databases for the authentication purpose.

  10. Characterization of the optic disc in retinal imagery using a probabilistic approach

    Science.gov (United States)

    Tobin, Kenneth W., Jr.; Chaum, Edward; Govindasamy, V. P.; Karnowski, Thomas P.; Sezer, Omer

    2006-03-01

    The application of computer based image analysis to the diagnosis of retinal disease is rapidly becoming a reality due to the broad-based acceptance of electronic imaging devices throughout the medical community and through the collection and accumulation of large patient histories in picture archiving and communications systems. Advances in the imaging of ocular anatomy and pathology can now provide data to diagnose and quantify specific diseases such as diabetic retinopathy (DR). Visual disability and blindness have a profound socioeconomic impact upon the diabetic population and DR is the leading cause of new blindness in working-age adults in the industrialized world. To reduce the impact of diabetes on vision loss, robust automation is required to achieve productive computer-based screening of large at-risk populations at lower cost. Through this research we are developing automation methods for locating and characterizing important structures in the human retina such as the vascular arcades, optic nerve, macula, and lesions. In this paper we present results for the automatic detection of the optic nerve using digital red-free fundus photography. Our method relies on the accurate segmentation of the vasculature of the retina along with spatial probability distributions describing the luminance across the retina and the density, average thickness, and average orientation of the vasculature in relation to the position of the optic nerve. With these features and other prior knowledge, we predict the location of the optic nerve in the retina using a two-class, Bayesian classifier. We report 81% detection performance on a broad range of red-free fundus images representing a population of over 345 patients with 19 different pathologies associated with DR.

  11. Distributions of elements in the human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Ulshafer, R.J.; Allen, C.B.; Rubin, M.L.

    1990-01-01

    Distributions of elements above the atomic number of sodium were mapped in the retinal pigment epithelia of eight human eyes. X-ray energy spectra and maps were collected from cryofixed, freeze-dried, and epoxy-embedded tissues using energy-dispersive x-ray microanalysis. All eyes had high concentrations of phosphorus in the nuclei of retinal pigment epithelial cells. Melanosomes were rich in sulfur, zinc, calcium, and iron. Lipofuscin and cytoplasm contained only phosphorus and sulfur in detectable amounts. Drusen, when present, contained phosphorus and calcium. Six eyes had a prominent aluminum peak recorded from melanosomes, nuclei, and Bruch's membrane. In one pair of 90-year-old eyes, small, electron-dense deposits surrounded many melanosomes and contained mercury and selenium. Retinal pigment epithelial melanosomes may bind and accumulate metals and other potentially toxic ions over time, preventing them from reaching the neural retina

  12. Zinc uptake in vitro by human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Newsome, D.A.; Rothman, R.J.

    1987-01-01

    Zinc, an essential trace element, is present in unusually high concentrations in the chorioretinal complex relative to most other tissues. Because little has been known about the interactions between the retinal pigment epithelium and free or protein-associated zinc, we studied 65 Zn uptake by human retinal pigment epithelium in vitro. When monolayers were exposed to differing concentrations from 0 to 30 microM 65 Zn in Dulbecco's modified Eagle's medium with 5.4 gm/l glucose at 37 degrees C and 4 degrees C, we observed a temperature-dependent saturable accumulation of the radiolabel. With 15 microM 65 Zn, we saw a biphasic pattern of uptake with a rapid first phase and a slower second phase over 120 min. Uptake of 65 Zn was inhibited by iodacetate and cold, and reduced approximately 50% by the addition of 2% albumin to the labelling medium. Neither ouabain nor 2-deoxyglucose inhibited uptake. Cells previously exposed to 65 Zn retained approximately 70% of accumulated 65 Zn 60 min after being changed to radiolabel-free medium. Following removal of cells from the extracellular matrix adherent to the dish bottom, a variable amount of nonspecific binding of 65 Zn to the residual matrix was demonstrated. These observations are consistent with a facilitated type of transport and demonstrate the ability of human retinal pigment epithelium in vitro to accumulate and retain zinc

  13. Functional annotation of the human retinal pigment epithelium transcriptome

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    Gorgels Theo GMF

    2009-04-01

    Full Text Available Abstract Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE, the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years were laser dissected and used for 22k microarray studies (Agilent technologies. Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194 expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776 genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194 of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the

  14. Melanopsin expressing human retinal ganglion cells

    DEFF Research Database (Denmark)

    Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen

    2017-01-01

    microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1...

  15. Melanopsin-expressing retinal ganglion cells: implications for human diseases

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Hannibal, Jens

    2011-01-01

    In the last decade, there was the seminal discovery of melanopsin-expressing retinal ganglion cells (mRGCs) as a new class of photoreceptors that subserve the photoentrainment of circadian rhythms and other non-image forming functions of the eye. Since then, there has been a growing research...... interest on these cells, mainly focused on animal models. Only recently, a few studies have started to address the relevance of the mRGC system in humans and related diseases. We recently discovered that mRGCs resist neurodegeneration in two inherited mitochondrial disorders that cause blindness, i...

  16. High-speed adaptive optics line scan confocal retinal imaging for human eye.

    Science.gov (United States)

    Lu, Jing; Gu, Boyu; Wang, Xiaolin; Zhang, Yuhua

    2017-01-01

    Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye's optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss.

  17. Human amniotic fluid promotes retinal pigmented epithelial cells' trans-differentiation into rod photoreceptors and retinal ganglion cells.

    Science.gov (United States)

    Ghaderi, Shima; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Davari, Maliheh; Jahromi, Fatemeh Sanie; Samie, Shahram; Rezaie-Kanavi, Mozhgan; Pakravesh, Jalil; Deezagi, Abdolkhalegh

    2011-09-01

    To evaluate the effect of human amniotic fluid (HAF) on retinal pigmented epithelial cells growth and trans-differentiation into retinal neurons, retinal pigmented epithelium (RPE) cells were isolated from neonatal human cadaver eye globes and cultured in Dulbecco's modified Eagle's medium-F12 supplemented with 10% fetal bovine serum (FBS). Confluent monolayer cultures were trypsinized and passaged using FBS-containing or HAF-containing media. Amniotic fluid samples were received from pregnant women in the first trimester of gestation. Cell proliferation and death enzyme-linked immunosorbent assays were performed to assess the effect of HAF on RPE cell growth. Trans-differentiation into rod photoreceptors and retinal ganglion cells was also studied using immunocytochemistry and real-time polymerase chain reaction techniques. Primary cultures of RPE cells were successfully established under FBS-containing or HAF-containing media leading to rapid cell growth and proliferation. When RPE cells were moved to in vitro culture system, they began to lose their differentiation markers such as pigmentation and RPE65 marker and trans-differentiated neural-like cells followed by spheroid colonies pertaining to stem/progenitor cells were morphologically detected. Immunocytochemistry (ICC) analysis of HAF-treated cultures showed a considerable expression of Rhodopsin gene (30% Rhodopsin-positive cells) indicating trans-differentiation of RPE cells to rod photoreceptors. Real-time polymerase chain reaction revealed an HAF-dose-dependant expression of Thy-1 gene (RGC marker) and significant promoting effect of HAF on RGCs generation. The data presented here suggest that HAF possesses invaluable stimulatory effect on RPE cells growth and trans-differentiation into retinal neurons. It can be regarded as a newly introduced enriched supplement in serum-free kinds of media used in neuro-retinal regeneration studies.

  18. Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy

    NARCIS (Netherlands)

    van der Lelij, A.; Rothova, A.; Stilma, J. S.; Hoekzema, R.; Kijlstra, A.

    1990-01-01

    Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from

  19. Retinal and post-retinal contributions to the Quantum efficiency of the human eye revealed by electrical neuroimaging

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    Gibran eManasseh

    2013-11-01

    Full Text Available The retina is one of the best known quantum detectors with rods able to reliably respond to single photons. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values after discounting by retinal losses. One possibility is that there is a trade-off between the limited motor resources available to living systems and the excellent reliability of the visual photoreceptors. On this view, the limits to sensory thresholds are not set by the individual reliability of the receptors within each sensory modality (as often assumed but rather by the limited central processing and motor resources available to process the constant inflow of sensory information. To investigate this issue, we reproduced the classical experiment from Hetch aimed to determine the sensory threshold in human vision. We combined a careful physical control of the stimulus parameters with high temporal/spatial resolution recordings of EEG signals and behavioral variables over a relatively large sample of subjects (12. Contrarily to the idea that the limits to visual sensitivity are fully set by the statistical fluctuations in photon absorption on retinal photoreceptors we observed that the state of ongoing neural oscillations before any photon impinges the retina helps to determine if the responses of photoreceptors have access to central conscious processing. Our results suggest that motivational and attentional off-retinal mechanisms play a major role in reducing the QE efficiency of the human visual system when compared to the efficiency of isolated retinal photoreceptors. Yet, this mechanism might subserve adaptive behavior by enhancing the overall multisensory efficiency of the whole system composed by diverse reliable sensory modalities.

  20. Robust Differentiation of mRNA-Reprogrammed Human Induced Pluripotent Stem Cells Toward a Retinal Lineage.

    Science.gov (United States)

    Sridhar, Akshayalakshmi; Ohlemacher, Sarah K; Langer, Kirstin B; Meyer, Jason S

    2016-04-01

    The derivation of human induced pluripotent stem cells (hiPSCs) from patient-specific sources has allowed for the development of novel approaches to studies of human development and disease. However, traditional methods of generating hiPSCs involve the risks of genomic integration and potential constitutive expression of pluripotency factors and often exhibit low reprogramming efficiencies. The recent description of cellular reprogramming using synthetic mRNA molecules might eliminate these shortcomings; however, the ability of mRNA-reprogrammed hiPSCs to effectively give rise to retinal cell lineages has yet to be demonstrated. Thus, efforts were undertaken to test the ability and efficiency of mRNA-reprogrammed hiPSCs to yield retinal cell types in a directed, stepwise manner. hiPSCs were generated from human fibroblasts via mRNA reprogramming, with parallel cultures of isogenic human fibroblasts reprogrammed via retroviral delivery of reprogramming factors. New lines of mRNA-reprogrammed hiPSCs were established and were subsequently differentiated into a retinal fate using established protocols in a directed, stepwise fashion. The efficiency of retinal differentiation from these lines was compared with retroviral-derived cell lines at various stages of development. On differentiation, mRNA-reprogrammed hiPSCs were capable of robust differentiation to a retinal fate, including the derivation of photoreceptors and retinal ganglion cells, at efficiencies often equal to or greater than their retroviral-derived hiPSC counterparts. Thus, given that hiPSCs derived through mRNA-based reprogramming strategies offer numerous advantages owing to the lack of genomic integration or constitutive expression of pluripotency genes, such methods likely represent a promising new approach for retinal stem cell research, in particular, those for translational applications. In the current report, the ability to derive mRNA-reprogrammed human induced pluripotent stem cells (hi

  1. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    Science.gov (United States)

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-05-06

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. 2015 BMJ Publishing Group Ltd.

  2. Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Xue [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Wang, Ke, E-mail: wangke@jsinm.org [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Zhang, Kai [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Zhou, Fanfan [Faculty of Pharmacy, University of Sydney, New South Wales 2006 (Australia); Zhu, Ling [Save Sight Institute, University of Sydney, New South Wales 2000 (Australia)

    2016-10-15

    Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

  3. Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

    International Nuclear Information System (INIS)

    Zhu, Xue; Wang, Ke; Zhang, Kai; Zhou, Fanfan; Zhu, Ling

    2016-01-01

    Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

  4. Politics and Human Welfare: Retinitis Pigmentosa Patients in South Africa.

    Science.gov (United States)

    McKendrick, B. W.; Leketi, M.

    1990-01-01

    The study found that apartheid impacted the sociopsychological and physical circumstances of 12 African and 11 White people with retinitis pigmentosa in South Africa. Findings are discussed in terms of onset of condition, effects on subjects' lives, knowledge of social services, and needs unmet by existing services. (JDD)

  5. NUTRITION AND VASCULAR SUPPLY OF RETINAL GANGLION CELLS DURING HUMAN DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Paul eRutkowski

    2016-04-01

    Full Text Available Purpose. To review the roles of the different vascular beds nourishing the inner retina (retinal ganglion cells during normal development of the human eye and using our own tissue specimens to support our conclusions.Methods. An extensive search of the appropriate literature included PubMed, Google scholar, and numerous available textbooks. In addition, choroidal and retinal NADPH-diaphorase stained whole mount preparations were investigated.Results. The first critical interaction between vascular bed and retinal ganglion cell (RGC formation occurs in the 6th-8th month of gestation leading to a massive reduction of RGCs mainly in the peripheral retina. The first three years of age are characterized by an intense growth of the eyeball to near adult size. In the adult eye, the influence of the choroid on inner retinal nutrition was determined by examining the peripheral retinal watershed zones in more detail.Conclusion. This delicately balanced situation of retinal ganglion cell nutrition is described in the different regions of the eye, and a new graphic presentation is introduced to combine morphological measurements and clinical visual field data.

  6. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Delyfer

    Full Text Available BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.

  7. Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.

    Science.gov (United States)

    Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Zhang, Wei; Lanza, Robert; Lu, Shi-Jiang; Jonas, Jost B; Xu, Liang

    2017-09-01

    To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate-buffered saline (PBS). We examined the vasculature integrity in the mice with OIR, the blood-retina barrier in the rats with induced DR, and retinal thickness and retinal ganglion cell density in retina flat mounts of the rats with the retinal ischaemic-reperfusion retinopathy. In the OIR model, the study group versus control groups showed a significantly (p < 0.001) smaller retinal avascular area [5.1 ± 2.7%;n = 18 animals versus 12.2 ± 2.8% (PBS group; n = 10 animals) and versus 11.8 ± 3.7% (EC group; n = 8 animals)] and less retinal neovascularization [6.3 ± 2.5%;n = 18 versus 15.2 ± 6.3% (n = 10; PBS group) and versus 15.8 ± 3.3% (n = 8; EC group)]. On retinal flat mounts, hESC-HBs were integrated into damaged retinal vessels and stained positive for PECAM (CD31) as EC marker. In the DR model, the study group versus the EC control group showed a significantly (p = 0.001) better blood-retina barrier function as measured at 2 days after the intravitreal injections [study group: 20.2 ± 12.8 μl/(g × hr); n = 6; versus EC control group: 52.9 ± 9.9 μl/(g × hr; n = 6)]. In the retinal ischaemia-reperfusion model, the groups did not differ significantly in retinal thickness and retinal ganglion cell density at 2, 5 and 7 days after baseline. By integrating into

  8. Contacting co-culture of human retinal microvascular endothelial cells alters barrier function of human embryonic stem cell derived retinal pigment epithelial cells.

    Science.gov (United States)

    Skottman, H; Muranen, J; Lähdekorpi, H; Pajula, E; Mäkelä, K; Koivusalo, L; Koistinen, A; Uusitalo, H; Kaarniranta, K; Juuti-Uusitalo, K

    2017-10-01

    Here we evaluated the effects of human retinal microvascular endothelial cells (hREC) on mature human embryonic stem cell (hESC) derived retinal pigment epithelial (RPE) cells. The hESC-RPE cells (Regea08/017, Regea08/023 or Regea11/013) and hREC (ACBRI 181) were co-cultured on opposite sides of transparent membranes for up to six weeks. Thereafter barrier function, small molecule permeability, localization of RPE and endothelial cell marker proteins, cellular fine structure, and growth factor secretion of were evaluated. After co-culture, the RPE specific CRALBP and endothelial cell specific von Willebrand factor were appropriately localized. In addition, the general morphology, pigmentation, and fine structure of hESC-RPE cells were unaffected. Co-culture increased the barrier function of hESC-RPE cells, detected both with TEER measurements and cumulative permeability of FD4 - although the differences varied among the cell lines. Co-culturing significantly altered VEGF and PEDF secretion, but again the differences were cell line specific. The results of this study showed that co-culture with hREC affects hESC-RPE functionality. In addition, co-culture revealed drastic cell line specific differences, most notably in growth factor secretion. This model has the potential to be used as an in vitro outer blood-retinal barrier model for drug permeability testing. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Expression of Sirtuins in the Retinal Neurons of Mice, Rats, and Humans

    Directory of Open Access Journals (Sweden)

    Hongdou Luo

    2017-11-01

    Full Text Available Sirtuins are a class of histone deacetylases (HDACs that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7 that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas. Expression of all 7 Sirtuins was confirmed by Western blot and Real-Time PCR analysis in all three species. SIRT1 is highly expressed in mouse, rat, and human retinas, whereas SIRT2-7 expression was relatively lower in human retinas. Immunofluorescence was also used to examine the expression and localization of Sirtuins in rat retinal neurons. Importantly, we demonstrate a marked reduction of SIRT1 expression in aged retinal neurons as well as retinas injured by acute ischemia-reperfusion. On the other hand, none of the other Sirtuins exhibit any significant age-related changes in expression except for SIRT5, which was significantly higher in the retinas of adults compared to both young and aged rats. Our work presents the first composite analysis of Sirtuins in the retinal neurons of mice, rats, and humans, and suggests that increasing the expression and activity of SIRT1 may be beneficial for the treatment of glaucoma and other age-related eye dysfunction.

  10. Retinal images in the human eye with implanted intraocular lens

    Science.gov (United States)

    Zając, Marek; Siedlecki, Damian; Nowak, Jerzy

    2007-04-01

    A typical proceeding in cataract is based on the removal of opaque crystalline lens and inserting in its place the artificial intraocular lens (IOL). The quality of retinal image after such procedure depends, among others, on the parameters of the IOL, so the design of the implanted lens is of great importance. An appropriate choice of the IOL material, especially in relation to its biocompatibility, is often considered. However the parameter, which is often omitted during the IOL design is its chromatic aberration. In particular lack of its adequacy to the chromatic aberration of a crystalline lens may cause problems. In order to fit better chromatic aberration of the eye with implanted IOL to that of the healthy eye we propose a hybrid - refractive-diffractive IOL. It can be designed in such way that the total longitudinal chromatic aberration of an eye with implanted IOL equals the total longitudinal chromatic aberration of a healthy eye. In this study we compare the retinal image quality calculated numerically on the basis of the well known Liou-Brennan eye model with typical IOL implanted with that obtained if the IOL is done as hybrid (refractive-diffractive) design.

  11. Molecular Responses of Human Retinal Cells to Infection with Dengue Virus.

    Science.gov (United States)

    Carr, Jillian M; Ashander, Liam M; Calvert, Julie K; Ma, Yuefang; Aloia, Amanda; Bracho, Gustavo G; Chee, Soon-Phaik; Appukuttan, Binoy; Smith, Justine R

    2017-01-01

    Recent clinical reports indicate that infection with dengue virus (DENV) commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin- β 1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

  12. Molecular Responses of Human Retinal Cells to Infection with Dengue Virus

    Directory of Open Access Journals (Sweden)

    Jillian M. Carr

    2017-01-01

    Full Text Available Recent clinical reports indicate that infection with dengue virus (DENV commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin-β1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

  13. Human retinal pigment epithelial cell-induced apoptosis in activated T cells

    DEFF Research Database (Denmark)

    Jørgensen, A; Wiencke, A K; la Cour, M

    1998-01-01

    human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...... induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which...

  14. Human retinal pigment epithelial cell-induced apoptosis in activated T cells

    DEFF Research Database (Denmark)

    Jørgensen, A; Wiencke, A K; la Cour, M

    1998-01-01

    PURPOSE: The immune privilege of the eye has been thought to be dependent on physical barriers and absence of lymphatic vessels. However, the immune privilege may also involve active immunologic processes, as recent studies have indicated. The purpose of the present study was to investigate whether...... human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...

  15. Inner Retinal Oxygen Extraction Fraction in Response to Light Flicker Stimulation in Humans

    Science.gov (United States)

    Felder, Anthony E.; Wanek, Justin; Blair, Norman P.; Shahidi, Mahnaz

    2015-01-01

    Purpose Light flicker has been shown to stimulate retinal neural activity, increase blood flow, and alter inner retinal oxygen metabolism (MO2) and delivery (DO2). The purpose of the study was to determine the change in MO2 relative to DO2 due to light flicker stimulation in humans, as assessed by the inner retinal oxygen extraction fraction (OEF). Methods An optical imaging system, based on a modified slit lamp biomicroscope, was developed for simultaneous measurements of retinal vascular diameter (D) and oxygen saturation (SO2). Retinal images were acquired in 20 healthy subjects before and during light flicker stimulation. Arterial and venous D (DA and DV) and SO2 (SO2A and SO2V) were quantified within a circumpapillary region. Oxygen extraction fraction was defined as the ratio of MO2 to DO2 and was calculated as (SO2A − SO2V)/SO2A. Reproducibility of measurements was assessed. Results Coefficients of variation and intraclass correlation coefficients of repeated measurements were <5% and ≥0.83, respectively. During light flicker stimulation, DA, DV , and SO2V significantly increased (P ≤ 0.004). Oxygen extraction fraction was 0.37 ± 0.08 before light flicker and significantly decreased to 0.31 ± 0.07 during light flicker (P = 0.001). Conclusions Oxygen extraction fraction before and during light flicker stimulation is reported in human subjects for the first time. Oxygen extraction fraction decreased during light flicker stimulation, indicating the change in DO2 exceeded that of MO2. This technology is potentially useful for the detection of changes in OEF response to light flicker in physiological and pathological retinal conditions. PMID:26469748

  16. Poly(trimethylene carbonate) as an elastic biodegradable film for human embryonic stem cell-derived retinal pigment epithelial cells

    NARCIS (Netherlands)

    Sorkio, Anni; Haimi, Suvi; Verdoold, Vincent; Juuti-Uusitalo, Kati; Grijpma, Dirk; Skottman, Heli

    2017-01-01

    Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great

  17. Poly(trimethylene carbonate) as an elastic biodegradable film for human embryonic stem cell-derived retinal pigment epithelial cells

    NARCIS (Netherlands)

    Sorkio, Anni; Haimi, Suvi; Verdoold, Vincent; Juuti-Uusitalo, Kati; Grijpma, Dirk; Skottman, Heli

    Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great

  18. Portraying Urban Functional Zones by Coupling Remote Sensing Imagery and Human Sensing Data

    Directory of Open Access Journals (Sweden)

    Wei Tu

    2018-01-01

    Full Text Available Portraying urban functional zones provides useful insights into understanding complex urban systems and establishing rational urban planning. Although several studies have confirmed the efficacy of remote sensing imagery in urban studies, coupling remote sensing and new human sensing data like mobile phone positioning data to identify urban functional zones has still not been investigated. In this study, a new framework integrating remote sensing imagery and mobile phone positioning data was developed to analyze urban functional zones with landscape and human activity metrics. Landscapes metrics were calculated based on land cover from remote sensing images. Human activities were extracted from massive mobile phone positioning data. By integrating them, urban functional zones (urban center, sub-center, suburbs, urban buffer, transit region and ecological area were identified by a hierarchical clustering. Finally, gradient analysis in three typical transects was conducted to investigate the pattern of landscapes and human activities. Taking Shenzhen, China, as an example, the conducted experiment shows that the pattern of landscapes and human activities in the urban functional zones in Shenzhen does not totally conform to the classical urban theories. It demonstrates that the fusion of remote sensing imagery and human sensing data can characterize the complex urban spatial structure in Shenzhen well. Urban functional zones have the potential to act as bridges between the urban structure, human activity and urban planning policy, providing scientific support for rational urban planning and sustainable urban development policymaking.

  19. Protection of visual functions by human neural progenitors in a rat model of retinal disease.

    Directory of Open Access Journals (Sweden)

    David M Gamm

    2007-03-01

    Full Text Available A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat.Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90-100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed.Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in

  20. Amniotic fluid promotes the appearance of neural retinal progenitors and neurons in human RPE cell cultures.

    Science.gov (United States)

    Davari, Maliheh; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Sanie-Jahromi, Fateme; Ghaderi, Shima; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Akrami, Hassan; Haghighi, Massoud; Javidi-Azad, Fahimeh

    2013-01-01

    Retinal pigment epithelial (RPE) cells are capable of differentiating into retinal neurons when induced by the appropriate growth factors. Amniotic fluid contains a variety of growth factors that are crucial for the development of a fetus. In this study, the effects of human amniotic fluid (HAF) on primary RPE cell cultures were evaluated. RPE cells were isolated from the globes of postnatal human cadavers. The isolated cells were plated and grown in DMEM/F12 with 10% fetal bovine serum. To confirm the RPE identity of the cultured cells, they were immunocytochemically examined for the presence of the RPE cell-specific marker RPE65. RPE cultures obtained from passages 2-7 were treated with HAF and examined morphologically for 1 month. To determine whether retinal neurons or progenitors developed in the treated cultures, specific markers for bipolar (protein kinase C isomer α, PKCα), amacrine (cellular retinoic acid-binding protein I, CRABPI), and neural progenitor (NESTIN) cells were sought, and the amount of mRNA was quantified using real-time PCR. Treating RPE cells with HAF led to a significant decrease in the number of RPE65-positive cells, while PKCα- and CRABPI-positive cells were detected in the cultures. Compared with the fetal bovine serum-treated cultures, the levels of mRNAs quantitatively increased by 2-, 20- and 22-fold for NESTIN, PKCα, and CRABPI, respectively. The RPE cultures treated with HAF established spheres containing both pigmented and nonpigmented cells, which expressed neural progenitor markers such as NESTIN. This study showed that HAF can induce RPE cells to transdifferentiate into retinal neurons and progenitor cells, and that it provides a potential source for cell-based therapies to treat retinal diseases.

  1. Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and Vascular Permeability in Human Retinal Pigment Epithelial and Human Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and VEGF Activation

    Directory of Open Access Journals (Sweden)

    Hak Sung Lee

    2014-08-01

    Full Text Available Epigalloccatechin-3-gallate (EGCG is the main polyphenol component of green tea (leaves of Camellia sinensis. EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs and vascular endothelial growth factor (VEGF play a key role in the processes of extracellular matrix (ECM remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA and tumor necrosis factor alpha (TNF-α in human retinal pigment epithelial cells (HRPECs. EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2 by inhibiting generation of reactive oxygen species (ROS. EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs. Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31 on corneal neovascularization (CNV induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization.

  2. Significance of human retinal optic disk localization in various retinal eye diseases

    International Nuclear Information System (INIS)

    Basit, A.

    2011-01-01

    Optic Disk is one of the prominent features in human fundus images. Automatic localization and segmentation of optic disk can help in early diagnosis of diabetic retinopathies and preventing vision loss. In this paper robust method for optic disk detection and extraction of optic disk boundary is proposed based on morphological operations, smoothing filters and markers controlled watershed transform. This method has shown significant improvements in terms of detection and boundaries extraction of optic disk. This method used two types of markers: internal marker and external marker. These markers first modified the gradient magnitude image and then watershed transformation is applied on this modified gradient magnitude image for boundary extraction. The proposed method has optic disk detection success rate of 100% for Shifa and 87.6% for DIARETDB1 databases. Proposed method achieved average overlap of 51.19% for DIARETDB1 database and 73.98% for Shifa database which is higher than currents methods. Experimental results clearly demonstrate an efficient performance of the proposed algorithm. (author)

  3. Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

    Science.gov (United States)

    Kurokawa, Kazuhiro; Liu, Zhuolin; Crowell, James; Zhang, Furu; Miller, Donald T.

    2018-02-01

    The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellular level, we applied a customized correlation method to individual GCL somas, and found a mean time constant of activity of 0.57 s and spread of +/-0.1 s suggesting a range of physiological dynamics even in the same cell type. Extending our method to slower dynamics (from minutes to one year), time-lapse imaging and temporal speckle contrast revealed appendage and soma motion of resting microglial cells at the retinal surface.

  4. Admittance Control for Robot Assisted Retinal Vein Micro-Cannulation under Human-Robot Collaborative Mode

    Science.gov (United States)

    Gonenc, Berk; Iordachita, Iulian

    2017-01-01

    Retinal vein occlusion is one of the most common retinovascular diseases. Retinal vein cannulation is a potentially effective treatment method for this condition that currently lies, however, at the limits of human capabilities. In this work, the aim is to use robotic systems and advanced instrumentation to alleviate these challenges, and assist the procedure via a human-robot collaborative mode based on our earlier work on the Steady-Hand Eye Robot and force-sensing instruments. An admittance control method is employed to stabilize the cannula relative to the vein and maintain it inside the lumen during the injection process. A pre-stress strategy is used to prevent the tip of microneedle from getting out of vein in in prolonged infusions, and the performance is verified through simulations. PMID:29607442

  5. Admittance Control for Robot Assisted Retinal Vein Micro-Cannulation under Human-Robot Collaborative Mode.

    Science.gov (United States)

    Zhang, He; Gonenc, Berk; Iordachita, Iulian

    2017-10-01

    Retinal vein occlusion is one of the most common retinovascular diseases. Retinal vein cannulation is a potentially effective treatment method for this condition that currently lies, however, at the limits of human capabilities. In this work, the aim is to use robotic systems and advanced instrumentation to alleviate these challenges, and assist the procedure via a human-robot collaborative mode based on our earlier work on the Steady-Hand Eye Robot and force-sensing instruments. An admittance control method is employed to stabilize the cannula relative to the vein and maintain it inside the lumen during the injection process. A pre-stress strategy is used to prevent the tip of microneedle from getting out of vein in in prolonged infusions, and the performance is verified through simulations.

  6. Rapid, Directed Differentiation of Retinal Pigment Epithelial Cells from Human Embryonic or Induced Pluripotent Stem Cells

    OpenAIRE

    Foltz, LP; Clegg, DO

    2017-01-01

    We describe a robust method to direct the differentiation of pluripotent stem cells into retinal pigment epithelial cells (RPE). The purpose of providing a detailed and thorough protocol is to clearly demonstrate each step and to make this readily available to researchers in the field. This protocol results in a homogenous layer of RPE with minimal or no manual dissection needed. The method presented here has been shown to be effective for induced pluripotent stem cells (iPSC) and human embry...

  7. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre

    2007-06-01

    Full Text Available RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA.RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3 compared to controls

  8. Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    S N Leow

    Full Text Available To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs on retinal structure and function in Royal College of Surgeons (RCS rats.RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8 and placebo control group (n = 8. In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT. Retinal function was assessed by electroretinography (ERG 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies.No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells.Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.

  9. A new approach to optic disc detection in human retinal images using the firefly algorithm.

    Science.gov (United States)

    Rahebi, Javad; Hardalaç, Fırat

    2016-03-01

    There are various methods and algorithms to detect the optic discs in retinal images. In recent years, much attention has been given to the utilization of the intelligent algorithms. In this paper, we present a new automated method of optic disc detection in human retinal images using the firefly algorithm. The firefly intelligent algorithm is an emerging intelligent algorithm that was inspired by the social behavior of fireflies. The population in this algorithm includes the fireflies, each of which has a specific rate of lighting or fitness. In this method, the insects are compared two by two, and the less attractive insects can be observed to move toward the more attractive insects. Finally, one of the insects is selected as the most attractive, and this insect presents the optimum response to the problem in question. Here, we used the light intensity of the pixels of the retinal image pixels instead of firefly lightings. The movement of these insects due to local fluctuations produces different light intensity values in the images. Because the optic disc is the brightest area in the retinal images, all of the insects move toward brightest area and thus specify the location of the optic disc in the image. The results of implementation show that proposed algorithm could acquire an accuracy rate of 100 % in DRIVE dataset, 95 % in STARE dataset, and 94.38 % in DiaRetDB1 dataset. The results of implementation reveal high capability and accuracy of proposed algorithm in the detection of the optic disc from retinal images. Also, recorded required time for the detection of the optic disc in these images is 2.13 s for DRIVE dataset, 2.81 s for STARE dataset, and 3.52 s for DiaRetDB1 dataset accordingly. These time values are average value.

  10. Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.

    Science.gov (United States)

    Leow, S N; Luu, Chi D; Hairul Nizam, M H; Mok, P L; Ruhaslizan, R; Wong, H S; Wan Abdul Halim, Wan Haslina; Ng, M H; Ruszymah, B H I; Chowdhury, S R; Bastion, M L C; Then, K Y

    2015-01-01

    To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.

  11. Retinal Vascular and Oxygen Temporal Dynamic Responses to Light Flicker in Humans.

    Science.gov (United States)

    Felder, Anthony E; Wanek, Justin; Blair, Norman P; Shahidi, Mahnaz

    2017-11-01

    To mathematically model the temporal dynamic responses of retinal vessel diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF) to light flicker and to describe their responses to its cessation in humans. In 16 healthy subjects (age: 60 ± 12 years), retinal oximetry was performed before, during, and after light flicker stimulation. At each time point, five metrics were measured: retinal arterial and venous D (DA, DV) and SO2 (SO2A, SO2V), and OEF. Intra- and intersubject variability of metrics was assessed by coefficient of variation of measurements before flicker within and among subjects, respectively. Metrics during flicker were modeled by exponential functions to determine the flicker-induced steady state metric values and the time constants of changes. Metrics after the cessation of flicker were compared to those before flicker. Intra- and intersubject variability for all metrics were less than 6% and 16%, respectively. At the flicker-induced steady state, DA and DV increased by 5%, SO2V increased by 7%, and OEF decreased by 13%. The time constants of DA and DV (14, 15 seconds) were twofold smaller than those of SO2V and OEF (39, 34 seconds). Within 26 seconds after the cessation of flicker, all metrics were not significantly different from before flicker values (P ≥ 0.07). Mathematical modeling revealed considerable differences in the time courses of changes among metrics during flicker, indicating flicker duration should be considered separately for each metric. Future application of this method may be useful to elucidate alterations in temporal dynamic responses to light flicker due to retinal diseases.

  12. New medium used in the differentiation of human pluripotent stem cells to retinal cells is comparable to fetal human eye tissue.

    Science.gov (United States)

    Wang, Xiaobing; Xiong, Kai; Lin, Cong; Lv, Lei; Chen, Jing; Xu, Chongchong; Wang, Songtao; Gu, Dandan; Zheng, Hua; Yu, Hurong; Li, Yan; Xiao, Honglei; Zhou, Guomin

    2015-06-01

    Human pluripotent stem cells (hPSCs) have the potential to differentiate along the retinal lineage. However, most induction systems are dependent on multiple small molecular compounds such as Dkk-1, Lefty-A, and retinoic acid. In the present study, we efficiently differentiated hPSCs into retinal cells using a retinal differentiation medium (RDM) without the use of small molecular compounds. This novel differentiation system recapitulates retinal morphogenesis in humans, i.e. hPSCs gradually differentiate into optic vesicle-shaped spheres, followed by optic cup-shaped spheres and, lastly, retinal progenitor cells. Furthermore, at different stages, hPSC-derived retinal cells mirror the transcription factor expression profiles seen in their counterparts during human embryogenesis. Most importantly, hinge epithelium was found between the hPSC-derived neural retina (NR) and retinal pigment epithelium (RPE). These data suggest that our culture system provides a new method for generating hPSC-derived retinal cells that, for the first time, might be used in human transplantation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Increase of Universality in Human Brain during Mental Imagery from Visual Perception

    OpenAIRE

    Bhattacharya, Joydeep

    2009-01-01

    BACKGROUND: Different complex systems behave in a similar way near their critical points of phase transitions which leads to an emergence of a universal scaling behaviour. Universality indirectly implies a long-range correlation between constituent subsystems. As the distributed correlated processing is a hallmark of higher complex cognition, I investigated a measure of universality in human brain during perception and mental imagery of complex real-life visual object like visual art. METHODO...

  14. Human Blue Cone Opsin Regeneration Involves Secondary Retinal Binding with Analog Specificity.

    Science.gov (United States)

    Srinivasan, Sundaramoorthy; Fernández-Sampedro, Miguel A; Morillo, Margarita; Ramon, Eva; Jiménez-Rosés, Mireia; Cordomí, Arnau; Garriga, Pere

    2018-03-27

    Human color vision is mediated by the red, green, and blue cone visual pigments. Cone opsins are G-protein-coupled receptors consisting of an opsin apoprotein covalently linked to the 11-cis-retinal chromophore. All visual pigments share a common evolutionary origin, and red and green cone opsins exhibit a higher homology, whereas blue cone opsin shows more resemblance to the dim light receptor rhodopsin. Here we show that chromophore regeneration in photoactivated blue cone opsin exhibits intermediate transient conformations and a secondary retinoid binding event with slower binding kinetics. We also detected a fine-tuning of the conformational change in the photoactivated blue cone opsin binding site that alters the retinal isomer binding specificity. Furthermore, the molecular models of active and inactive blue cone opsins show specific molecular interactions in the retinal binding site that are not present in other opsins. These findings highlight the differential conformational versatility of human cone opsin pigments in the chromophore regeneration process, particularly compared to rhodopsin, and point to relevant functional, unexpected roles other than spectral tuning for the cone visual pigments. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. Alginate as a cell culture substrate for growth and differentiation of human retinal pigment epithelial cells.

    Science.gov (United States)

    Heidari, Razeih; Soheili, Zahra-Soheila; Samiei, Shahram; Ahmadieh, Hamid; Davari, Maliheh; Nazemroaya, Fatemeh; Bagheri, Abouzar; Deezagi, Abdolkhalegh

    2015-03-01

    The purpose of this study was to evaluate retinal pigment epithelium (RPE) cells' behavior in alginate beads that establish 3D environment for cellular growth and mimic extracellular matrix versus the conventional 2D monolayer culture. RPE cells were encapsulated in alginate beads by dripping alginate cell suspension into CaCl2 solution. Beads were suspended in three different media including Dulbecco's modified Eagle's medium (DMEM)/F12 alone, DMEM/F12 supplemented with 10 % fetal bovine serum (FBS), and DMEM/F12 supplemented with 30 % human amniotic fluid (HAF). RPE cells were cultivated on polystyrene under the same conditions as controls. Cell phenotype, cell proliferation, cell death, and MTT assay, immunocytochemistry, and real-time RT-PCR were performed to evaluate the effect of alginate on RPE cells characteristics and integrity. RPE cells can survive and proliferate in alginate matrixes. Immunocytochemistry analysis exhibited Nestin, RPE65, and cytokeratin expressions in a reasonable number of cultured cells in alginate beads. Real-time PCR data demonstrated high levels of Nestin, CHX10, RPE65, and tyrosinase gene expressions in RPE cells immobilized in alginate when compared to 2D monolayer culture systems. The results suggest that alginate can be used as a reliable scaffold for maintenance of RPE cells' integrity and in vitro propagation of human retinal progenitor cells for cell replacement therapies in retinal diseases.

  16. Induced Retro-Differentiation of Human Retinal Pigment Epithelial Cells on PolyHEMA.

    Science.gov (United States)

    Nazemroaya, Fatemeh; Soheili, Zahra-Soheila; Samiei, Shahram; Deezagi, Abdolkhalegh; Ahmadieh, Hamid; Davari, Malihe; Heidari, Razeih; Bagheri, Abouzar; Darvishalipour-Astaneh, Shamila

    2017-10-01

    Retinal pigment epithelium (RPE) cells represent a great potential to rescue degenerated cells of the damaged retina. Activation of the virtually plastic properties of RPE cells may aid in recovery of retinal degenerative disorders without the need for entire RPE sheet transplantation. Poly (2-hydroxyethyl methacrylate)(PolyHEMA) is one of the most important hydrogels in the biomaterials world. This hydrophobic polymer does not normally support attachment of mammalian cells. In the current study we investigated the effect of PolyHEMA as a cell culture substrate on the growth, differentiation, and plasticity of hRPE cells. hRPE cells were isolated from neonatal human globes and cultured on PolyHEMA and polystyrene substrates (as controls) in 24-well culture plates. DMEM/F12 was supplemented with 10% fetal bovine serum (FBS) and/or 30% human amniotic fluid (HAF) for cultured cells on polystyrene and PolyHEMA coated vessels. Morphology, rate of cell proliferation and cell death, MTT assay, immunocytochemistry and Real-Time RT-PCR were performed to investigate the effects of PolyHEMA on the growth and differentiation of cultured hRPE cells. Proliferation rate of the cells that had been cultured on PolyHEMA was reduced; PolyHEMA did not induce cell death in the hRPE cultures. hRPE cells cultured on PolyHEMA formed many giant spheroid colonies. The giant colonies were re-cultured and the presence of retinal progenitor markers and markers of hRPE cells were detected in cell cultures on PolyHEMA. PolyHEMA seems to be promising for both maintenance and de-differentiation of hRPE cells and expansion of the retinal progenitor cells from the cultures that are originated from hRPE cells. J. Cell. Biochem. 118: 3080-3089, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Kirstin B. Langer

    2018-04-01

    Full Text Available Summary: Retinal ganglion cells (RGCs are the projection neurons of the retina and transmit visual information to postsynaptic targets in the brain. While this function is shared among nearly all RGCs, this class of cell is remarkably diverse, comprised of multiple subtypes. Previous efforts have identified numerous RGC subtypes in animal models, but less attention has been paid to human RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated from human pluripotent stem cells (hPSCs and characterized defined subtypes through the expression of subtype-specific markers. Further investigation of these subtypes was achieved using single-cell transcriptomics, confirming the combinatorial expression of molecular markers associated with these subtypes, and also provided insight into more subtype-specific markers. Thus, the results of this study describe the derivation of RGC subtypes from hPSCs and will support the future exploration of phenotypic and functional diversity within human RGCs. : In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes. Keywords: iPSC, retina, retinal ganglion cell, RGC subtype, stem cell, ipRGC, alpha RGC, direction selective RGC, RNA-seq

  18. Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

    Science.gov (United States)

    Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

    2009-01-01

    Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

  19. Treatment Paradigms for Retinal and Macular Diseases Using 3-D Retina Cultures Derived From Human Reporter Pluripotent Stem Cell Lines.

    Science.gov (United States)

    Kaewkhaw, Rossukon; Swaroop, Manju; Homma, Kohei; Nakamura, Jutaro; Brooks, Matthew; Kaya, Koray Dogan; Chaitankar, Vijender; Michael, Sam; Tawa, Gregory; Zou, Jizhong; Rao, Mahendra; Zheng, Wei; Cogliati, Tiziana; Swaroop, Anand

    2016-04-01

    We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration.

  20. Effects of the Macular Carotenoid Lutein in Human Retinal Pigment Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Xiaoming Gong

    2017-12-01

    Full Text Available Retinal pigment epithelial (RPE cells are central to retinal health and homoeostasis. Oxidative stress-induced damage to the RPE occurs as part of the pathogenesis of age-related macular degeneration and neovascular retinopathies (e.g., retinopathy of prematurity, diabetic retinopathy. The xanthophyll carotenoids, lutein and zeaxanthin, are selectively taken up by the RPE, preferentially accumulated in the human macula, and transferred to photoreceptors. These macular xanthophylls protect the macula (and the broader retina via their antioxidant and photo-protective activities. This study was designed to investigate effects of various carotenoids (β-carotene, lycopene, and lutein on RPE cells subjected to either hypoxia or oxidative stress, in order to determine if there is effect specificity for macular pigment carotenoids. Using human RPE-derived ARPE-19 cells as an in vitro model, we exposed RPE cells to various concentrations of the specific carotenoids, followed by either graded hypoxia or oxidative stress using tert-butyl hydroperoxide (tBHP. The results indicate that lutein and lycopene, but not β-carotene, inhibit cell growth in undifferentiated ARPE-19 cells. Moreover, cell viability was decreased under hypoxic conditions. Pre-incubation of ARPE-19 cells with lutein or lycopene protected against tBHP-induced cell loss and cell co-exposure of lutein or lycopene with tBHP essentially neutralized tBHP-dependent cell death at tBHP concentrations up to 500 μM. Our findings indicate that lutein and lycopene inhibit the growth of human RPE cells and protect the RPE against oxidative stress-induced cell loss. These findings contribute to the understanding of the protective mechanisms attributable to retinal xanthophylls in eye health and retinopathies.

  1. Human V4 Activity Patterns Predict Behavioral Performance in Imagery of Object Color.

    Science.gov (United States)

    Bannert, Michael M; Bartels, Andreas

    2018-04-11

    Color is special among basic visual features in that it can form a defining part of objects that are engrained in our memory. Whereas most neuroimaging research on human color vision has focused on responses related to external stimulation, the present study investigated how sensory-driven color vision is linked to subjective color perception induced by object imagery. We recorded fMRI activity in male and female volunteers during viewing of abstract color stimuli that were red, green, or yellow in half of the runs. In the other half we asked them to produce mental images of colored, meaningful objects (such as tomato, grapes, banana) corresponding to the same three color categories. Although physically presented color could be decoded from all retinotopically mapped visual areas, only hV4 allowed predicting colors of imagined objects when classifiers were trained on responses to physical colors. Importantly, only neural signal in hV4 was predictive of behavioral performance in the color judgment task on a trial-by-trial basis. The commonality between neural representations of sensory-driven and imagined object color and the behavioral link to neural representations in hV4 identifies area hV4 as a perceptual hub linking externally triggered color vision with color in self-generated object imagery. SIGNIFICANCE STATEMENT Humans experience color not only when visually exploring the outside world, but also in the absence of visual input, for example when remembering, dreaming, and during imagery. It is not known where neural codes for sensory-driven and internally generated hue converge. In the current study we evoked matching subjective color percepts, one driven by physically presented color stimuli, the other by internally generated color imagery. This allowed us to identify area hV4 as the only site where neural codes of corresponding subjective color perception converged regardless of its origin. Color codes in hV4 also predicted behavioral performance in an

  2. Retinal oximetry in patients with ischaemic retinal diseases

    DEFF Research Database (Denmark)

    Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

    2017-01-01

    The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between...... retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic...... retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO2 ) were associated with present as well as increasing levels of DR. Four of six studies also found...

  3. Hydrostatic Pressure Does Not Cause Detectable Changes in Survival of Human Retinal Ganglion Cells

    Science.gov (United States)

    Osborne, Andrew; Aldarwesh, Amal; Rhodes, Jeremy D.; Broadway, David C.; Everitt, Claire; Sanderson, Julie

    2015-01-01

    Purpose Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina. PMID:25635827

  4. Phototoxicity and cytotoxicity of fullerol in human retinal pigment epithelial cells

    International Nuclear Information System (INIS)

    Wielgus, Albert R.; Zhao, Baozhong; Chignell, Colin F.; Hu, Dan-Ning; Roberts, Joan E.

    2010-01-01

    The water-soluble nanoparticle hydroxylated fullerene [fullerol, nano-C 60 (OH) 22-26 ] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have previously found that fullerol is both cytotoxic and phototoxic to human lens epithelial cells (HLE B-3) and that the endogenous antioxidant lutein blocked some of this phototoxicity. In the present study we have found that fullerol induces cytotoxic and phototoxic damage to human retinal pigment epithelial cells. Accumulation of nano-C 60 (OH) 22-26 in the cells was confirmed spectrophotometrically at 405 nm, and cell viability, cell metabolism and membrane permeability were estimated using trypan blue, MTS and LDH assays, respectively. Fullerol was cytotoxic toward hRPE cells maintained in the dark at concentrations higher than 10 μM. Exposure to an 8.5 J.cm -2 dose of visible light in the presence of > 5 μM fullerol induced TBARS formation and early apoptosis, indicating phototoxic damage in the form of lipid peroxidation. Pretreatment with 10 and 20 μM lutein offered some protection against fullerol photodamage. Using time resolved photophysical techniques, we have now confirmed that fullerol produces singlet oxygen with a quantum yield of Φ = 0.05 in D 2 O and with a range of 0.002-0.139 in various solvents. As our previous studies have shown that fullerol also produces superoxide in the presence of light, retinal phototoxic damage may occur through both type I (free radical) and type II (singlet oxygen) mechanisms. In conclusion, ocular exposure to fullerol, particularly in the presence of sunlight, may lead to retinal damage.

  5. Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function in a rat model of retinal degeneration.

    Science.gov (United States)

    Tzameret, Adi; Sher, Ifat; Belkin, Michael; Treves, Avraham J; Meir, Amilia; Nagler, Arnon; Levkovitch-Verbin, Hani; Rotenstreich, Ygal; Solomon, Arieh S

    2015-09-01

    Vision incapacitation and blindness associated with incurable retinal degeneration affect millions of people worldwide. In this study, 0.25×10(6) human bone marrow stem cells (hBM-MSCs) were transplanted epiretinally in the right eye of Royal College Surgeons (RCS) rats at the age of 28 days. Epiretinally transplanted cells were identified as a thin layer of cells along vitreous cavity, in close proximity to the retina or attached to the lens capsule, up to 6 weeks following transplantation. Epiretinal transplantation delayed photoreceptor degeneration and rescued retinal function up to 20 weeks following cell transplantation. Visual functions remained close to normal levels in epiretinal transplantation rats. No inflammation or any other adverse effects were observed in transplanted eyes. Our findings suggest that transplantation of hBM-MSCs as a thin epiretinal layer is effective for treatment of retinal degeneration in RCS rats, and that transplanting the cells in close proximity to the retina enhances hBM-MSC therapeutic effect compared with intravitreal injection. Copyright © 2015. Published by Elsevier B.V.

  6. An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration

    NARCIS (Netherlands)

    Lahdenranta, J.; Pasqualini, R.; Schlingemann, R. O.; Hagedorn, M.; Stallcup, W. B.; Bucana, C. D.; Sidman, R. L.; Arap, W.

    2001-01-01

    Abnormal angiogenesis accompanies many pathological conditions including cancer, inflammation, and eye diseases. Proliferative retinopathy because of retinal neovascularization is a leading cause of blindness in developed countries. Another major cause of irreversible vision loss is retinitis

  7. PlGF gene knockdown in human retinal pigment epithelial cells.

    Science.gov (United States)

    Akrami, Hassan; Soheili, Zahra-Soheila; Sadeghizadeh, Majid; Ahmadieh, Hamid; Rezaeikanavi, Mozhgan; Samiei, Shahram; Khalooghi, Keynoush

    2011-04-01

    To evaluate the knockdown of placental growth factor (PlGF) gene expression in human retinal pigment epithelium (RPE) cells and its effect on cell proliferation, apoptosis and angiogenic potential of RPE cells. Human RPE cells were isolated by dispase I solution and cultured in DMEM/F12 supplemented with 10% fetal calf serum (FCS). A small interfering RNA (siRNA) corresponding to PlGF mRNA and a scrambled siRNA (scRNA) were introduced into the cells. Cell proliferation and cell death were examined by ELISA. PlGF mRNA and protein were quantified by real-time polymerase chain reaction (PCR) and western blot. The levels of gene expression for human retinal pigment epithelium-specific protein 65 kDa (RPE65), cellular retinaldehyde-binding protein (CRALBP) and tyrosinase were examined by real-time PCR. The angiogenic activity of RPE cell-derived conditioned media was assayed by a tube formation assay using human umbilical vein endothelial cells (HUVECs). At a final siRNA concentration of 20 pmol/ml, the transfection efficiency was about 80%. The amount of PlGF transcripts was reduced to 10% after 36 h of incubation, and the amount of PlGF protein in culture supernatant was significantly decreased. Suppression of PlGF gene had no effect on RPE cell proliferation and survival, and there were no notable changes in the transcript levels of RPE65, CRALBP or tyrosinase for the cultures treated by siRNA cognate to PlGF. Vascular tube formation was efficiently reduced in HUVECs. Our findings present PlGF as a key modulator of angiogenic potential in RPE cells of the human retina.

  8. Analysis of the rdd locus in chicken: a model for human retinitis pigmentosa.

    Science.gov (United States)

    Burt, David W; Morrice, David R; Lester, Douglas H; Robertson, Graeme W; Mohamed, Moin D; Simmons, Ian; Downey, Louise M; Thaung, Caroline; Bridges, Leslie R; Paton, Ian R; Gentle, Mike; Smith, Jacqueline; Hocking, Paul M; Inglehearn, Chris F

    2003-04-30

    To identify the locus responsible for the blind mutation rdd (retinal dysplasia and degeneration) in chickens and to further characterise the rdd phenotype. The eyes of blind and sighted birds were subjected to ophthalmic, morphometric and histopathological examination to confirm and extend published observations. Electroretinography was used to determine age of onset. Birds were crossed to create pedigrees suitable for genetic mapping. DNA samples were obtained and subjected to a linkage search. Measurement of IOP, axial length, corneal diameter, and eye weight revealed no gross morphological changes in the rdd eye. However, on ophthalmic examination, rdd homozygotes have a sluggish pupillary response, atrophic pecten, and widespread pigmentary disturbance that becomes more pronounced with age. Older birds also have posterior subcapsular cataracts. At three weeks of age, homozygotes have a flat ERG indicating severe loss of visual function. Pathological examination shows thinning of the RPE, ONL, photoreceptors and INL, and attenuation of the ganglion cell layer. From 77 classified backcross progeny, 39 birds were blind and 38 sighted. The rdd mutation was shown to be sex-linked and not autosomal as previously described. Linkage analysis mapped the rdd locus to a small region of the chicken Z chromosome with homologies to human chromosomes 5q and 9p. Ophthalmic, histopathologic, and electrophysiological observations suggest rdd is similar to human recessive retinitis pigmentosa. Linkage mapping places rdd in a region homologous to human chromosomes 9p and 5q. Candidate disease genes or loci include PDE6A, WGN1, and USH2C. This is the first use of genetic mapping in a chicken model of human disease.

  9. Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

    Science.gov (United States)

    Harwerth, Ronald S.; Quigley, Harry A.

    2007-01-01

    Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

  10. Application of satellite imagery to monitoring human rights abuse of vulnerable communities, with minimal risk to relief staff

    Energy Technology Data Exchange (ETDEWEB)

    Lavers, C; Bishop, C; Hawkins, O; Grealey, E; Cox, C; Thomas, D; Trimel, S, E-mail: brnc-radarcomms1@nrta.mod.u [Sensors Team, Plymouth University at Britannia Royal Naval College, Dartmouth (United Kingdom); DMC International Imaging, Tycho House, Surrey Research Park, Guildford (United Kingdom); Qinetiq, Cody Technology Park, Cody Building, Ively Road, Farnborough (United Kingdom); Humanitarian Aid Relief Trust (HART), 3 Arnellan House, Kingsbury, London (United Kingdom); Amnesty International USA, 5 Penn Plaza, New York (United States)

    2009-07-01

    Space imagery offers remote surveillance of ethnic people groups at risk of human rights abuse. We highlight work in alleged violations in Burma and Sudan, using satellite imagery for verification with Amnesty International. We consider how imaging may effectively support small to medium-sized Non Governmental Organisations and charities, e.g. HART, working in dangerous zones on the ground. Satellite based sensing applications are now at a sufficiently mature stage for moderate Governmental funding levels to help prevent human rights abuse, rather than the greater cost of rebuilding communities and healing sectarian divisions after abuse has taken place.

  11. Application of satellite imagery to monitoring human rights abuse of vulnerable communities, with minimal risk to relief staff

    International Nuclear Information System (INIS)

    Lavers, C; Bishop, C; Hawkins, O; Grealey, E; Cox, C; Thomas, D; Trimel, S

    2009-01-01

    Space imagery offers remote surveillance of ethnic people groups at risk of human rights abuse. We highlight work in alleged violations in Burma and Sudan, using satellite imagery for verification with Amnesty International. We consider how imaging may effectively support small to medium-sized Non Governmental Organisations and charities, e.g. HART, working in dangerous zones on the ground. Satellite based sensing applications are now at a sufficiently mature stage for moderate Governmental funding levels to help prevent human rights abuse, rather than the greater cost of rebuilding communities and healing sectarian divisions after abuse has taken place.

  12. Efflux protein expression in human stem cell-derived retinal pigment epithelial cells.

    Directory of Open Access Journals (Sweden)

    Kati Juuti-Uusitalo

    Full Text Available Retinal pigment epithelial (RPE cells in the back of the eye nourish photoreceptor cells and form a selective barrier that influences drug transport from the blood to the photoreceptor cells. At the molecular level, ATP-dependent efflux transporters have a major role in drug delivery in human RPE. In this study, we assessed the relative expression of several ATP-dependent efflux transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP, the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human embryonic stem cells (hESC and RPE derived from the hESC (hESC-RPE. Our findings revealed that the gene expression of ATP-dependent efflux transporters MRP1, -3, -4, -5, and p-gp fluctuated during hESC-RPE maturation from undifferentiated hESC to fusiform, epithelioid, and finally to cobblestone hESC-RPE. Epithelioid hESC-RPE had the highest expression of MRP1, -3, -4, and P-gp, whereas the most mature cobblestone hESC-RPE had the highest expression of MRP5 and MRP6. These findings indicate that a similar efflux protein profile is shared between hESC-RPE and the human RPE cell line, ARPE-19, and suggest that hESC-RPE cells are suitable in vitro RPE models for drug transport studies. Embryonic stem cell model might provide a novel tool to study retinal cell differentiation, mechanisms of RPE-derived diseases, drug testing and targeted drug therapy.

  13. Differential behavioral outcomes following neonatal versus fetal human retinal pigment epithelial cell striatal implants in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz

    2017-01-01

    Following the failure of a Phase II clinical study evaluating human retinal pigment epithelial (hRPE) cell implants as a potential treatment option for Parkinson's disease, speculation has centered on implant function and survival as possible contributors to the therapeutic outcomes. We recently ...

  14. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  15. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  16. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  17. In-vivo imaging of blood flow in human retinal vessels using color Doppler optical coherence tomography

    Science.gov (United States)

    Yazdanfar, Siavash; Rollins, Andrew M.; Izatt, Joseph A.

    1999-04-01

    Quantification of retinal blood flow may lead to a better understanding of the progression and treatment of several ocular disorders, including diabetic retinopathy, age- related macular degeneration, and glaucoma. Current techniques, such as fluorescein angiography and laser Doppler velocimetry are limited, failing to provide sufficient information to the clinician. Color Doppler optical coherence tomography (CDOCT) is a novel technique using coherent heterodyne detection for simultaneous cross- sectional imaging of tissue microstructure and blood flow. This technique is capable of high spatial and velocity resolution imaging in highly scattering media. We implemented CDOCT for retinal blood flow mapping in human subjects. No dilation of the pupil was necessary. CDOCT is demonstrated for determining bidirectional flow in sub- 100micrometers diameter vessels in the retina. Additionally, we calculated Doppler broadening using the variance of depth- resolved spectra to identify regions with large velocity gradients within the Xenopus heart. This technique may be useful in quantifying local tissue perfusion in highly vascular retinal tissue.

  18. Two-photon excited autofluorescence imaging of human retinal pigment epithelial cells

    Science.gov (United States)

    Han, Meng; Blindewald-Wittich, Almut; Holz, Frank G.; Giese, Günter; Niemz, Markolf H.; Snyder, Sarah; Sun, Hui; Yu, Jiayi; Agopov, Michael; La Schiazza, Olivier; Bille, Josef F.

    2006-01-01

    Degeneration of retinal pigment epithelial (RPE) cells severely impairs the visual function of retina photoreceptors. However, little is known about the events that trigger the death of RPE cells at the subcellular level. Two-photon excited autofluorescence (TPEF) imaging of RPE cells proves to be well suited to investigate both the morphological and the spectral characteristics of the human RPE cells. The dominant fluorophores of autofluorescence derive from lipofuscin (LF) granules that accumulate in the cytoplasm of the RPE cells with increasing age. Spectral TPEF imaging reveals the existence of abnormal LF granules with blue shifted autofluorescence in RPE cells of aging patients and brings new insights into the complicated composition of the LF granules. Based on a proposed two-photon laser scanning ophthalmoscope, TPEF imaging of the living retina may be valuable for diagnostic and pathological studies of age related eye diseases.

  19. Lack of FasL expression in cultured human retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Kaestel, C G; Madsen, H O; Prause, J U

    2001-01-01

    Retinal pigment epithelial (RPE) cells have been proposed to play a part in maintaining the eye as an immune privileged organ. However, our knowledge of the implicated mechanism is still sparse. Fas ligand (FasL) expression of RPE cells is generally recognized to be essential for the immune...... privilege of the eye, but due to contradictory published results, it is unclear whether RPE cells express this molecule. The purpose of this study was to investigate the expression of FasL in RPE cells in vitro and in vivo. Cultured human fetal and adult RPE cells were examined by flow cytometry, Western...... blotting, RT-PCR and RNase Protection assay for FasL expression. Additionally, sections of ocular tissue were stained for FasL by immunohistochemistry. None of the used methods indicated FasL expression in cultured fetal or adult RPE cells of various passages. However, RPE cells in vivo, as judged from...

  20. Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

    Science.gov (United States)

    Hammoum, Imane; Benlarbi, Maha; Dellaa, Ahmed; Szabó, Klaudia; Dékány, Bulcsú; Csaba, Dávid; Almási, Zsuzsanna; Hajdú, Rozina I; Azaiz, Rached; Charfeddine, Ridha; Lukáts, Ákos; Ben Chaouacha-Chekir, Rafika

    2017-09-01

    The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases. © 2017 Wiley Periodicals, Inc.

  1. The effects of platelet gel on cultured human retinal pigment epithelial (hRPE cells

    Directory of Open Access Journals (Sweden)

    Sahar Balagholi

    2017-11-01

    Full Text Available The positive role of platelet gel (PG in tissue regeneration is well known, however, other characteristics of PG still remain to be determined. We investigated cellular and molecular changes in cultured human retinal pigment epithelial (hRPE cells when treated with different concentrations of PG named PG1, PG2, and PG3. hRPE cells were isolated from donor eyes of two newborn children, within 24 hours after their death. The cells were treated with three concentrations of PG for 7 days: 3 × 104/ml (PG1, 6 × 104/ml (PG2, and 9 × 104/ml (PG3. Fetal bovine serum was used as a control. Immunocytochemistry was performed with anti-RPE65 (H-85, anti-Cytokeratin 8/18 (NCL-5D3, and anti-PAX6 antibody. We used MTT assay to determine cell viability. Gene expressions of PAX6, MMP2, RPE65, ACTA2, MKI67, MMP9, and KDR were analyzed using real-time PCR. A significant increase in viability was observed for PG3-treated cells compared to control (p = 0.044 and compared to PG1 group (p = 0.027, on day 7. Cellular elongation together with dendritiform extensions were observed in PG-treated cells on days 1 and 3, while epithelioid morphology was observed on day 7. All cells were immunoreactive for RPE65, cytokeratin 8/18, and PAX6. No significant change was observed in the expression of MKI67 and PAX6, but the expressions of MMP2, MMP9, ACTA2, and KDR were significantly higher in PG2-treated cells compared to controls (p < 0.05. Our results indicate that increased concentration of PG and extended exposure time have positive effects on viability of hRPE cells. PG may be useful for hRPE cell encapsulation in retinal cell replacement therapy.

  2. Biological effects of cigarette smoke in cultured human retinal pigment epithelial cells.

    Directory of Open Access Journals (Sweden)

    Alice L Yu

    Full Text Available The goal of the present study was to determine whether treatment with cigarette smoke extract (CSE induces cell loss, cellular senescence, and extracellular matrix (ECM synthesis in primary human retinal pigment epithelial (RPE cells. Primary cultured human RPE cells were exposed to 2, 4, 8, and 12% of CSE concentration for 24 hours. Cell loss was detected by cell viability assay. Lipid peroxidation was assessed by loss of cis-parinaric acid (PNA fluorescence. Senescence-associated ß-galactosidase (SA-ß-Gal activity was detected by histochemical staining. Expression of apolipoprotein J (Apo J, connective tissue growth factor (CTGF, fibronectin, and laminin were examined by real-time PCR, western blot, or ELISA experiments. The results showed that exposure of cells to 12% of CSE concentration induced cell death, while treatment of cells with 2, 4, and 8% CSE increased lipid peroxidation. Exposure to 8% of CSE markedly increased the number of SA-ß-Gal positive cells to up to 82%, and the mRNA expression of Apo J, CTGF, and fibronectin by approximately 3-4 fold. Treatment with 8% of CSE also increased the protein expression of Apo J and CTGF and the secretion of fibronectin and laminin. Thus, treatment with CSE can induce cell loss, senescent changes, and ECM synthesis in primary human RPE cells. It may be speculated that cigarette smoke could be involved in cellular events in RPE cells as seen in age-related macular degeneration.

  3. Transport of protons and lactate in cultured human fetal retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Cour, Morten la; Ming Lui, Ge

    2000-01-01

    Electron microscopy, intracellular pH, monocarboxylate transport, pigment epithelium of eye, proton-lactate cotransport, retinal metabolism, sodium/proton exchange......Electron microscopy, intracellular pH, monocarboxylate transport, pigment epithelium of eye, proton-lactate cotransport, retinal metabolism, sodium/proton exchange...

  4. Hydrostatic pressure does not cause detectable changes in survival of human retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Andrew Osborne

    Full Text Available Elevated intraocular pressure (IOP is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP. The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC survival in the human retina was investigated.A chamber was designed to expose cells to increased HP (constant and fluctuating. Accurate pressure control (10-100 mmHg was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs from donor eyes (<24 h post mortem were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD. Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1 and RGC number by immunohistochemistry (NeuN. Activated p38 and JNK were detected by Western blot.Exposure of HORCs to constant (60 mmHg or fluctuating (10-100 mmHg; 1 cycle/min pressure for 24 or 48 h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1 or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24 h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100 mmHg; 1 cycle/min for 15, 30, 60 and 90 min durations, whereas OGD (3 h increased activation of p38 and JNK, remaining elevated for 90 min post-OGD.Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina.

  5. Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity.

    Science.gov (United States)

    Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen; Fahrenkrug, Jan; Kiilgaard, Jens Folke

    2017-06-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1 (GDM1)." Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin-ir (0.63-0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin-ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin-ir RGCs, which most likely are involved in different functions. © 2017 Wiley Periodicals, Inc.

  6. Optimized formation of detergent micelles of beta-carotene and retinal production using recombinant human beta,beta-carotene 15,15'-monooxygenase.

    Science.gov (United States)

    Kim, Nam-Hee; Kim, Yeong-Su; Kim, Hye-Jung; Oh, Deok-Kun

    2008-01-01

    The formation of beta-carotene detergent micelles and their conversion into retinal by recombinant human beta,beta-carotene 15,15'-monooxygenase was optimized under aqueous conditions. Toluene was the most hydrophobic among the organic solvents tested; thus, it was used to dissolve beta-carotene, which is a hydrophobic compound. Tween 80 was selected as the detergent because it supported the highest level of retinal production among all of the detergents tested. The maximum production of retinal was achieved in detergent micelles containing 200 mg/L of beta-carotene and 2.4% (w/v) Tween 80. Under these conditions, the recombinant enzyme produced 97 mg/L of retinal after 16 h with a conversion yield of 48.5% (w/w). The amount of retinal produced, which is the highest ever reported, is a result of the ability of our system to dissolve large amounts of beta-carotene.

  7. Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

    DEFF Research Database (Denmark)

    Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

    2018-01-01

    PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

  8. Expression and regulation of enzymes in the ceramide metabolic pathway in human retinal pigment epithelial cells and their relevance to retinal degeneration.

    Science.gov (United States)

    Zhu, DanHong; Sreekumar, Parameswaran G; Hinton, David R; Kannan, Ram

    2010-03-31

    Ceramide and its metabolic derivatives are important modulators of cellular apoptosis and proliferation. Dysregulation or imbalance of their metabolic pathways may promote the development of retinal degeneration. The aim of this study was to identify the expression and regulation of key enzymes of the ceramide pathway in retinal pigment epithelial (RPE) cells. RT-PCR was used to screen the enzymes involved in ceramide metabolism that are expressed in RPE. Over-expression of neutral sphingomyelinase-2 (SMPD3) or sphingosine kinase 1 (Sphk1) in ARPE-19 cells was achieved by transient transfection of SMPD3 or Sphk1 cDNA subcloned into an expression vector. The number of apoptotic or proliferating cells was determined using TUNEL and BrdU assays, respectively. Neutral sphingomyelinase-1, neutral sphingomyelinase-2, acidic ceramidase, ceramide kinase, SphK1 and Sphk2 were expressed in both ARPE-19 and early passage human fetal RPE (fRPE) cells, while alkaline ceramidase 2 was only expressed in fRPE cells. Over-expression of SMPD3 decreased RPE cell proliferation and increased cell apoptosis. The percentage of apoptotic cells increased proportionally with the amount of transfected SMPD3 DNA. Over-expression of SphK1 promoted cell proliferation and protected ARPE-19 cells from ceramide-induced apoptosis. The effect of C(2) ceramide on induction of apoptosis was evaluated in polarized vs. non-polarized RPE cultures; polarization of RPE was associated with much reduced apoptosis in response to ceramide. In conclusion, RPE cells possess the synthetic machinery for the production of ceramide, sphingosine, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P). Over-expression of SMPD3 may increase cellular ceramide levels, leading to enhanced cell death and arrested cell proliferation. The selective induction of apoptosis in non-polarized RPE cultures by C(2) ceramide suggests that increased ceramide levels will preferentially affect non-polarized RPE, as are found in

  9. Imagery of a moving object: the role of occipital cortex and human MT/V5+.

    Science.gov (United States)

    Kaas, Amanda; Weigelt, Sarah; Roebroeck, Alard; Kohler, Axel; Muckli, Lars

    2010-01-01

    Visual imagery--similar to visual perception--activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short-term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral-occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1-3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences.

  10. Cytotoxicity and genotoxicity of bacterial magnetosomes against human retinal pigment epithelium cells

    Science.gov (United States)

    Qi, Lei; Lv, Xiujuan; Zhang, Tongwei; Jia, Peina; Yan, Ruiying; Li, Shuli; Zou, Ruitao; Xue, Yuhua; Dai, Liming

    2016-06-01

    A variety of nanomaterials have been developed for ocular diseases. The ability of these nanomaterials to pass through the blood-ocular barrier and their biocompatibility are essential characteristics that must be considered. Bacterial magnetosomes (BMs) are a type of biogenic magnetic nanomaterials synthesized by magnetotactic bacteria. Due to their unique biomolecular membrane shell and narrow size distribution of approximately 30 nm, BMs can pass through the blood-brain barrier. The similarity of the blood-ocular barrier to the blood-brain barrier suggests that BMs have great potential as treatments for ocular diseases. In this work, BMs were isolated from magnetotactic bacteria and evaluated in various cytotoxicity and genotoxicity studies in human retinal pigment epithelium (ARPE-19) cells. The BMs entered ARPE-19 cells by endocytosis after a 6-h incubation and displayed much lower cytotoxicity than chemically synthesized magnetic nanoparticles (MNPs). MNPs exhibited significantly higher genotoxicity than BMs and promoted the expression of Bax (the programmed cell death acceleration protein) and the induction of greater cell necrosis. In BM-treated cells, apoptosis tended to be suppressed via increased expression of the Bcl-2 protein. In conclusion, BMs display excellent biocompatibility and potential for use in the treatment of ocular diseases.

  11. Optical coherence tomography noise modeling and fundamental bounds on human retinal layer segmentation accuracy (Conference Presentation)

    Science.gov (United States)

    DuBose, Theodore B.; Milanfar, Peyman; Izatt, Joseph A.; Farsiu, Sina

    2016-03-01

    The human retina is composed of several layers, visible by in vivo optical coherence tomography (OCT) imaging. To enhance diagnostics of retinal diseases, several algorithms have been developed to automatically segment one or more of the boundaries of these layers. OCT images are corrupted by noise, which is frequently the result of the detector noise and speckle, a type of coherent noise resulting from the presence of several scatterers in each voxel. However, it is unknown what the empirical distribution of noise in each layer of the retina is, and how the magnitude and distribution of the noise affects the lower bounds of segmentation accuracy. Five healthy volunteers were imaged using a spectral domain OCT probe from Bioptigen, Inc, centered at 850nm with 4.6µm full width at half maximum axial resolution. Each volume was segmented by expert manual graders into nine layers. The histograms of intensities in each layer were then fit to seven possible noise distributions from the literature on speckle and image processing. Using these empirical noise distributions and empirical estimates of the intensity of each layer, the Cramer-Rao lower bound (CRLB), a measure of the variance of an estimator, was calculated for each boundary layer. Additionally, the optimum bias of a segmentation algorithm was calculated, and a corresponding biased CRLB was calculated, which represents the improved performance an algorithm can achieve by using prior knowledge, such as the smoothness and continuity of layer boundaries. Our general mathematical model can be easily adapted for virtually any OCT modality.

  12. Human cadaver retina model for retinal heating during corneal surgery with a femtosecond laser

    Science.gov (United States)

    Sun, Hui; Fan, Zhongwei; Yun, Jin; Zhao, Tianzhuo; Yan, Ying; Kurtz, Ron M.; Juhasz, Tibor

    2014-02-01

    Femtosecond lasers are widely used in everyday clinical procedures to perform minimally invasive corneal refractive surgery. The intralase femtosecond laser (AMO Corp. Santa Ana, CA) is a common example of such a laser. In the present study a numerical simulation was developed to quantify the temperature rise in the retina during femtosecond intracorneal surgery. Also, ex-vivo retinal heating due to laser irradiation was measured with an infrared thermal camera (Fluke Corp. Everett, WA) as a validation of the simulation. A computer simulation was developed using Comsol Multiphysics to calculate the temperature rise in the cadaver retina during femtosecond laser corneal surgery. The simulation showed a temperature rise of less than 0.3 degrees for realistic pulse energies for the various repetition rates. Human cadaver retinas were irradiated with a 150 kHz Intralase femtosecond laser and the temperature rise was measured withan infrared thermal camera. Thermal camera measurements are in agreement with the simulation. During routine femtosecond laser corneal surgery with normal clinical parameters, the temperature rise is well beneath the threshold for retina damage. The simulation predictions are in agreement with thermal measurements providing a level of experimental validation.

  13. Mechanisms of selective delivery of xanthophylls to retinal pigment epithelial cells by human lipoproteins.

    Science.gov (United States)

    Thomas, Sara E; Harrison, Earl H

    2016-10-01

    The xanthophylls, lutein and zeaxanthin, are dietary carotenoids that selectively accumulate in the macula of the eye providing protection against age-related macular degeneration. To reach the macula, carotenoids cross the retinal pigment epithelium (RPE). Xanthophylls and β-carotene mostly associate with HDL and LDL, respectively. HDL binds to cells via a scavenger receptor class B1 (SR-B1)-dependent mechanism, while LDL binds via the LDL receptor. Using an in-vitro, human RPE cell model (ARPE-19), we studied the mechanisms of carotenoid uptake into the RPE by evaluating kinetics of cell uptake when delivered in serum or isolated LDL or HDL. For lutein and β-carotene, LDL delivery resulted in the highest rates and extents of uptake. In contrast, HDL was more effective in delivering zeaxanthin and meso-zeaxanthin leading to the highest rates and extents of uptake of all four carotenoids. Inhibitors of SR-B1 suppressed zeaxanthin delivery via HDL. Results show a selective HDL-mediated uptake of zeaxanthin and meso-zeaxanthin via SR-B1 and a LDL-mediated uptake of lutein. This demonstrates a plausible mechanism for the selective accumulation of zeaxanthin greater than lutein and xanthophylls over β-carotene in the retina. We found no evidence of xanthophyll metabolism to apocarotenoids or lutein conversion to meso-zeaxanthin. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. Landsat Imagery-Based Above Ground Biomass Estimation and Change Investigation Related to Human Activities

    Directory of Open Access Journals (Sweden)

    Chaofan Wu

    2016-02-01

    Full Text Available Forest biomass is a significant indicator for substance accumulation and forest succession, and a spatiotemporal biomass map would provide valuable information for forest management and scientific planning. In this study, Landsat imagery and field data cooperated with a random forest regression approach were used to estimate spatiotemporal Above Ground Biomass (AGB in Fuyang County, Zhejiang Province of East China. As a result, the AGB retrieval showed an increasing trend for the past decade, from 74.24 ton/ha in 2004 to 99.63 ton/ha in 2013. Topography and forest management were investigated to find their relationships with the spatial distribution change of biomass. In general, the simulated AGB increases with higher elevation, especially in the range of 80–200 m, wherein AGB acquires the highest increase rate. Moreover, the forest policy of ecological forest has a positive effect on the AGB increase, particularly within the national level ecological forest. The result in this study demonstrates that human activities have a great impact on biomass distribution and change tendency. Furthermore, Landsat image-based biomass estimates would provide illuminating information for forest policy-making and sustainable development.

  15. Multi-level communication of human retinal pigment epithelial cells via tunneling nanotubes.

    Directory of Open Access Journals (Sweden)

    Dierk Wittig

    Full Text Available BACKGROUND: Tunneling nanotubes (TNTs may offer a very specific and effective way of intercellular communication. Here we investigated TNTs in the human retinal pigment epithelial (RPE cell line ARPE-19. Morphology of TNTs was examined by immunostaining and scanning electron microscopy. To determine the function of TNTs between cells, we studied the TNT-dependent intercellular communication at different levels including electrical and calcium signalling, small molecular diffusion as well as mitochondrial re-localization. Further, intercellular organelles transfer was assayed by FACS analysis. METHODOLOGY AND PRINCIPAL FINDINGS: Microscopy showed that cultured ARPE-19 cells are frequently connected by TNTs, which are not attached to the substratum. The TNTs were straight connections between cells, had a typical diameter of 50 to 300 nm and a length of up to 120 µm. We observed de novo formation of TNTs by diverging from migrating cells after a short time of interaction. Scanning electron microscopy confirmed characteristic features of TNTs. Fluorescence microscopy revealed that TNTs between ARPE-19 cells contain F-actin but no microtubules. Depolymerisation of F-actin, induced by addition of latrunculin-B, led to disappearance of TNTs. Importantly, these TNTs could function as channels for the diffusion of small molecules such as Lucifer Yellow, but not for large molecules like Dextran Red. Further, organelle exchange between cells via TNTs was observed by microscopy. Using Ca²⁺ imaging we show the intercellular transmission of calcium signals through TNTs. Mechanical stimulation led to membrane depolarisation, which expand through TNT connections between ARPE-19 cells. We further demonstrate that TNTs can mediate electrical coupling between distant cells. Immunolabelling for Cx43 showed that this gap junction protein is interposed at one end of 44% of TNTs between ARPE-19 cells. CONCLUSIONS AND SIGNIFICANCE: Our observations indicate that

  16. Behavior of a Spontaneously Arising Human Retinal Pigment Epithelial Cell Line Cultivated on Thin Alginate Film.

    Science.gov (United States)

    Najafabadi, Hoda Shams; Soheili, Zahra-Soheila; Ganji, Shahla Mohammad

    2015-01-01

    A cell line spontaneously derived from human retinal pigment epithelium (hRPE) was cultured on alginate film gelatinized with different concentrations of neurobasal cell culture medium (NCCM) to assess its growth and morphological behavior on this naturally occurring polysaccharide. Neonatal human globes were used to isolate hRPE cells. They were cultured in Dulbecco's modified Eagle's-medium-and-Ham's-F12-medium-(DMEM/F12) supplemented with 10% fetal bovine serum (FBS). Cultures were continuously studied using phase contrast microscopy. After the nineth passage, cells were characterized through immunocytochemical analysis for Oct4, Chx10, and Pax6 and Ki67 markers. In each well of a 6-well microplate, 1 and 2% weight/volume (w/v) alginate in deionized water was added and gelatinized using 1× and 10× NCCM. hRPE cells were cultured at a density of 2 × 105 cells/well in alginate-coated microplates. After 5 days, hRPE colonies were harvested and re-plated on polystyrene substrates. Morphology and growth of hRPE cultures were determined during the next 2 weeks. The first few passages of the cultures were purely hRPE cells that revealed typical morphological features of the pigmented epithelium. They made spaces, devoid of cells, between hRPE cell monolayer and fill in the unoccupied spaces. They grew faster than native RPE cells and rapidly overgrew. Immunocytochemical test revealed that the founded cells expressed Chx10, Pax6, Ki67 and Oct4. The hRPE cells survived unlimitedly on alginate film and formed giant adjoining colonies. After re-plating, hRPE colonies adhered quickly on polystyrene and displayed native hRPE morphological features. Alginate film can support the survival and growth of hRPE cells and induce the cells to re-organize in tissue-like structures.

  17. Three-dimensional neuroepithelial culture from human embryonic stem cells and its use for quantitative conversion to retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Yu Zhu

    Full Text Available A goal in human embryonic stem cell (hESC research is the faithful differentiation to given cell types such as neural lineages. During embryonic development, a basement membrane surrounds the neural plate that forms a tight, apico-basolaterally polarized epithelium before closing to form a neural tube with a single lumen. Here we show that the three-dimensional epithelial cyst culture of hESCs in Matrigel combined with neural induction results in a quantitative conversion into neuroepithelial cysts containing a single lumen. Cells attain a defined neuroepithelial identity by 5 days. The neuroepithelial cysts naturally generate retinal epithelium, in part due to IGF-1/insulin signaling. We demonstrate the utility of this epithelial culture approach by achieving a quantitative production of retinal pigment epithelial (RPE cells from hESCs within 30 days. Direct transplantation of this RPE into a rat model of retinal degeneration without any selection or expansion of the cells results in the formation of a donor-derived RPE monolayer that rescues photoreceptor cells. The cyst method for neuroepithelial differentiation of pluripotent stem cells is not only of importance for RPE generation but will also be relevant to the production of other neuronal cell types and for reconstituting complex patterning events from three-dimensional neuroepithelia.

  18. Noninvasive near infrared autofluorescence imaging of retinal pigment epithelial cells in the human retina using adaptive optics.

    Science.gov (United States)

    Liu, Tao; Jung, HaeWon; Liu, Jianfei; Droettboom, Michael; Tam, Johnny

    2017-10-01

    The retinal pigment epithelial (RPE) cells contain intrinsic fluorophores that can be visualized using infrared autofluorescence (IRAF). Although IRAF is routinely utilized in the clinic for visualizing retinal health and disease, currently, it is not possible to discern cellular details using IRAF due to limits in resolution. We demonstrate that the combination of adaptive optics (AO) with IRAF (AO-IRAF) enables higher-resolution imaging of the IRAF signal, revealing the RPE mosaic in the living human eye. Quantitative analysis of visualized RPE cells in 10 healthy subjects across various eccentricities demonstrates the possibility for in vivo density measurements of RPE cells, which range from 6505 to 5388 cells/mm 2 for the areas measured (peaking at the fovea). We also identified cone photoreceptors in relation to underlying RPE cells, and found that RPE cells support on average up to 18.74 cone photoreceptors in the fovea down to an average of 1.03 cone photoreceptors per RPE cell at an eccentricity of 6 mm. Clinical application of AO-IRAF to a patient with retinitis pigmentosa illustrates the potential for AO-IRAF imaging to become a valuable complementary approach to the current landscape of high resolution imaging modalities.

  19. Human-induced geomorphology: Modeling slope failure in Dominical, Costa Rica using Landsat imagery

    Science.gov (United States)

    Miller, Andrew J.

    Unchecked human development has ravaged the region between Dominical and Uvita, Costa Rica. Much of the development transition has been driven by tourism and further foreign direct investment in residential, service and commercial enterprises. The resulting land-use/land-cover change has removed traditional forest cover in exchange for impervious surfaces, physical structures, and bare ground which is no longer mechanically supported by woody vegetation. Combined with a tropical climate, deeply weathered soils and lithography which are prone to erosion, land cover change has led to an increase in slope failure occurrences. Given the remoteness of the Dominical-Uvita region, its rate of growth and the lack of monitoring, new techniques for monitoring land use and slope failure susceptibility are needed. Two new indices are presented here that employ a Digital Elevation Model (DEM) and widely available Landsat imagery to assist in this endeavor. The first index, or Vegetation Influenced Landslide Index (VILI), incorporates slope derived from a DEM and Lu et al.'s (2007) Surface Cover Index to quantify vegetative cover as a means of mechanical stabilization in landslide prone areas. The second index, or Slope Multiplier Index (SMI), uses individual Landsat data bands and basic Landsat band ratios as environmental proxies to replicate soil, vegetative and hydrologic properties. Both models achieve accuracy over 70% and rival results from more complicated published literature. The accuracy of the indices was assessed with the creation of a landslide inventory developed from field observations occurring in December 2007 and November 2008. The creation of these indices represents an efficient and accurate way of determining landslide susceptibility zonation in data poor areas where environmental protection practitioners may be overextended, under-trained or both.

  20. Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation.

    Science.gov (United States)

    Kraehenmann, Rainer; Pokorny, Dan; Vollenweider, Leonie; Preller, Katrin H; Pokorny, Thomas; Seifritz, Erich; Vollenweider, Franz X

    2017-07-01

    Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming. This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects. Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire. LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin. LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.

  1. Retinitis Pigmentosa.

    Science.gov (United States)

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  2. Retinitis Pigmentosa

    Science.gov (United States)

    ... Linked Retinoschisis (XLRS) X-Linked Retinitis Pigmentosa (XLRP) Usher Syndrome Other Retinal Diseases Glossary News & Research News & Research ... degenerate. Forms of RP and related diseases include Usher syndrome, Leber congenital amaurosis, and Bardet-Biedl syndrome, among ...

  3. Retinal Diseases

    Science.gov (United States)

    ... Linked Retinoschisis (XLRS) X-Linked Retinitis Pigmentosa (XLRP) Usher Syndrome Other Retinal Diseases Glossary News & Research News & Research ... central portion of the retina called the macula. Usher Syndrome Usher syndrome is an inherited condition characterized by ...

  4. Split bundle detection in polarimetric images of the human retinal nerve fiber layer

    NARCIS (Netherlands)

    Vermeer, K. A.; Reus, N. J.; Vos, F. M.; Lemij, H. G.; Vossepoel, A. M.

    2007-01-01

    One method for assessing pathological retinal nerve fiber layer (NFL) appearance is by comparing the NFL to normative values, derived from healthy subjects. These normative values will be more specific when normal physiological differences are taken into account. One common variation is a split

  5. Coupling Retinal Scanning Displays to the Human Visual System: Visual System Response and Engineering Considerations

    National Research Council Canada - National Science Library

    Turner, Stuart

    2002-01-01

    A retinal scanning display (RSD) is a visual display that presents an image to an observer via a modulated beam of light that is directed through the eye's pupil and rapidly scanned in a raster-like pattern across the retina...

  6. Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

    DEFF Research Database (Denmark)

    Fanelli, Giorgia; Gonzalez-Cordero, Anai; Gardner, Peter J

    2017-01-01

    induced-pluripotent stem cell (iPSC)-derived RPE cells, particularly with regard to the complement pathway. We focused on collectin-11 (CL-11), a pattern recognition molecule that can trigger complement activation in renal epithelial tissue. We found evidence of constitutive and hypoxia-induced expression......, failed to activate complement. The presence of CL-11 in healthy murine and human retinal tissues confirmed the biological relevance of CL-11. Our data describe a new trigger mechanism of complement activation that could be important in disease pathogenesis and therapeutic interventions....

  7. Role of macrophage migration inhibitory factor (MIF) in the effects of oxidative stress on human retinal pigment epithelial cells.

    Science.gov (United States)

    Ko, Ji-Ae; Sotani, Yasuyuki; Ibrahim, Diah Gemala; Kiuchi, Yoshiaki

    2017-10-01

    Proliferative vitreoretinopathy (PVR) is the major cause of treatment failure in individuals who undergo surgery for retinal detachment. The epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells contributes to the pathogenesis of PVR. Oxidative stress is thought to play a role in the progression of retinal diseases including PVR. We have now examined the effects of oxidative stress on the EMT and related processes in the human RPE cell line. We found that H 2 O 2 induced the contraction of RPE cells in a three-dimensional collagen gel. Analysis of a cytokine array revealed that H 2 O 2 specifically increased the release of macrophage migration inhibitory factor (MIF) from RPE cells. Reverse transcription-polymerase chain reaction and immunoblot analyses showed that H 2 O 2 increased the expression of MIF in RPE cells. Immunoblot and immunofluorescence analyses revealed that H 2 O 2 upregulated the expression of α-SMA and vimentin and downregulated that of ZO-1 and N-cadherin. Consistent with these observations, the transepithelial electrical resistance of cell was reduced by exposure to H 2 O 2 . The effects of oxidative stress on EMT-related and junctional protein expression as well as on transepithelial electrical resistance were inhibited by antibodies to MIF, but they were not mimicked by treatment with recombinant MIF. Finally, analysis with a profiling array for mitogen-activated protein kinase signalling revealed that H 2 O 2 specifically induced the phosphorylation of p38 mitogen-activated protein kinase. Our results thus suggest that MIF may play a role in induction of the EMT and related processes by oxidative stress in RPE cells and that it might thereby contribute to the pathogenesis of PVR. Proliferative vitreoretinopathy is a major complication of rhegmatogenous retinal detachment, and both oxidative stress and induction of the EMT in RPE cells are thought to contribute to the pathogenesis of this condition. We have now

  8. Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

    OpenAIRE

    Fox, B; Bull, T B; Arden, G B

    1980-01-01

    The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia...

  9. Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa.

    Science.gov (United States)

    Fox, B; Bull, T B; Arden, G B

    1980-01-01

    The electron microscopic structure of cilia from the inferior turbinate of the nose was studied in 12 adults, four with chronic sinusitis, one with allergic rhinitis, two with bronchiectasis, three with deviated nasal septum, and two normals. The changes are compared with those found in nasal cilia in 14 patients with retinitis pigmentosa. There were compound cilia in the seven cases with chronic sinusitis, allergic rhinitis, and bronchiectasis but, apart from this, the structure of the cilia was similar in all 12 cases. There were variations in the microtubular pattern in about 4% of cilia, dynein arms were not seen in 4%, and in the rest an average of 5-6 dynein arms were seen in each cilium. The orientation of the cilia was 0 to 90 degrees. In the retinitis pigmentosa patients there was a highly significant increase in cilial abnormalities. The establishment on a quantitative basis of the variations in normal structure of nasal cilila facilitated the recognition of an association between cilial abnormalities and retinitis pigmentosa and should help in the identification of associations that may exist between cilial abnormalities and other diseases. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 PMID:7400333

  10. Retinal Vasculitis

    Science.gov (United States)

    Rosenbaum, James T.; Sibley, Cailin H.; Lin, Phoebe

    2016-01-01

    Purpose of review Ophthalmologists and rheumatologists frequently miscommunicate in consulting on patients with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent papers on this diagnosis. Recent findings 1) The genetic basis of some rare forms of retinal vascular disease have recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; 2) Behçet’s disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; 3) retinal imaging including fluorescein angiography and other newer imaging modalities has proven crucial to the identification and characterization of retinal vasculitis and its complications; 4) although monoclonal antibodies to IL-17A or IL-1 beta failed in trials for Behçet’s disease, antibodies to TNF alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis. Summary Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet’s disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of non-infectious retinal vasculitis may require alternate therapeutic management. PMID:26945335

  11. Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

    Science.gov (United States)

    Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

    2013-08-01

    Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

  12. The immune privilege of the eye: human retinal pigment epithelial cells selectively modulate T-cell activation in vitro

    DEFF Research Database (Denmark)

    Kaestel, Charlotte G; Lovato, Paola; Ødum, Niels

    2005-01-01

    PURPOSE: To examine the effect of human retinal pigment epithelial (RPE) cells on phytohemagglutinin (PHA) activation of T cells. METHODS: Resting peripheral blood lymphocytes (PBLs) were stimulated with PHA with or without the presence of gamma-irradiated RPE cells. Proliferation and the cell...... in cell culture supernatant was measured by ELISA. RESULTS: Human RPE cells were found to suppress PHA-induced proliferation, cyclin A, IL-2R-alpha and -gamma, and CD71 expression and decrease the production of IL-2; but RPE cells do not inhibit the PHA-induced expression of early activation markers CD69......, MHC class I and II, and of cyclin D of the PBLs. CONCLUSIONS: These results are the first to indicate that RPE cells impede generation of activated T cells by interfering with the induction of high-affinity IL-2R-alphabetagamma, IL-2 production, and the expression of CD71 and cyclin A....

  13. Thiamine and benfotiamine prevent apoptosis induced by high glucose-conditioned extracellular matrix in human retinal pericytes.

    Science.gov (United States)

    Beltramo, Elena; Nizheradze, Konstantin; Berrone, Elena; Tarallo, Sonia; Porta, Massimo

    2009-10-01

    Early and selective loss of pericytes and thickening of the basement membrane are hallmarks of diabetic retinopathy. We reported reduced adhesion, but no changes in apoptosis, of bovine retinal pericytes cultured on extracellular matrix (ECM) produced by endothelial cells in high glucose (HG). Since human and bovine pericytes may behave differently in conditions mimicking the diabetic milieu, we verified the behaviour of human retinal pericytes cultured on HG-conditioned ECM. Pericytes were cultured in physiological/HG on ECM produced by human umbilical vein endothelial cells in physiological/HG, alone or in the presence of thiamine and benfotiamine. Adhesion, proliferation, apoptosis, p53 and Bcl-2/Bax ratio (mRNA levels and protein concentrations) were measured in wild-type and immortalized human pericytes. Both types of pericytes adhered less to HG-conditioned ECM and plastic than to physiological glucose-conditioned ECM. DNA synthesis was impaired in pericytes cultured in HG on the three different surfaces but there were no differences in proliferation. DNA fragmentation and Bcl-2/Bax ratio were greatly enhanced by HG-conditioned ECM in pericytes kept in both physiological and HG. Addition of thiamine and benfotiamine to HG during ECM production completely prevented these damaging effects. Apoptosis is strongly increased in pericytes cultured on ECM produced by endothelium in HG, probably due to impairment of the Bcl-2/Bax ratio. Thiamine and benfotiamine completely revert this effect. This behaviour is therefore completely different from that of bovine pericytes, underlining the importance of establishing species-specific cell models to study the mechanisms of diabetic retinopathy. (c) 2009 John Wiley & Sons, Ltd.

  14. Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution.

    Science.gov (United States)

    Starnes, Austin C; Huisingh, Carrie; McGwin, Gerald; Sloan, Kenneth R; Ablonczy, Zsolt; Smith, R Theodore; Curcio, Christine A; Ach, Thomas

    2016-01-01

    The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.

  15. Retinal vasculitis.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Herbort, Carl P; Tabbara, Khalid F

    2005-12-01

    Retinal vasculitis is a sight-threatening intraocular inflammation affecting the retinal vessels. It may occur as an isolated ocular condition, as a manifestation of infectious or neoplastic disorders, or in association with a systemic inflammatory disease. The search for an underlying etiology should be approached in a multidisciplinary fashion based on a thorough history, review of systems, physical examination, and laboratory evaluation. Discrimination between infectious and noninfectious etiologies of retinal vasculitis is important because their treatment is different. This review is based on recently published articles on retinal vasculitis and deals with its clinical diagnosis, its link with systemic diseases, and its laboratory investigation.

  16. Construction of a cDNA library from human retinal pigment epithelial cells challenged with rod outer segments.

    Science.gov (United States)

    Cavaney, D M; Rakoczy, P E; Constable, I J

    1995-05-01

    To study genes expressed by retinal pigment epithelial (RPE) cells during phagocytosis and digestion of rod outer segments (ROS), a complementary (c)DNA library was produced using an in-vitro model. The cDNA library can be used to study molecular changes which contribute to the development of diseases due to a failure in outer segment phagocytosis and digestion by RPE cells. Here we demonstrate a way to study genes and their functions using a molecular biological approach and describing the first step involved in this process, the construction of a cDNA library. Human RPE cells obtained from the eyes of a seven-year-old donor were cultured and challenged with bovine ROS. The culture was harvested and total RNA was extracted. Complementary DNA was transcribed from the messenger (m)RNA and was directionally cloned into the LambdaGEM-4 bacteriophage vector successfully. Some clones were picked and the DNA extracted, to determine the size of the inserts as a measure of the quality of the library. Molecular biology and cell culture are important tools to be used in eye research, especially in areas where tissue is limiting and animal models are not available. We now have a ROS challenged RPE cDNA library which will be used to identify genes responsible for degrading phagocytosed debris within the retinal pigment epithelium.

  17. 2-ethylpyridine, a cigarette smoke component, causes mitochondrial damage in human retinal pigment epithelial cells in vitro

    Directory of Open Access Journals (Sweden)

    S Mansoor

    2014-01-01

    Full Text Available Purpose: Our goal was to identify the cellular and molecular effects of 2-ethylpyridine (2-EP, a component of cigarette smoke on human retinal pigment epithelial cells (ARPE-19 in vitro. Materials and Methods: ARPE-19 cells were exposed to varying concentrations of 2-EP. Cell viability (CV was measured by a trypan blue dye exclusion assay. Caspase-3/7 and caspase-9 activities were measured by fluorochrome assays. The production of reactive oxygen/nitrogen species (ROS/RNS was detected with a 2′,7′-dichlorodihydrofluorescein diacetate dye assay. The JC-1 assay was used to measure mitochondrial membrane potential (ΔΨm. Mitochondrial redox potential was measured using a RedoxSensor Red kit and mitochondria were evaluated with Mitotracker dye. Results: After 2-EP exposure, ARPE-19 cells showed significantly decreased CV, increased caspase-3/7 and caspase-9 activities, elevated ROS/RNS levels, decreased ΔΨm value and decreased redox fluorescence when compared with control samples. Conclusions: These results show that 2-EP treatment induced cell death by caspase-dependent apoptosis associated with an oxidative stress and mitochondrial dysfunction. These data represent a possible mechanism by which smoking contributes to age-related macular degeneration and other retinal diseases and identify mitochondria as a target for future therapeutic interventions.

  18. Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications.

    Science.gov (United States)

    Holmes, Emily A; Blackwell, Simon E; Burnett Heyes, Stephanie; Renner, Fritz; Raes, Filip

    2016-01-01

    Mental imagery is an experience like perception in the absence of a percept. It is a ubiquitous feature of human cognition, yet it has been relatively neglected in the etiology, maintenance, and treatment of depression. Imagery abnormalities in depression include an excess of intrusive negative mental imagery; impoverished positive imagery; bias for observer perspective imagery; and overgeneral memory, in which specific imagery is lacking. We consider the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions. Treatment advances capitalizing on the representational format of imagery (as opposed to its content) are reviewed, including imagery rescripting, positive imagery generation, and memory specificity training. Consideration of mental imagery can contribute to clinical assessment and imagery-focused psychological therapeutic techniques and promote investigation of underlying mechanisms for treatment innovation. Research into mental imagery in depression is at an early stage. Work that bridges clinical psychology and neuroscience in the investigation of imagery-related mechanisms is recommended.

  19. Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz

    2015-01-01

    Human retinal pigment epithelial (hRPE) cell implants into the striatum have been investigated as a potential cell-based treatment for Parkinson's disease in a Phase II clinical trial that recently failed. We hypothesize that the trophic factor potential of the hRPE cells could potentially influe...

  20. Advances In very high resolution satellite imagery analysis for Monitoring human settlements

    Energy Technology Data Exchange (ETDEWEB)

    Vatsavai, Raju [ORNL; Cheriyadat, Anil M [ORNL; Bhaduri, Budhendra L [ORNL

    2014-01-01

    The high rate of urbanization, political conflicts and ensuing internal displacement of population, and increased poverty in the 20th century has resulted in rapid increase of informal settlements. These unplanned, unauthorized, and/or unstructured homes, known as informal settlements, shantytowns, barrios, or slums, pose several challenges to the nations, as these settlements are often located in most hazardous regions and lack basic services. Though several World Bank and United Nations sponsored studies stress the importance of poverty maps in designing better policies and interventions, mapping slums of the world is a daunting and challenging task. In this paper, we summarize our ongoing research on settlement mapping through the utilization of Very high resolution (VHR) remote sensing imagery. Most existing approaches used to classify VHR images are single instance (or pixel-based) learning algorithms, which are inadequate for analyzing VHR imagery, as single pixels do not contain sufficient contextual information (see Figure 1). However, much needed spatial contextual information can be captured via feature extraction and/or through newer machine learning algorithms in order to extract complex spatial patterns that distinguish informal settlements from formal ones. In recent years, we made significant progress in advancing the state of art in both directions. This paper summarizes these results.

  1. Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies

    Science.gov (United States)

    Riera, Marina; Fontrodona, Laura; Albert, Silvia; Ramirez, Diana Mora; Seriola, Anna; Salas, Anna; Muñoz, Yolanda; Ramos, David; Villegas-Perez, Maria Paz; Zapata, Miguel Angel; Raya, Angel; Ruberte, Jesus; Veiga, Anna; Garcia-Arumi, Jose

    2016-01-01

    Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD. PMID:27006969

  2. Comparative study of human embryonic stem cells (hESC and human induced pluripotent stem cells (hiPSC as a treatment for retinal dystrophies

    Directory of Open Access Journals (Sweden)

    Marina Riera

    2016-01-01

    Full Text Available Retinal dystrophies (RD are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC-based therapies. We differentiated RPE from human embryonic stem cells (hESCs or human-induced pluripotent stem cells (hiPSCs and transplanted them into the subretinal space of the Royal College of Surgeons (RCS rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD.

  3. Protective Effects of Blueberry Anthocyanins against H2O2-Induced Oxidative Injuries in Human Retinal Pigment Epithelial Cells.

    Science.gov (United States)

    Huang, Wu-Yang; Wu, Han; Li, Da-Jing; Song, Jiang-Feng; Xiao, Ya-Dong; Liu, Chun-Quan; Zhou, Jian-Zhong; Sui, Zhong-Quan

    2018-02-21

    Blueberry anthocyanins are considered protective of eye health because of their recognized antioxidant properties. In this study, blueberry anthocyanin extract (BAE), malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal) all reduced H 2 O 2 -induced oxidative stress by decreasing the levels of reactive oxygen species and malondialdehyde and increasing the levels of superoxide dismutase, catalase, and glutathione peroxidase in human retinal pigment epithelial cells. BAE and the anthocyanin standards enhanced cell viability from 63.69 ± 3.36 to 86.57 ± 6.92% (BAE), 115.72 ± 23.41% (Mv), 98.15 ± 9.39% (Mv-3-glc), and 127.97 ± 20.09% (Mv-3-gal) and significantly inhibited cell apoptosis (P blueberry anthocyanins could inhibit the induction and progression of age-related macular degeneration (AMD) through antioxidant mechanisms.

  4. In vitro differentiation of adipose-tissue-derived mesenchymal stem cells into neural retinal cells through expression of human PAX6 (5a) gene.

    Science.gov (United States)

    Rezanejad, Habib; Soheili, Zahra-Soheila; Haddad, Farhang; Matin, Maryam M; Samiei, Shahram; Manafi, Ali; Ahmadieh, Hamid

    2014-04-01

    The neural retina is subjected to various degenerative conditions. Regenerative stem-cell-based therapy holds great promise for treating severe retinal degeneration diseases, although many drawbacks remain to be overcome. One important problem is to gain authentically differentiated cells for replacement. Paired box 6 protein (5a) (PAX6 (5a)) is a highly conserved master control gene that has an essential role in the development of the vertebrate visual system. Human adipose-tissue-derived stem cell (hADSC) isolation was performed by using fat tissues and was confirmed by the differentiation potential of the cells into adipocytes and osteocytes and by their surface marker profile. The coding region of the human PAX6 (5a) gene isoform was cloned and lentiviral particles were propagated in HEK293T. The differentiation of hADSCs into retinal cells was characterized by morphological characteristics, quantitative real-time reverse transcription plus the polymerase chain reaction (qPCR) and immunocytochemistry (ICC) for some retinal cell-specific and retinal pigmented epithelial (RPE) cell-specific markers. hADSCs were successfully isolated. Flow cytometric analysis of surface markers indicated the high purity (~97 %) of isolated hADSCs. After 30 h of post-transduction, cells gradually showed the characteristic morphology of neuronal cells and small axon-like processes emerged. qPCR and ICC confirmed the differentiation of some neural retinal cells and RPE cells. Thus, PAX6 (5a) transcription factor expression, together with medium supplemented with fibronectin, is able to induce the differentiation of hADSCs into retinal progenitors, RPE cells and photoreceptors.

  5. Imagery Integration Team

    Science.gov (United States)

    Calhoun, Tracy; Melendrez, Dave

    2014-01-01

    The Human Exploration Science Office (KX) provides leadership for NASA's Imagery Integration (Integration 2) Team, an affiliation of experts in the use of engineering-class imagery intended to monitor the performance of launch vehicles and crewed spacecraft in flight. Typical engineering imagery assessments include studying and characterizing the liftoff and ascent debris environments; launch vehicle and propulsion element performance; in-flight activities; and entry, landing, and recovery operations. Integration 2 support has been provided not only for U.S. Government spaceflight (e.g., Space Shuttle, Ares I-X) but also for commercial launch providers, such as Space Exploration Technologies Corporation (SpaceX) and Orbital Sciences Corporation, servicing the International Space Station. The NASA Integration 2 Team is composed of imagery integration specialists from JSC, the Marshall Space Flight Center (MSFC), and the Kennedy Space Center (KSC), who have access to a vast pool of experience and capabilities related to program integration, deployment and management of imagery assets, imagery data management, and photogrammetric analysis. The Integration 2 team is currently providing integration services to commercial demonstration flights, Exploration Flight Test-1 (EFT-1), and the Space Launch System (SLS)-based Exploration Missions (EM)-1 and EM-2. EM-2 will be the first attempt to fly a piloted mission with the Orion spacecraft. The Integration 2 Team provides the customer (both commercial and Government) with access to a wide array of imagery options - ground-based, airborne, seaborne, or vehicle-based - that are available through the Government and commercial vendors. The team guides the customer in assembling the appropriate complement of imagery acquisition assets at the customer's facilities, minimizing costs associated with market research and the risk of purchasing inadequate assets. The NASA Integration 2 capability simplifies the process of securing one

  6. Survival Improvement in Human Retinal Pigment Epithelial Cells via Fas Receptor Targeting by miR-374a.

    Science.gov (United States)

    Tasharrofi, Nooshin; Kouhkan, Fatemeh; Soleimani, Masoud; Soheili, Zahra-Sheila; Kabiri, Mahboubeh; Mahmoudi Saber, Mohaddeseh; Dorkoosh, Farid Abedin

    2017-12-01

    Oxidative conditions of the eye could contribute to retinal cells loss through activating the Fas-L/Fas pathway. This phenomenon is one of the leading causes of some ocular diseases like age-related macular degeneration (AMD). By targeting proteins at their mRNA level, microRNAs (miRNAs) can regulate gene expression and cell function. The aim of the present study is to investigate Fas targeting by miR-374a and find whether it can inhibit Fas-mediated apoptosis in primary human retinal pigment epithelial (RPE) cells under oxidative stress. So, the primary human RPE cells were transfected with pre-miR-374a pLEX construct using polymeric carrier and were exposed to H 2 O 2 (200 μM) as an oxidant agent for induction of Fas expression. Fas expression at mRNA and protein level was evaluated by quantitative real-time PCR and Western blot analysis, respectively. These results revealed that miR-374a could prevent Fas upregulation under oxidative conditions. Moreover, Luciferase activity assay confirmed that Fas could be a direct target of miR-374a. The cell viability studies demonstrated that caspase-3 activity was negligible in miR-374a treated cells compared to the controls. Our data suggest miR-374a is a negative regulator of Fas death receptor which is able to enhance the cell survival and protect RPE cells against oxidative conditions. J. Cell. Biochem. 118: 4854-4861, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. N-Acetylcysteine Amide Protects Against Oxidative Stress–Induced Microparticle Release From Human Retinal Pigment Epithelial Cells

    Science.gov (United States)

    Carver, Kyle A.; Yang, Dongli

    2016-01-01

    Purpose Oxidative stress is a major factor involved in retinal pigment epithelium (RPE) apoptosis that underlies AMD. Drusen, extracellular lipid- and protein-containing deposits, are strongly associated with the development of AMD. Cell-derived microparticles (MPs) are small membrane-bound vesicles shed from cells. The purpose of this study was to determine if oxidative stress drives MP release from RPE cells, to assess whether these MPs carry membrane complement regulatory proteins (mCRPs: CD46, CD55, and CD59), and to evaluate the effects of a thiol antioxidant on oxidative stress–induced MP release. Methods Retinal pigment epithelium cells isolated from human donor eyes were cultured and treated with hydrogen peroxide (H2O2) to induce oxidative stress. Isolated MPs were fixed for transmission electron microscopy or processed for component analysis by flow cytometry, Western blot analysis, and confocal microscopy. Results Transmission electron microscopy showed that MPs ranged in diameter from 100 to 1000 nm. H2O2 treatment led to time- and dose-dependent elevations in MPs with externalized phosphatidylserine and phosphatidylethanolamine, known markers of MPs. These increases were strongly correlated to RPE apoptosis. Oxidative stress significantly increased the release of mCRP-positive MPs, which were prevented by a thiol antioxidant, N-acetylcysteine amide (NACA). Conclusions This is the first evidence that oxidative stress induces cultured human RPE cells to release MPs that carry mCRPs on their surface. The levels of released MPs are strongly correlated with RPE apoptosis. N-acetylcysteine amide prevents oxidative stress–induced effects. Our findings indicate that oxidative stress reduces mCRPs on the RPE surface through releasing MPs. PMID:26842754

  8. Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells

    International Nuclear Information System (INIS)

    Bridges, Christy C.; Battle, Jamie R.; Zalups, Rudolfs K.

    2007-01-01

    Inorganic mercury (Hg 2+ ) is a prevalent environmental contaminant to which exposure to can damage rod photoreceptor cells and compromise scotopic vision. The retinal pigment epithelium (RPE) likely plays a role in the ocular toxicity associated with Hg 2+ exposure in that it mediates transport of substances to the photoreceptor cells. In order for Hg 2+ to access photoreceptor cells, it must first be taken up by the RPE, possibly by mechanisms involving transporters of essential nutrients. In other epithelia, Hg 2+ , when conjugated to cysteine (Cys) or homocysteine (Hcy), gains access to the intracellular compartment of the target cells via amino acid and organic anion transporters. Accordingly, the purpose of the current study was to test the hypothesis that Cys and Hcy S-conjugates of Hg 2+ utilize amino acid transporters to gain access into RPE cells. Time- and temperature-dependence, saturation kinetics, and substrate-specificity of the transport of Hg 2+ , was assessed in ARPE-19 cells exposed to the following S-conjugates of Hg 2+ : Cys (Cys-S-Hg-S-Cys), Hcy (Hcy-S-Hg-S-Hcy), N-acetylcysteine (NAC-S-Hg-S-NAC) or glutathione (GSH-S-Hg-S-GSH). We discovered that only Cys-S-Hg-S-Cys and Hcy-S-Hg-S-Hcy were taken up by these cells. This transport was Na + -dependent and was inhibited by neutral and cationic amino acids. RT-PCR analyses identified systems B 0,+ and ASC in ARPE-19 cells. Overall, our data suggest that Cys-S-Hg-S-Cys and Hcy-S-Hg-S-Hcy are taken up into ARPE-19 cells by Na-dependent amino acid transporters, possibly systems B 0,+ and ASC. These amino acid transporters may play a role in the retinal toxicity observed following exposure to mercury

  9. Blue-light filtering alters angiogenic signaling in human retinal pigmented epithelial cells culture model.

    Science.gov (United States)

    Vila, Natalia; Siblini, Aya; Esposito, Evangelina; Bravo-Filho, Vasco; Zoroquiain, Pablo; Aldrees, Sultan; Logan, Patrick; Arias, Lluis; Burnier, Miguel N

    2017-11-02

    Light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD. Three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines. A significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions. Following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein

  10. TRANSPORT OF THIOL-CONJUGATES OF INORGANIC MERCURY IN HUMAN RETINAL PIGMENT EPITHELIAL CELLS

    Science.gov (United States)

    Bridges, Christy C.; Battle, Jamie R.; Zalups, Rudolfs K.

    2007-01-01

    Inorganic mercury (Hg2+) is a prevalent environmental contaminant to which exposure to can damage rod photoreceptor cells and compromise scotopic vision. The retinal pigment epithelium (RPE) likely plays a role in the ocular toxicity associated with Hg2+ exposure in that it mediates transport of substances to the photoreceptor cells. In order for Hg2+ to access photoreceptor cells, it must be first be taken up by the RPE, possibly by mechanisms involving transporters of essential nutrients. In other epithelia, Hg2+, when conjugated to cysteine (Cys) or homocysteine (Hcy), gains access to the intracellular compartment of the target cells via amino acid and organic anion transporters. Accordingly, the purpose of the current study was to test the hypothesis that Cys and Hcy S-conjugates of Hg2+ utilize amino acid transporters to gain access into RPE cells. Time- and temperature-dependence, saturation kinetics, and substrate-specificity of the transport of Hg2+, was assessed in ARPE-19 cells exposed to the following S-conjugates of Hg2+: Cys (Cys-S-Hg-S-Cys), Hcy (Hcy-S-Hg-S-Hcy), N-acetylcysteine (NAC-S-Hg-S-NAC) or glutathione (GSH-S-Hg-S-GSH). We discovered that only Cys-S-Hg-S-Cys and Hcy-S-Hg-S-Hcy were taken up by these cells. This transport was Na+-dependent and was inhibited by neutral and cationic amino acids. RT-PCR analyses identified systems B0,+ and ASC in ARPE-19 cells. Overall, our data suggest that Cys-S-Hg-S-Cys and Hcy-S-Hg-S-Hcy are taken up into ARPE-19 cells by Na-dependent amino acid transporters, possibly systems B0,+ and ASC. These amino acid transporters may play a role in the retinal toxicity observed following exposure to mercury. PMID:17467761

  11. Interferon-gamma (IFN-γ-mediated retinal ganglion cell death in human tyrosinase T cell receptor transgenic mouse.

    Directory of Open Access Journals (Sweden)

    Shahid Husain

    Full Text Available We have recently demonstrated the characterization of human tyrosinase TCR bearing h3T-A2 transgenic mouse model, which exhibits spontaneous autoimmune vitiligo and retinal dysfunction. The purpose of current study was to determine the role of T cells and IFN-γ in retina dysfunction and retinal ganglion cell (RGC death using this model. RGC function was measured by pattern electroretinograms (ERGs in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Expression of CD3, IFN-γ, GFAP, and caspases was measured by immunohistochemistry and Western blotting. All functional and structural changes were measured in 12-month-old h3T-A2 mice and compared with age-matched HLA-A2 wild-type mice. Both pattern-ERGs (42%, p = 0.03 and RGC numbers (37%, p = 0.0001 were reduced in h3T-A2 mice when compared with wild-type mice. The level of CD3 expression was increased in h3T-A2 mice (h3T-A2: 174 ± 27% vs. HLA-A2: 100%; p = 0.04. The levels of effector cytokine IFN-γ were also increased significantly in h3T-A2 mice (h3T-A2: 189 ± 11% vs. HLA-A2: 100%; p = 0.023. Both CD3 and IFN-γ immunostaining were increased in nerve fiber (NF and RGC layers of h3T-A2 mice. In addition, we have seen a robust increase in GFAP staining in h3T-A2 mice (mainly localized to NF layer, which was substantially reduced in IFN-γ ((-/- knockout h3T-A2 mice. We also have seen an up-regulation of caspase-3 and -9 in h3T-A2 mice. Based on our data we conclude that h3T-A2 transgenic mice exhibit visual defects that are mostly associated with the inner retinal layers and RGC function. This novel h3T-A2 transgenic mouse model provides opportunity to understand RGC pathology and test neuroprotective strategies to rescue RGCs.

  12. MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tagami, Mizuki [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Kusuhara, Sentaro, E-mail: kusu@med.kobe-u.ac.jp [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Imai, Hisanori [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Uemura, Akiyoshi [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Department of Vascular Biology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Honda, Shigeru; Tsukahara, Yasutomo; Negi, Akira [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-10-01

    Research highlights: {yields} Exogenous VEGF decreases MRP4 expression in a dose-dependent manner. {yields} MRP4 knockdown leads to enhanced cell migration. {yields} MRP4 knockdown suppresses caspase-3-mediated cell apoptosis. {yields} MRP4 knockdown produces cell assembly and cell aggregation. -- Abstract: The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.

  13. Role for nectin-1 in herpes simplex virus 1 entry and spread in human retinal pigment epithelial cells

    Science.gov (United States)

    Tiwari, Vaibhav; Oh, Myung-Jin; Kovacs, Maria; Shukla, Shripaad Y.; Valyi-Nagy, Tibor; Shukla, Deepak

    2009-01-01

    Herpes simplex virus 1 (HSV-1) demonstrates a unique ability to infect a variety of host cell types. Retinal pigment epithelial (RPE) cells form the outermost layer of the retina and provide a potential target for viral invasion and permanent vision impairment. Here we examine the initial cellular and molecular mechanisms that facilitate HSV-1 invasion of human RPE cells. High-resolution confocal microscopy demonstrated initial interaction of green fluorescent protein (GFP)-tagged virions with filopodia-like structures present on cell surfaces. Unidirectional movement of the virions on filopodia to the cell body was detected by live cell imaging of RPE cells, which demonstrated susceptibility to pH-dependent HSV-1 entry and replication. Use of RT-PCR indicated expression of nectin-1, herpes virus entry mediator (HVEM) and 3-O-sulfotransferase-3 (as a surrogate marker for 3-O-sulfated heparan sulfate). HVEM and nectin-1 expression was subsequently verified by flow cytometry. Nectin-1 expression in murine retinal tissue was also demonstrated by immunohistochemistry. Antibodies against nectin-1, but not HVEM, were able to block HSV-1 infection. Similar blocking effects were seen with a small interfering RNA construct specifically directed against nectin-1, which also blocked RPE cell fusion with HSV-1 glycoprotein-expressing Chinese hamster ovary (CHO-K1) cells. Anti-nectin-1 antibodies and F-actin depolymerizers were also successful in blocking the cytoskeletal changes that occur upon HSV-1 entry into cells. Our findings shed new light on the cellular and molecular mechanisms that help the virus to enter the cells of the inner eye. PMID:18803666

  14. Human pericyte-endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment.

    Science.gov (United States)

    Tarallo, Sonia; Beltramo, Elena; Berrone, Elena; Porta, Massimo

    2012-12-01

    Pericytes regulate vascular tone, perfusion pressure and endothelial cell (EC) proliferation in capillaries. Thiamine and benfotiamine counteract high glucose-induced damage in vascular cells. We standardized two human retinal pericyte (HRP)/EC co-culture models to mimic the diabetic retinal microvascular environment. We aimed at evaluating the interactions between co-cultured HRP and EC in terms of proliferation/apoptosis and the possible protective role of thiamine and benfotiamine against high glucose-induced damage. EC and HRP were co-cultured in physiological glucose and stable or intermittent high glucose, with or without thiamine/benfotiamine. No-contact model: EC were plated on a porous membrane suspended into the medium and HRP on the bottom of the same well. Cell-to-cell contact model: EC and HRP were plated on the opposite sides of the same membrane. Proliferation (cell counts and DNA synthesis), apoptosis and tubule formation in Matrigel were assessed. In the no-contact model, stable high glucose reduced proliferation of co-cultured EC/HRP and EC alone and increased co-cultured EC/HRP apoptosis. In the contact model, both stable and intermittent high glucose reduced co-cultured EC/HRP proliferation and increased apoptosis. Stable high glucose had no effects on HRP in separate cultures. Both EC and HRP proliferated better when co-cultured. Thiamine and benfotiamine reversed high glucose-induced damage in all cases. HRP are sensitive to soluble factors released by EC when cultured in high glucose conditions, as suggested by conditioned media assays. In the Matrigel models, addition of thiamine and benfotiamine re-established the high glucose-damaged interactions between EC/HRP and stabilized microtubules.

  15. Evidence of Flicker-Induced Functional Hyperaemia in the Smallest Vessels of the Human Retinal Blood Supply.

    Directory of Open Access Journals (Sweden)

    Angelina Duan

    Full Text Available Regional changes in blood flow are initiated within neural tissue to help fuel local differences in neural activity. Classically, this response was thought to arise only in larger arterioles and venules. However, recently, it has been proposed that a the smallest vessels of the circulation make a comparable contribution, and b the response should be localised intermittently along such vessels, due to the known distribution of contractile mural cells. To assess these hypotheses in human neural tissue in vivo, we imaged the retinal microvasculature (diameters 3-28 μm non-invasively, using adaptive optics, before and after delivery of focal (360 μm patches of flickering visible light. Our results demonstrated a definite average response in 35% of all vessel segments analysed. In these responding vessels, the magnitude of proportional dilation (mean ± SEM for pre-capillary arterioles 13 ± 5%, capillaries 31 ± 8%, and post-capillary venules 10 ± 3% is generally far greater than the magnitudes we and others have measured in the larger retinal vessels, supporting proposition a above. The dilations observed in venules were unexpected based on previous animal work, and may be attributed either to differences in stimulus or species. Response heterogeneity across the network was high; responses were also heterogeneous along individual vessels (45% of vessel segments showed demonstrable locality in their response. These observations support proposition b above. We also observed a definite average constriction across 7% of vessel segments (mean ± SEM constriction for capillaries -16 ± 3.2%, and post-capillary venules -18 ± 12%, which paints a picture of dynamic redistribution of flow throughout the smallest vessel networks in the retina in response to local, stimulus-driven metabolic demand.

  16. Noninvasive Retinal Markers in Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Blindbæk, Søren Leer; Torp, Thomas Lee; Lundberg, Kristian

    2017-01-01

    The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber...... and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only...... retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long...

  17. Chaetomium retinitis.

    Science.gov (United States)

    Tabbara, Khalid F; Wedin, Keith; Al Haddab, Saad

    2010-01-01

    To report a case of Chaetomium atrobrunneum retinitis in a patient with Hodgkin lymphoma. We studied the ocular manifestations of an 11-year-old boy with retinitis. Biomicroscopy, ophthalmoscopy, and fundus photography were done. Magnetic resonance imaging of the brain was performed. A vitreous biopsy was subjected to viral, bacterial, and fungal cultures. Vitreous culture grew C. atrobrunneum. Magnetic resonance imaging showed multiple cerebral lesions consistent with an infectious process. The patient was given intravenous voriconazole and showed improvement of the ocular and central nervous system lesions. We report a case of central nervous system and ocular lesions by C. atrobrunneum. The retinitis was initially misdiagnosed as cytomegaloviral retinitis. Vitreous biopsy helped in the early diagnosis and prompt treatment of a life- and vision-threatening infection.

  18. Retinitis pigmentosa

    Science.gov (United States)

    ... treatments for retinitis pigmentosa, including the use of DHA, which is an omega-3 fatty acid. Other ... Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 630. ...

  19. Cytomegalovirus retinitis

    Science.gov (United States)

    ... have weakened immune systems as a result of: HIV/AIDS Bone marrow transplant Chemotherapy Drugs that suppress the immune system Organ transplant Symptoms Some people with CMV retinitis have no symptoms. ...

  20. Retinal Detachment

    Science.gov (United States)

    ... to your brain. It provides the sharp, central vision needed for reading, driving, and seeing fine detail. A retinal detachment lifts or pulls the retina from its normal position. It can occur at ...

  1. Influence of ultraviolet A radiation on osmolytes transport in human retinal pigment epithelial cells

    Directory of Open Access Journals (Sweden)

    Da-Yang Wu

    2014-04-01

    Full Text Available AIM: To demonstrate that ultraviolet A(UVAinduces osmolytes accumulation in retinal pigment epithelial(RPEcells.METHODS: Under different experimental conditions such as UVA exposure, hyperosmotic stress condition and hypoosmotic stress condition, RPE cells were cultured for different time periods. The betaine /γ-amino- n-butyric acid(GABAtransporter, the sodium-dependent myoinositol transporter and the taurine transporter(TAUTmRNA were measured by quantitative PCR. The radioactive labeled osmolytes were measured to evaluate the level of osmolytes transportation. RESULTS: This study demonstrated that RPE expressed mRNA specific for the betaine/GABA transporter, for the sodium-dependent myoinositol transporter and for the TAUT. In comparison to norm osmotic(300mosmol/Lcontrols, a 3-5-fold induction of mRNA expression for the betaine/GABA transporter, the sodium-dependent myoinositol transporter and the TAUT was observed within 6-24h after hyperosmotic exposure(400mosmol/L. Expression of osmolyte transporters was associated with an increased uptake of radioactive labeled osmolytes. Conversely, hypoosmotic(200mosmol/Lstimulation induced significant efflux of these osmolytes. UVA significantly stimulated osmolyte uptake. Increased osmolyte uptake was associated with upregulation of mRNA steady-state levels for osmolyte transporters in irradiated cells.CONCLUSION: UVA induces osmolyte uptake in RPE. It is similar reaction to hyperosmotic stress. This suggests that osmolyte uptake response by UVA may be important to maintain homeostasis.

  2. Bioelectronic retinal prosthesis

    Science.gov (United States)

    Weiland, James D.

    2016-05-01

    Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.

  3. Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.

    Science.gov (United States)

    Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

    2014-12-01

    Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

  4. Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 24-Hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser Light and 1064 nm, 170 ps Pulsed Laser Light 12-Hours Post-Exposure: Results Compendium

    National Research Council Canada - National Science Library

    Obringer, John

    2004-01-01

    .... We assessed the sublethal insult to human retinal pigment epithelial cells using a cadaver organ donor explant system for genes differentially expressed 12 and 24 hours post- exposure using gene...

  5. Imagery Data Base Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Imagery Data Base Facility supports AFRL and other government organizations by providing imagery interpretation and analysis to users for data selection, imagery...

  6. Spectral Detection of Human Skin in VIS-SWIR Hyperspectral Imagery without Radiometric Calibration

    Science.gov (United States)

    2012-03-01

    6 Spectral reflectance of human skin at VIS-SWIR wavelengths. Skin with less melanin appears brighter because it has higher reflectance...6 illustrates the spectral reflectance of human skin with different melanin levels. One paper proposes a Normalized Difference Skin Index (NDSI), a...1.4% Melanin 12.6% Melanin 23.2% Melanin 34.3% Melanin 45% Melanin Figure 6. Spectral reflectance of human skin at VIS-SWIR wavelengths. Skin with less

  7. Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

    Science.gov (United States)

    Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

    2013-01-01

    Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

  8. Efficient gene delivery to primary human retinal pigment epithelial cells: The innate and acquired properties of vectors.

    Science.gov (United States)

    Tasharrofi, Nooshin; Kouhkan, Fatemeh; Soleimani, Masoud; Soheili, Zahra-Soheila; Atyabi, Fatemeh; Akbari Javar, Hamid; Abedin Dorkoosh, Farid

    2017-02-25

    The purpose of this study is designing non-viral gene delivery vectors for transfection of the primary human retinal pigment epithelial cells (RPE). In the design process of gene delivery vectors, considering physicochemical properties of vectors alone does not seem to be enough since they interact with constituents of the surrounding environment and hence gain new characteristics. Moreover, due to these interactions, their cargo can be released untimely or undergo degradation before reaching to the target cells. Further, the characteristics of cells itself can also influence the transfection efficacy. For example, the non-dividing property of RPE cells can impede the transfection efficiency which in most studies was ignored by using immortal cell lines. In this study, vectors with different characteristics differing in mixing orders of pDNA, PEI polymer, and PLGA/PEI or PLGA nanoparticles were prepared and characterized. Then, their characteristics and efficacy in gene delivery to RPE cells in the presence of vitreous or fetal bovine serum (FBS) were evaluated. All formulations showed no cytotoxicity and were able to protect pDNA from premature release and degradation in extracellular media. Also, the adsorption of vitreous or serum proteins onto the surface of vectors changed their properties and hence cellular uptake and transfection efficacy. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis

    Science.gov (United States)

    Ashtari, Manzar; Zhang, Hui; Cook, Philip A.; Cyckowski, Laura L.; Shindler, Kenneth S.; Marshall, Kathleen A.; Aravand, Puya; Vossough, Arastoo; Gee, James C.; Maguire, Albert M.; Baker, Chris I.; Bennett, Jean

    2015-01-01

    Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber’s congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. PMID:26180100

  10. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

    Science.gov (United States)

    Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

    2015-01-01

    Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

  11. The MTT assays of bovine retinal pericytes and human microvascular endothelial cells on DLC and Si-DLC-coated TCPS.

    Science.gov (United States)

    Okpalugo, T I T; McKenna, E; Magee, A C; McLaughlin, J; Brown, N M D

    2004-11-01

    MTT (Tetrazolium)-assay suggests that diamond-like carbon (DLC) and silicon-doped DLC (Si-DLC) films obtained under appropriate deposition parameters are not toxic to bovine retinal pericytes, and human microvascular endothelial cells (HMEC). The observed frequency distributions of the optical density (OD) values indicative of cell viability are near Gaussian-normal distribution. One-way ANOVA indicates that at 0.05 levels the population means are not significantly different for the coated and control samples. The observed OD values depend on the cell line (cell growth/metabolic rate), possibly cell cycle stage, the deposition parameters-bias voltage, ion energy, pressure, argon precleaning, and the dopant. For colored thin films like DLC with room temperature photoconductivity and photoelectric effects, it is important to account for the OD contribution from the coating itself. MTT assay, not surprisingly, seems not to be highly sensitive to interfacial cellular interaction resulting from the change in the film's nanostructure, because the tetrazolium metabolism is mainly intracellular and not interfacial. The thin films were synthesized by 13.56 MHz RF-PECVD using argon and acetylene as source gases, with tetramethylsilane (TMS) vapor introduced for silicon doping. This study could be relevant to biomedical application of the films in the eye, peri-vascular, vascular compartments, and for cell-tissue engineering. (c) 2004 Wiley Periodicals, Inc.

  12. C-terminal truncations in human 3 '-5 ' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy

    NARCIS (Netherlands)

    Richards, Anna; van den Maagdenberg, Arn M. J. M.; Jen, Joanna C.; Kavanagh, David; Bertram, Paula; Spitzer, Dirk; Liszewski, M. Kathryn; Barilla-LaBarca, Maria-Louise; Terwindt, Gisela M.; Kasai, Yumi; McLellan, Mike; Grand, Mark Gilbert; Vanmolkot, Kaate R. J.; de Vries, Boukje; Wan, Jijun; Kane, Michael J.; Mamsa, Hafsa; Schaefer, Ruth; Stam, Anine H.; Haan, Joost; Paulus, T. V. M. de Jong; Storimans, Caroline W.; van Schooneveld, Mary J.; Oosterhuis, Jendo A.; Gschwendter, Andreas; Dichgans, Martin; Kotschet, Katya E.; Hodgkinson, Suzanne; Hardy, Todd A.; Delatycki, Martin B.; Hajj-Ali, Rula A.; Kothari, Parul H.; Nelson, Stanley F.; Frants, Rune R.; Baloh, Robert W.; Ferrari, Michel D.; Atkinson, John P.

    Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease

  13. Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.

    Science.gov (United States)

    el-Amraoui, A; Sahly, I; Picaud, S; Sahel, J; Abitbol, M; Petit, C

    1996-08-01

    Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks.

  14. Humoral and cell-mediated immune response against human retinal antigens in relation to ocular onchocerciasis

    NARCIS (Netherlands)

    van der Lelij, A.; Rothova, A.; Stilma, J. S.; Vetter, J. C.; Hoekzema, R.; Kijlstra, A.

    1990-01-01

    Autoimmune mechanisms are thought to be involved in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. The humoral autoimmune response was determined by measuring serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid binding protein

  15. The influences of purple sweet potato anthocyanin on the growth characteristics of human retinal pigment epithelial cells

    Directory of Open Access Journals (Sweden)

    Min Sun

    2015-06-01

    Full Text Available Background: Anthocyanins have been proven to be beneficial to the eyes. However, information is scarce about the effects of purple sweet potato (Ipomoea batatas, L. anthocyanin (PSPA, a class of anthocyanins derived from purple sweet potato roots, on visual health. Objective: The aim of this study was to investigate whether PSPA could have influences on the growth characteristics (cellular morphology, survival, and proliferation of human retinal pigment epithelial (RPE cells, which perform essential functions for the visual process. Methods: The RPE cell line D407 was used in the present study. The cytotoxicity of PSPA was assessed by MTT assay. Then, cellular morphology, viability, cell cycle, Ki67expression, and PI3K/MAPK activation of RPE cells treated with PSPA were determined. Results: PSPA exhibited dose-dependent promotion of RPE cell proliferation at concentrations ranging from 10 to 1,000 µg/ml. RPE cells treated with PSPA demonstrated a predominantly polygonal morphology in a mosaic arrangement, and colony-like cells displayed numerous short apical microvilli and typical ultrastructure. PSPA treatment also resulted in a better platform growing status, statistically higher viability, an increase in the S-phase, and more Ki67+ cells. However, neither pAkt nor pERK were detected in either group. Conclusions: We found that PSPA maintained high cell viability, boosted DNA synthesis, and preserved a high percentage of continuously cycling cells to promote cell survival and division without changing cell morphology. This paper lays the foundation for further research about the damage-protective activities of PSPA on RPE cells or human vision.

  16. Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE)

    Science.gov (United States)

    Sharon, Dror; Blackshaw, Seth; Cepko, Constance L.; Dryja, Thaddeus P.

    2002-01-01

    We used the serial analysis of gene expression (SAGE) technique to catalogue and measure the relative levels of expression of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium (RPE) from one or both of two humans, aged 88 and 44 years. The cone photoreceptor contribution to all transcription in the retina was found to be similar in the macula versus the retinal periphery, whereas the rod contribution was greater in the periphery versus the macula. Genes encoding structural proteins for axons were found to be expressed at higher levels in the macula versus the retinal periphery, probably reflecting the large proportion of ganglion cells in the central retina. In comparison with the younger eye, the peripheral retina of the older eye had a substantially higher proportion of mRNAs from genes encoding proteins involved in iron metabolism or protection against oxidative damage and a substantially lower proportion of mRNAs from genes encoding proteins involved in rod phototransduction. These differences may reflect the difference in age between the two donors or merely interindividual variation. The RPE library had numerous previously unencountered tags, suggesting that this cell type has a large, idiosyncratic repertoire of expressed genes. Comparison of these libraries with 100 reported nonocular SAGE libraries revealed 89 retina-specific or enriched genes expressed at substantial levels, of which 14 are known to cause a retinal disease and 53 are RPE-specific genes. We expect that these libraries will serve as a resource for understanding the relative expression levels of genes in the retina and the RPE and for identifying additional disease genes. PMID:11756676

  17. Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

    International Nuclear Information System (INIS)

    Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin; Yan, Biao

    2013-01-01

    Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy

  18. Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin, E-mail: jqin710@vip.sina.com; Yan, Biao, E-mail: yanbiao1982@hotmail.com

    2013-09-06

    Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy.

  19. Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Wuyang Huang

    2018-01-01

    Full Text Available Blueberries possess abundant anthocyanins, which benefit eye health. The purpose of this study was to explore the protective functional role of blueberry anthocyanin extract (BAE and its predominant constituents, malvidin (Mv, malvidin-3-glucoside (Mv-3-glc, and malvidin-3-galactoside (Mv-3-gal, on high glucose- (HG- induced injury in human retinal capillary endothelial cells (HRCECs. The results showed that BAE, Mv, Mv-3-glc, and Mv-3-gal enhanced cell viability (P<0.05 versus the HG group at 24 h; decreased the reactive oxygen species (ROS, P<0.01 versus the HG group both at 24 and 48 h; and increased the enzyme activity of catalase (CAT and superoxide dismutase (SOD (P<0.05 versus the HG group both at 24 and 48 h. Mv could greatly inhibit HG-induced Nox4 expression both at 24 and 48 h (P<0.05, while BAE and Mv-3-gal downregulated Nox4 only at 48 h (P<0.05. Mv, Mv-3-glc, and Mv-3-gal also changed nitric oxide (NO levels (P<0.05. BAE and Mv-3-glc also influenced angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF level and inhibiting Akt pathway (P<0.05. Moreover, Mv and Mv-3-glc inhibited HG-induced intercellular adhesion molecule-1 (ICAM-1, P<0.001 and nuclear factor-kappa B (NF-κB (P<0.05. It indicated that blueberry anthocyanins protected HRCECs via antioxidant and anti-inflammatory mechanisms, which could be promising molecules for the development of nutraceuticals to prevent diabetic retinopathy.

  20. HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

    Science.gov (United States)

    Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

    2014-07-01

    The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.

  1. Challenges and advantages in wide-field optical coherence tomography angiography imaging of the human retinal and choroidal vasculature at 1.7-MHz A-scan rate

    Science.gov (United States)

    Poddar, Raju; Migacz, Justin V.; Schwartz, Daniel M.; Werner, John S.; Gorczynska, Iwona

    2017-10-01

    We present noninvasive, three-dimensional, depth-resolved imaging of human retinal and choroidal blood circulation with a swept-source optical coherence tomography (OCT) system at 1065-nm center wavelength. Motion contrast OCT imaging was performed with the phase-variance OCT angiography method. A Fourier-domain mode-locked light source was used to enable an imaging rate of 1.7 MHz. We experimentally demonstrate the challenges and advantages of wide-field OCT angiography (OCTA). In the discussion, we consider acquisition time, scanning area, scanning density, and their influence on visualization of selected features of the retinal and choroidal vascular networks. The OCTA imaging was performed with a field of view of 16 deg (5 mm×5 mm) and 30 deg (9 mm×9 mm). Data were presented in en face projections generated from single volumes and in en face projection mosaics generated from up to 4 datasets. OCTA imaging at 1.7 MHz A-scan rate was compared with results obtained from a commercial OCTA instrument and with conventional ophthalmic diagnostic methods: fundus photography, fluorescein, and indocyanine green angiography. Comparison of images obtained from all methods is demonstrated using the same eye of a healthy volunteer. For example, imaging of retinal pathology is presented in three cases of advanced age-related macular degeneration.

  2. Retinal Detachment

    Directory of Open Access Journals (Sweden)

    Adnan Riaz, MD

    2018-04-01

    Full Text Available History of present illness: A 58-year-old female presented to the emergency department reporting six days of progressive, atraumatic left eye vision loss. Her symptoms started with the appearance of dark spots and “spider webs,” and then progressed to darkening of vision in her left eye. She reports mild pain since yesterday. Her review of symptoms was otherwise negative. Ocular physical examination revealed normal external appearance, intact extraocular movements, and visual acuities of 20/25 OD and light/dark sensitivity OS. Fluorescein uptake was negative and slit lamp exam was unremarkable. Significant findings: Bedside ocular ultrasound revealed a serpentine, hyperechoic membrane that appeared tethered to the optic disc posteriorly with hyperechoic material underneath. These findings are consistent with retinal detachment (RD and associated retinal hemorrhage. Discussion: The retina is a layer of organized neurons that line the posterior portion of the posterior chamber of the eye. RD occurs when this layer separates from the underlying epithelium, resulting in ischemia and progressive photoreceptor degeneration, with potentially rapid and permanent vision loss if left untreated.1 Risk factors include advanced age, male sex (60%, race (Asians and Jews, and myopia and lattice degeneration.2 Bedside ultrasound (US performed by emergency physicians provides a valuable tool that has been used by ophthalmologists for decades to evaluate intraocular disease.1,3 Findings on bedside ultrasound consistent with RD include a hyperechoic membrane floating in the posterior chamber. RD usuallyremain tethered to the optic disc posteriorly and do not cross midline, a feature distinguishing them from posterior vitreous detachments. Associated retinal hemorrhage, seen as hyperechoic material under the retinal flap, can often be seen.1,2 US can also distinguish between “mac-on” and “mac-off” detachments. If the retina is still attached to the

  3. Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

    International Nuclear Information System (INIS)

    Huang, Xionggao; Wei, Yantao; Ma, Haizhi; Zhang, Shaochong

    2012-01-01

    Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

  4. Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. Black-Right-Pointing-Pointer Rac1 is activated in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous

  5. Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats.

    Science.gov (United States)

    Wang, L; Li, P; Tian, Y; Li, Z; Lian, C; Ou, Q; Jin, C; Gao, F; Xu, J-Y; Wang, J; Wang, F; Zhang, J; Zhang, J; Li, W; Tian, H; Lu, L; Xu, G-T

    2017-01-01

    Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Retinal Pigmented Epithelial Cells Obtained from Human Induced Pluripotent Stem Cells Possess Functional Visual Cycle Enzymes in Vitro and in Vivo*

    Science.gov (United States)

    Maeda, Tadao; Lee, Mee Jee; Palczewska, Grazyna; Marsili, Stefania; Tesar, Paul J.; Palczewski, Krzysztof; Takahashi, Masayo; Maeda, Akiko

    2013-01-01

    Differentiated retinal pigmented epithelial (RPE) cells have been obtained from human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle in hiPS-RPE cells has not been adequately examined. Here we determined the expression of functional visual cycle enzymes in hiPS-RPE cells compared with that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo. hiPS-RPE cells appeared morphologically similar to mpRPE cells. Notably, expression of certain visual cycle proteins was maintained during cell culture of hiPS-RPE cells, whereas expression of these same molecules rapidly decreased in mpRPE cells. Production of the visual chromophore, 11-cis-retinal, and retinosome formation also were documented in hiPS-RPE cells in vitro. When mpRPE cells with luciferase activity were transplanted into the subretinal space of mice, bioluminance intensity was preserved for >3 months. Additionally, transplantation of mpRPE into blind Lrat−/− and Rpe65−/− mice resulted in the recovery of visual function, including increased electrographic signaling and endogenous 11-cis-retinal production. Finally, when hiPS-RPE cells were transplanted into the subretinal space of Lrat−/− and Rpe65−/− mice, their vision improved as well. Moreover, histological analyses of these eyes displayed replacement of dysfunctional RPE cells by hiPS-RPE cells. Together, our results show that hiPS-RPE cells can exhibit a functional visual cycle in vitro and in vivo. These cells could provide potential treatment options for certain blinding retinal degenerative diseases. PMID:24129572

  7. Human retinal pigment epithelial cells inhibit proliferation and IL2R expression of activated T cells

    DEFF Research Database (Denmark)

    Kaestel, Charlotte G; Jørgensen, Annette; Nielsen, Mette

    2002-01-01

    -Thymidine incorporation assay, respectively. T cells and RPE cells were cultured directly together or in a transwell system for determination of the effect of cell contact. The importance of cell surface molecules was examined by application of a panel of blocking antibodies (CD2, CD18, CD40, CD40L, CD54, CD58......) in addition to use of TCR negative T cell lines. The expression of IL2R-alpha -beta and -gamma chains of activated T cells was analysed by flow cytometry after incubation of T cells alone or with RPE cells. Human RPE cells were found to inhibit the proliferation of activated T cells by a cell contact......-beta and -gamma chain expression within 24 hr after removal from the coculture. It is concluded that the cultured human adult and foetal RPE cells inhibit the proliferation of activated T cells by a process that does not involve apoptosis. It depends on cell contact but the involved surface molecules were...

  8. Extracellular matrix components expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix.

    Science.gov (United States)

    Felemban, Majed; Dorgau, Birthe; Hunt, Nicola Claire; Hallam, Dean; Zerti, Darin; Bauer, Roman; Ding, Yuchun; Collin, Joseph; Steel, David; Krasnogor, Natalio; Al-Aama, Jumana; Lindsay, Susan; Mellough, Carla; Lako, Majlinda

    2018-05-17

    The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin and Collagen IV) were expressed in Bruch's membrane and the inner limiting membrane of the developing human retina, whilst the hyalectins (Versican and Brevican), cluster of differentiation 44 (CD44), photoreceptor-specific ECMs Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) and Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) were detected in the developing interphotoreceptor matrix (IPM). The expression of IMPG1, Versican and Brevican in the developing IPM was conserved between human developing retina and human pluripotent stem cell-derived retinal organoids. Blocking the action of CD44 and IMPG1 in pluripotent stem cell derived retinal organoids affected the development of photoreceptors, their inner/outer segments and connecting cilia and disrupted IPM formation, with IMPG1 having an earlier and more significant impact. Together, our data suggest an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation during human retinogenesis. The expression and the role of many extracellular matrix (ECM) components during human retinal development is not fully understood. In this study, expression of key ECM components (Collagen IV, Fibronectin, Brevican, Versican, IMPG1 and IMPG2) was investigated during human retinal ontogenesis. Collagen IV and Fibronectin were expressed in Bruch's membrane; whereas Brevican, Versican

  9. Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

    Science.gov (United States)

    Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

    2014-05-13

    Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  10. Retinal detachment and retinal holes in retinitis pigmentosa sine pigmento.

    Science.gov (United States)

    Csaky, K; Olk, R J; Mahl, C F; Bloom, S M

    1991-01-01

    Retinal detachment and retinal holes in two family members with retinitis pigmentosa sine pigmento are reported. We believe these are the first such cases reported in the literature. We describe the presenting symptoms and management, including cryotherapy, scleral buckling procedure, and sulfur hexafluoride injection (SF6), resulting in stable visual acuity in one case and retinal reattachment and improved visual acuity in the other case.

  11. Retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Hamel Christian

    2006-10-01

    Full Text Available Abstract Retinitis pigmentosa (RP is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms. Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema, and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis.

  12. Controlled surface morphology and hydrophilicity of polycaprolactone toward human retinal pigment epithelium cells

    International Nuclear Information System (INIS)

    Shahmoradi, Saleheh; Yazdian, Fatemeh; Tabandeh, Fatemeh; Soheili, Zahra-Soheila; Hatamian Zarami, Ashraf Sadat; Navaei-Nigjeh, Mona

    2017-01-01

    Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nanofibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12 g/mL and 20 kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120 min and 5 M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48°). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistry (ICC), MTT and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8 nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. - Highlights: • Dimethylformamide (DMF) has significant effect on reduction of fibers' diameter. • Having high hydrophilicity by alkaline hydrolysis • Suitable

  13. Controlled surface morphology and hydrophilicity of polycaprolactone toward human retinal pigment epithelium cells.

    Science.gov (United States)

    Shahmoradi, Saleheh; Yazdian, Fatemeh; Tabandeh, Fatemeh; Soheili, Zahra-Soheila; Hatamian Zarami, Ashraf Sadat; Navaei-Nigjeh, Mona

    2017-04-01

    Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nanofibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12g/mL and 20kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120min and 5M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48°). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistry (ICC), MTT and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. Copyright © 2016. Published by Elsevier B.V.

  14. Controlled surface morphology and hydrophilicity of polycaprolactone toward human retinal pigment epithelium cells

    Energy Technology Data Exchange (ETDEWEB)

    Shahmoradi, Saleheh; Yazdian, Fatemeh [Department of Life Science Engineering, Faculty of New sciences and Technologies, University of Tehran, Tehran (Iran, Islamic Republic of); Tabandeh, Fatemeh, E-mail: taban_f@nigeb.ac.ir [Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran (Iran, Islamic Republic of); Soheili, Zahra-Soheila [Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran (Iran, Islamic Republic of); Hatamian Zarami, Ashraf Sadat [Department of Life Science Engineering, Faculty of New sciences and Technologies, University of Tehran, Tehran (Iran, Islamic Republic of); Navaei-Nigjeh, Mona [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2017-04-01

    Applying scaffolds as a bed to enhance cell proliferation and even differentiation is one of the treatment of retina diseases such as age-related macular degeneration (AMD) which deteriorating photoreceptors and finally happening blindness. In this study, aligned polycaprolactone (PCL) nanofibers were electrospun and at different conditions and their characteristics were measured by scanning electron microscope (SEM) and contact angle. Response surface methodology (RSM) was used to optimize the diameter of fabricated nanofibers. Two factors as solution concentration and voltage value were considered as independent variables and their effects on nanofibers' diameters were evaluated by central composite design and the optimum conditions were obtained as 0.12 g/mL and 20 kV, respectively. In order to decrease the hydrophobicity of PCL, the surface of the fabricated scaffolds was modified by alkaline hydrolysis method. Contact time of the scaffolds and alkaline solution and concentration of alkaline solution were optimized using Box Behnken design and (120 min and 5 M were the optimal, respectively). Contact angle measurement showed the high hydrophilicity of treated scaffolds (with contact angle 7.48°). Plasma surface treatment was applied to compare the effect of using two kinds of surface modification methods simultaneously on hydrolyzed scaffolds. The RPE cells grown on scaffolds were examined by immunocytochemistry (ICC), MTT and continuous inspection of cellular morphology. Interestingly, Human RPE cells revealed their characteristic morphology on hydrolyzed scaffold well. As a result, we introduced a culture substrate with low diameter (185.8 nm), high porosity (82%) and suitable hydrophilicity (with contact angle 7.48 degree) which can be promising for hRPE cell transplantation. - Highlights: • Dimethylformamide (DMF) has significant effect on reduction of fibers' diameter. • Having high hydrophilicity by alkaline hydrolysis • Suitable

  15. Disease susceptibility of the human macula: differential gene transcription in the retinal pigmented epithelium/choroid.

    Science.gov (United States)

    Radeke, Monte J; Peterson, Katie E; Johnson, Lincoln V; Anderson, Don H

    2007-09-01

    The discoveries of gene variants associated with macular diseases have provided valuable insight into their molecular mechanisms, but they have not clarified why the macula is particularly vulnerable to degenerative disease. Its predisposition may be attributable to specialized structural features and/or functional properties of the underlying macular RPE/choroid. To examine the molecular basis for the macula's disease susceptibility, we compared the gene expression profile of the human RPE/choroid in the macula with the profile in the extramacular region using DNA microarrays. Seventy-five candidate genes with differences in macular:extramacular expression levels were identified by microarray analysis, of which 29 were selected for further analysis. Quantitative PCR confirmed that 21 showed statistically significant differences in expression. Five genes were expressed at higher levels in the macula. Two showed significant changes in the macular:extramacular expression ratio; another two exhibited changes in absolute expression level, as a function of age or AMD. Several of the differentially expressed genes have potential relevance to AMD pathobiology. One is an RPE cell growth factor (TFPI2), five are extracellular matrix components (DCN, MYOC, OGN, SMOC2, TFPI2), and six are related to inflammation (CCL19, CCL26, CXCL14, SLIT2) and/or angiogenesis (CXCL14, SLIT2, TFPI2, WFDC1). The identification of regional differences in gene expression in the RPE/choroid is a first step in clarifying the macula's propensity for degeneration. These findings lay the groundwork for further studies into the roles of the corresponding gene products in the normal, aged, and diseased macula.

  16. Modelling the optical response of human retinal photoreceptors to plane wave illumination with the finite integration technique

    Science.gov (United States)

    Akhlagh Moayed, Alireza; Dang, Shannon; Ramahi, Omar M.; Bizheva, Kostadinka K.

    2009-02-01

    The early stages of ocular diseases such as Diabetic Retinopathy are manifested by morphological changes in retinal tissue occurring on cellular level. Therefore, a number of ophthalmic diseases can be diagnosed at an early stage by detecting spatial and temporal variations in the scattering profile of retinal tissue. It was recently demonstrated that, OCT can be used to probe the functional response of retinal photoreceptors to external light stimulation [1]-[3]. fUHROCT measures localized differential changes in the retina reflectivity over time resulting from external light stimulation of the retina. Currently the origins of the observed reflectivity changes are not well understood. However, due to the complex nature of retinal physiology using purely experimental approaches in this case is problematic. For example fUHROCT is sensitive to small changes in the refractive index of biological tissue which as demonstrated previously, can result from a number of processes such as membrane hyperpolarization, osmotic swelling, metabolic changes, etc. In this paper, we present a computational model of interaction between photoreceptor cells and optical plane wave based on the Finite Integration Technique (FIT).

  17. Advances in Retinal Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2013-01-01

    Full Text Available Tremendous progress has been made in recent years to generate retinal cells from pluripotent cell sources. These advances provide hope for those suffering from blindness due to lost retinal cells. Understanding the intrinsic genetic network in model organisms, like fly and frog, has led to a better understanding of the extrinsic signaling pathways necessary for retinal progenitor cell formation in mouse and human cell cultures. This review focuses on the culture methods used by different groups, which has culminated in the generation of laminated retinal tissue from both embryonic and induced pluripotent cells. The review also briefly describes advances made in transplantation studies using donor retinal progenitor and cultured retinal cells.

  18. Human Adipose-Derived Stem Cells Delay Retinal Degeneration in Royal College of Surgeons Rats Through Anti-Apoptotic and VEGF-Mediated Neuroprotective Effects.

    Science.gov (United States)

    Li, Z; Wang, J; Gao, F; Zhang, J; Tian, H; Shi, X; Lian, C; Sun, Y; Li, W; Xu, J-Y; Li, P; Zhang, J; Gao, Z; Xu, J; Wang, F; Lu, L; Xu, G-T

    2016-01-01

    Stem cell therapy is a promising therapeutic approach for retinal degeneration (RD). Our study investigated the effects of human adipose derived stem cell (hADSCs) on Royal College of Surgeons (RCS) rats. Green fluorescent protein (GFP)-labeled hADSCs were transplanted subretinally into RCS rats at postnatal (PN) 21 days to explore potential therapeutic effects, while adeno-associated viral vector (AAV2)-vascular endothelial growth factor (VEGF) and siVEGF-hADSCs were used to aid the mechanistic dissections. Visual function was evaluated by Electroretinogram (ERG) recording. Potential transdifferentiations were examined by Immunofluorescence (IF) and gene expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Apoptotic retinal cells were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and the cytokines secreted by hADSCs were measured by Enzyme-linked Immunosorbent Assay (ELISA). The visual function of RCS rats began to decrease one week after their eyes opened at PN week 3 and almost lost in PN 5 weeks, accompanied by the loss of retinal outer nuclear layer (ONL). Subretinal transplantation of hADSCs significantly improved the visual function 2 weeks after the transplantation and such therapeutic effect persisted up to 8 weeks after the treatment (PN 11 weeks), with 3-4 rows of photoreceptors remained in the ONL and reduced apoptosis. Consistent with these phenotypic changes, the gene expression of rod photoreceptor markers Rhodopsin (Rho), Crx and Opsin (Opn1) in RCS rats showed obvious decreasing trends over time after PN 3 weeks, but were elevated with hADSC treatment. hADSC transplantation also repressed the expressions of Bax, Bak and Caspase 3, but not the expression of anti-apoptotic genes, including Bcl-2 and Bcl-XL. Finally, substantial VEGF, hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF) secretions from hADSCs were detected, while endogenous

  19. Kaempferol targets estrogen-related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions.

    Science.gov (United States)

    Wu, Yan; Zhang, Qinmei; Zhang, Rui

    2017-12-01

    Diabetic retinopathy (DR) is the most common complication of diabetes and a major cause of new-onset blindness in the developed world. The present study aimed to examine the effect of kaempferol on high glucose-induced human retinal endothelial cells (HRECs) in vitro . The expression levels of various mRNAs and proteins were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The target of kaempferol was determined using a luciferase reporter assay. In addition, HREC proliferation, migration and cell sprouting were determined using Cell Counting kit-8, wound scratch and tube formation assays, respectively. RT-qPCR and western blotting results showed that treatment with 30 mM glucose for 12, 24 and 48 h increased the expression level of estrogen-related receptor α (ERRα) mRNA and protein. The luciferase reporter assay demonstrated that kaempferol inhibited ERRα activity in HRECs. Compared with 5 mM normal glucose treatment, high (30 mM) glucose significantly promoted the proliferation, migration and tube formation of HRECs, which was antagonized by 10 and 30 µM kaempferol in a dose-dependent manner. Treatment with 30 mM glucose also increased the expression of vascular endothelial growth factor (VEGF) mRNA and protein, and the expression levels of VEGF mRNA and protein were suppressed by kaempferol (10 and 30 µM). Kaempferol (30 µM) treatment also increased the expression levels of thrombospondin 1 (TSP-1) and a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS-1) mRNA; however, TSP-1 and ADAMTS-1 levels did not differ between high glucose and normal (5 mM) glucose conditions. The results of this study suggest that kaempferol targets ERRα and suppresses the angiogenesis of HRECs under high glucose conditions. Kaempferol may be a potential drug for use in controlling the progression of DR; however, in vivo studies are required to evaluate its efficacy and safety.

  20. A Computational Approach From Gene to Structure Analysis of the Human ABCA4 Transporter Involved in Genetic Retinal Diseases.

    Science.gov (United States)

    Trezza, Alfonso; Bernini, Andrea; Langella, Andrea; Ascher, David B; Pires, Douglas E V; Sodi, Andrea; Passerini, Ilaria; Pelo, Elisabetta; Rizzo, Stanislao; Niccolai, Neri; Spiga, Ottavia

    2017-10-01

    The aim of this article is to report the investigation of the structural features of ABCA4, a protein associated with a genetic retinal disease. A new database collecting knowledge of ABCA4 structure may facilitate predictions about the possible functional consequences of gene mutations observed in clinical practice. In order to correlate structural and functional effects of the observed mutations, the structure of mouse P-glycoprotein was used as a template for homology modeling. The obtained structural information and genetic data are the basis of our relational database (ABCA4Database). Sequence variability among all ABCA4-deposited entries was calculated and reported as Shannon entropy score at the residue level. The three-dimensional model of ABCA4 structure was used to locate the spatial distribution of the observed variable regions. Our predictions from structural in silico tools were able to accurately link the functional effects of mutations to phenotype. The development of the ABCA4Database gathers all the available genetic and structural information, yielding a global view of the molecular basis of some retinal diseases. ABCA4 modeled structure provides a molecular basis on which to analyze protein sequence mutations related to genetic retinal disease in order to predict the risk of retinal disease across all possible ABCA4 mutations. Additionally, our ABCA4 predicted structure is a good starting point for the creation of a new data analysis model, appropriate for precision medicine, in order to develop a deeper knowledge network of the disease and to improve the management of patients.

  1. Decreased VEGF-A and sustained PEDF expression in a human retinal pigment epithelium cell line cultured under hypothermia

    Directory of Open Access Journals (Sweden)

    Masayuki Takeyama

    2015-01-01

    Full Text Available BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A and in vitro angiogen-esis in retinal pigment epithelium (RPE. RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31°C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF. We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.

  2. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE.

    Science.gov (United States)

    Giurdanella, Giovanni; Lazzara, Francesca; Caporarello, Nunzia; Lupo, Gabriella; Anfuso, Carmelina Daniela; Eandi, Chiara M; Leggio, Gian Marco; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

    2017-10-15

    Diabetic retinopathy is characterized by the breakdown of endothelial blood-retinal barrier. We tested the hypothesis that sulodexide (SDX), a highly purified glycosaminoglycan composed of 80% iduronylglycosaminoglycan sulfate and 20% dermatan sulfate, protects human retinal endothelial cells (HREC) from high glucose (HG)-induced damage, through the suppression of inflammatory ERK/cPLA2/COX-2/PGE 2 pathway, by blocking the effect of advanced glycation end-products (AGEs). HREC were treated with HG (25mM) or AGEs (glycated-BSA, 2mg/ml) for 48h, with or without SDX (60μg/ml) or aflibercept (AFL, 40μg/ml), a VEGF-trap. SDX protected HREC from HG-induced damage (MTT and LDH release) and preserved their blood-retinal barrier-like properties (Trans Endothelial Electrical Resistance and junction proteins, claudin-5, VE-cadherin and occludin, immunofluorescence and immunoblot) as well as their angiogenic potential (Tube Formation Assay). Both HG and AGEs increased phosphoERK and phospho-cPLA 2 , an effect counteracted by SDX and, less efficiently, by AFL. Both HG and exogenous VEGF (80ng/ml) increased PGE 2 release, an effect partially reverted by SDX for HG and by AFL for VEGF. Analysis of NFκB activity revealed that HG increased the abundance of p65 in the nuclear fraction (nuclear translocation), an effect entirely reverted by SDX, but only partially by AFL. SDX, AFL and SDX+AFL protected HREC even when added 24h after HG. These data show that SDX protects HREC from HG damage and suggest that it counteracts the activation of ERK/cPLA2/COX-2/PGE 2 pathway by reducing AGE-related signaling and downstream NFκB activity. This mechanism, partially distinct from VEGF blockade, may contribute to the therapeutic effect of SDX. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Everyday imagery

    DEFF Research Database (Denmark)

    Peters, Chris; Allan, Stuart

    2016-01-01

    the gradual disappearance of media from personal consciousness in a digital age. If ceaselessness is a defining characteristic of the current era, our analysis reveals that the use of smartphone cameras is indicative of people affectively and self-consciously deploying the technology to try to arrest......User-based research into the lived experiences associated with smartphone camera practices – in particular, the taking, storing, curating, and sharing of personal imagery in the digital media sphere – remains scarce, especially in contrast to their increasing ubiquity. Accordingly, this article...... social bonds, and encompass a future-oriented perspective. Relatedly, in terms of photographic composition, visual content tends to circulate around the social presence of others, boundedness of event, perceived aesthetic value, and intended shareability. Our findings question certain formulations about...

  4. Taurine uptake by human retinal pigment epithelium: implications for the transport of small solutes between the choroid and the outer retina.

    Science.gov (United States)

    Hillenkamp, Jost; Hussain, Ali A; Jackson, Timothy L; Cunningham, Joanna R; Marshall, John

    2004-12-01

    To characterize the Michaelis-Menten kinetics of the taurine transporter (TT) in retinal pigment epithelium (RPE) freshly isolated from human donor eyes. To identify the rate limiting compartment in the pathway of taurine delivery from the choroidal blood supply to the outer retina composed by Bruch's-choroid (BC) and the RPE in the human older age group. In human donor samples (4 melanoma-affected eyes, and 14 control eyes; age range, 62-93 years), radiochemical techniques were used to determine the RPE taurine accumulation at various exogenous concentrations. The transport capability of human RPE was obtained from a kinetic analysis of the high-affinity carrier over a substrate concentration of 1 to 60 microM taurine. Uptake of taurine into human RPE at a taurine concentration of 1 microM was independent of donor age (P > 0.05) and averaged at 2.83 +/- 0.27 (SEM) pmol/10 minutes per 6-mm trephine. Taurine transport by human RPE was mediated by a high-affinity carrier of K(m) 50 microM and V(max) of 267 pmol/10 minutes per 5-mm disc. In human donor RPE, uptake of taurine remained viable in the age range 62 to 93 years. Taurine transport rates in the RPE were lower than across the isolated BC complex, and thus the data suggest that the former compartment houses the rate-limiting step in the delivery of taurine to the outer retina.

  5. Missed retinal breaks in rhegmatogenous retinal detachment

    Directory of Open Access Journals (Sweden)

    Brijesh Takkar

    2016-12-01

    Full Text Available AIM: To evaluate the causes and associations of missed retinal breaks (MRBs and posterior vitreous detachment (PVD in patients with rhegmatogenous retinal detachment (RRD. METHODS: Case sheets of patients undergoing vitreo retinal surgery for RRD at a tertiary eye care centre were evaluated retrospectively. Out of the 378 records screened, 253 were included for analysis of MRBs and 191 patients were included for analysis of PVD, depending on the inclusion criteria. Features of RRD and retinal breaks noted on examination were compared to the status of MRBs and PVD detected during surgery for possible associations. RESULTS: Overall, 27% patients had MRBs. Retinal holes were commonly missed in patients with lattice degeneration while missed retinal tears were associated with presence of complete PVD. Patients operated for cataract surgery were significantly associated with MRBs (P=0.033 with the odds of missing a retinal break being 1.91 as compared to patients with natural lens. Advanced proliferative vitreo retinopathy (PVR and retinal bullae were the most common reasons for missing a retinal break during examination. PVD was present in 52% of the cases and was wrongly assessed in 16%. Retinal bullae, pseudophakia/aphakia, myopia, and horse shoe retinal tears were strongly associated with presence of PVD. Traumatic RRDs were rarely associated with PVD. CONCLUSION: Pseudophakic patients, and patients with retinal bullae or advanced PVR should be carefully screened for MRBs. Though Weiss ring is a good indicator of PVD, it may still be over diagnosed in some cases. PVD is associated with retinal bullae and pseudophakia, and inversely with traumatic RRD.

  6. Implementations of three OCT angiography (OCTA) methods with 1.7 MHz A-scan rate OCT system on imaging of human retinal and choroidal vasculature

    Science.gov (United States)

    Poddar, Raju; Werner, John S.

    2018-06-01

    We present noninvasive depth-resolved imaging of human retinal and choroidal microcirculation with an ultrahigh-speed (1.7 MHz A-scans/s), Fourier-domain mode locked (FDML) swept-source optical coherence tomography (SS-OCT) system having a central wavelength of 1065 nm. Three OCT angiography (OCTA) motion based contrast methods, namely phase variance (PV), amplitude decorrelation (AD) and Joint Spectral and Time domain OCT (STdOCT) were implemented. The OCTA imaging was performed with a field of view of 16° (5 mm × 5 mm) and 30° (9 mm × 9 mm), on the retina. A qualitative comparison of images obtained with all three OCTA methods is demonstrated using the same eye of a healthy volunteer. Different parameters, namely acquisition time, scanning area, and scanning density, are discussed. The phase-variance OCTA (PV-OCTA) method produced relatively better results than the other two. Different features regarding the retinal and choroidal vessels are described in different subjects.

  7. Influence of transverse mode on retinal spot size and retinal injury effect: A theoretical analysis on 532-nm laser

    Directory of Open Access Journals (Sweden)

    Jia-Rui Wang

    2014-05-01

    Full Text Available The fundamental transverse mode (TEM00 is preferable for experimental and theoretical study on the laser-induced retinal injury effect, for it can produce the minimal retinal image and establish the most strict laser safety standards. But actually lasers with higher order mode were frequently used in both earlier and recent studies. Generally higher order mode leads to larger retinal spot size and so higher damage threshold, but there are few quantitative analyses on this problem. In this paper, a four-surface schematic eye model is established for human and macaque. The propagation of 532-nm laser in schematic eye is analyzed by the ABCD law of Gaussian optics. It is shown that retinal spot size increases with laser transverse mode order. For relative lower mode order, the retinal spot diameter will not exceed the minimum laser-induced retinal lesion (25 ~ 30 μm in diameter, and so has little effect on retinal damage threshold. While for higher order mode, the larger retinal spot requires more energy to induce injury and so the damage threshold increases. When beam divergence is lowered, the retinal spot size decreases correspondingly, so the effect of mode order can be compensated. The retinal spot size of macaque is slightly smaller than that of human and the ratio between them is independent of mode order. We conclude that the laser mode order has significant influence on retinal spot size but limited influence on the retinal injury effect.

  8. A mathematical model for describing the retinal nerve fiber bundle trajectories in the human eye : Average course, variability, and influence of refraction, optic disc size and optic disc position

    NARCIS (Netherlands)

    Jansonius, Nomdo M.; Schiefer, Julia; Nevalainen, Jukka; Paetzold, Jens; Schiefer, Ulrich

    2012-01-01

    Previously we developed a mathematical model for describing the retinal nerve fiber bundle trajectories in the superior-temporal and inferior-temporal regions of the human retina, based on traced trajectories extracted from fundus photographs. Aims of the current study were to (i) validate the

  9. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  10. Cadherins in the retinal pigment epithelium (RPE revisited: P-cadherin is the highly dominant cadherin expressed in human and mouse RPE in vivo.

    Directory of Open Access Journals (Sweden)

    Xue Yang

    Full Text Available The retinal pigment epithelium (RPE supports the health and function of retinal photoreceptors and is essential for normal vision. RPE cells are post-mitotic, terminally differentiated, and polarized epithelial cells. In pathological conditions, however, they lose their epithelial integrity, become dysfunctional, even dedifferentiate, and ultimately die. The integrity of epithelial cells is maintained, in part, by adherens junctions, which are composed of cadherin homodimers and p120-, β-, and α-catenins linking to actin filaments. While E-cadherin is the major cadherin for forming the epithelial phenotype in most epithelial cell types, it has been reported that cadherin expression in RPE cells is different from other epithelial cells based on results with cultured RPE cells. In this study, we revisited the expression of cadherins in the RPE to clarify their relative contribution by measuring the absolute quantity of cDNAs produced from mRNAs of three classical cadherins (E-, N-, and P-cadherins in the RPE in vivo. We found that P-cadherin (CDH3 is highly dominant in both mouse and human RPE in situ. The degree of dominance of P-cadherin is surprisingly large, with mouse Cdh3 and human CDH3 accounting for 82-85% and 92-93% of the total of the three cadherin mRNAs, respectively. We confirmed the expression of P-cadherin protein at the cell-cell border of mouse RPE in situ by immunofluorescence. Furthermore, we found that oxidative stress induces dissociation of P-cadherin and β-catenin from the cell membrane and subsequent translocation of β-catenin into the nucleus, resulting in activation of the canonical Wnt/β-catenin pathway. This is the first report of absolute comparison of the expression of three cadherins in the RPE, and the results suggest that the physiological role of P-cadherin in the RPE needs to be reevaluated.

  11. Gene expression changes in the retina following subretinal injection of human neural progenitor cells into a rodent model for retinal degeneration.

    Science.gov (United States)

    Jones, Melissa K; Lu, Bin; Saghizadeh, Mehrnoosh; Wang, Shaomei

    2016-01-01

    Retinal degenerative diseases (RDDs) affect millions of people and are the leading cause of vision loss. Although treatment options for RDDs are limited, stem and progenitor cell-based therapies have great potential to halt or slow the progression of vision loss. Our previous studies have shown that a single subretinal injection of human forebrain derived neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) retinal degenerate rat offers long-term preservation of photoreceptors and visual function. Furthermore, neural progenitor cells are currently in clinical trials for treating age-related macular degeneration; however, the molecular mechanisms of stem cell-based therapies are largely unknown. This is the first study to analyze gene expression changes in the retina of RCS rats following subretinal injection of hNPCs using high-throughput sequencing. RNA-seq data of retinas from RCS rats injected with hNPCs (RCS(hNPCs)) were compared to sham surgery in RCS (RCS(sham)) and wild-type Long Evans (LE(sham)) rats. Differential gene expression patterns were determined with in silico analysis and confirmed with qRT-PCR. Function, biologic, cellular component, and pathway analyses were performed on differentially expressed genes and investigated with immunofluorescent staining experiments. Analysis of the gene expression data sets identified 1,215 genes that were differentially expressed between RCS(sham) and LE(sham) samples. Additionally, 283 genes were differentially expressed between the RCS(hNPCs) and RCS(sham) samples. Comparison of these two gene sets identified 68 genes with inverse expression (termed rescue genes), including Pdc, Rp1, and Cdc42ep5. Functional, biologic, and cellular component analyses indicate that the immune response is enhanced in RCS(sham). Pathway analysis of the differential expression gene sets identified three affected pathways in RCS(hNPCs), which all play roles in phagocytosis signaling. Immunofluorescent staining

  12. NAIP 2015 Imagery Feedback

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — The NAIP 2015 Imagery Feedback web application allows users to make comments and observations about the quality of the 2015 National Agriculture Imagery Program...

  13. Current Resource Imagery Projects

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — Map showing coverage of current Resource imagery projects. High resolution/large scale Resource imagery is typically acquired for the U.S. Forest Service and other...

  14. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

    Science.gov (United States)

    Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

    2014-01-01

    Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

  15. Resveratrol Protects Against Ultraviolet A-Mediated Inhibition of the Phagocytic Function of Human Retinal Pigment Epithelial Cells Via Large-Conductance Calcium-Activated Potassium Channels

    Directory of Open Access Journals (Sweden)

    Shwu-Jiuan Sheu

    2009-07-01

    Full Text Available This study was undertaken to examine the protective effect of resveratrol on human retinal pigment epithelial (RPE cell phagocytosis against ultraviolet irradiation damage. Cultured RPE cells were exposed to ultraviolet A (UVA, 20 minutes irradiation, and treated with meclofenamic acid (30μM, 20 minutes, paxilline (100 μM, 20 minutes or resveratrol (10μM, 20 minutes. Meclofenamic acid and resveratrol were given after exposure to UVA. Pretreatment with meclofenamic acid, resveratrol or paxilline before UVA irradiation was also performed. Fluorescent latex beads were then fed for 4 hours and the phagocytotic function was assessed by flow cytometry. UVA irradiation inhibited the phagocytic function of human RPE cells. The large-conductance calcium-activated potassium channel activator meclofenamic acid ameliorated the damage caused by UVA irradiation. Pretreatment with resveratrol acid also provided protection against damage caused by UVA. Posttreatment with meclofenamic acid offered mild protection, whereas resveratrol did not. In conclusion, the red wine flavonoid resveratrol ameliorated UVA-mediated inhibition of human RPE phagocytosis. The underlying mechanism might involve the large-conductance calcium-activated potassium channels.

  16. 7,8-Dihydroxyflavone ameliorates high-glucose induced diabetic apoptosis in human retinal pigment epithelial cells by activating TrkB.

    Science.gov (United States)

    Yu, Xiaoyi; Liu, Qiuhong; Wang, Xiaochuan; Liu, Hong; Wang, Yan

    2018-01-01

    In diabetic retinopathy, prolonged high-level blood glucose induced significant impairments among various retinal tissues, including retinal pigment epithelial (RPE) cells. In an in vitro model of human RPE cells, we evaluated whether 7,8-Dihydroxyflavone (DHF) may effectively prevent high glucose-induced diabetic apoptosis among human RPE cells. ARPE-19 cells, a Human RPE cell line, were treated with d-glucose (50 mM) to induce apoptosis in vitro. Prior to glucose, ARPE-19 cells were pre-incubated with various concentrations of DHF. The effect of DHF on d-glucose-induced apoptosis was examined by TUNEL assay, in a concentration-dependent manner. The biological effects of DHF on Caspase-9 (Casp-9) and TrkB signaling pathways in d-glucose-injured ARPE-19 cells were evaluated by qRT-PCR and western blot (WB) assays. A TrkB antagonist, K252a, was also applied in DHF and d-glucose treated ARPE-19 cells. Possible effect of K252a blocking TrkB signaling pathway, thus reversing DHF-modulated apoptosis prevention was also examined by TUNEL and WB assays. DHF ameliorated d-glucose-induced diabetic apoptosis in ARPE-19 cells. Apoptotic factor Casp-9, at both mRNA and protein levels, were drastically inhibited by DHF in d-glucose-injured ARPE-19 cells. Also, DHF activated TrkB signaling pathway through phosphorylation. K252a dramatically reversed the preventive effect of DHF on d-glucose-induced apoptosis in ARPE-19 cells. Further investigation showed that K252a functioned through de-activating or de-phosphorylating TrkB signaling pathway. This work demonstrates that DHF, through activation of TrkB signaling pathway, has a preventive function in d-glucose-induced apoptosis in PRE cells in diabetic retinopathy. Copyright © 2017. Published by Elsevier Inc.

  17. The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

    Directory of Open Access Journals (Sweden)

    Richard J. Davis

    2017-07-01

    Full Text Available Age-related macular degeneration (AMD is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC-derived RPE cells (RPESC-RPE preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.

  18. Normalization of satellite imagery

    Science.gov (United States)

    Kim, Hongsuk H.; Elman, Gregory C.

    1990-01-01

    Sets of Thematic Mapper (TM) imagery taken over the Washington, DC metropolitan area during the months of November, March and May were converted into a form of ground reflectance imagery. This conversion was accomplished by adjusting the incident sunlight and view angles and by applying a pixel-by-pixel correction for atmospheric effects. Seasonal color changes of the area can be better observed when such normalization is applied to space imagery taken in time series. In normalized imagery, the grey scale depicts variations in surface reflectance and tonal signature of multi-band color imagery can be directly interpreted for quantitative information of the target.

  19. Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model

    Directory of Open Access Journals (Sweden)

    Alvaro Plaza Reyes

    2016-01-01

    Full Text Available Human embryonic stem cell (hESC-derived retinal pigment epithelial (RPE cells could replace lost tissue in geographic atrophy (GA but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model.

  20. Focal retinal phlebitis.

    Science.gov (United States)

    Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

    2012-01-01

    To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

  1. Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device.

    Science.gov (United States)

    Hahn, Paul; Migacz, Justin; O'Donnell, Rachelle; Day, Shelley; Lee, Annie; Lin, Phoebe; Vann, Robin; Kuo, Anthony; Fekrat, Sharon; Mruthyunjaya, Prithvi; Postel, Eric A; Izatt, Joseph A; Toth, Cynthia A

    2013-01-01

    and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.

  2. Stereoscopy in cinematographic synthetic imagery

    Science.gov (United States)

    Eisenmann, Jonathan; Parent, Rick

    2009-02-01

    In this paper we present experiments and results pertaining to the perception of depth in stereoscopic viewing of synthetic imagery. In computer animation, typical synthetic imagery is highly textured and uses stylized illumination of abstracted material models by abstracted light source models. While there have been numerous studies concerning stereoscopic capabilities, conventions for staging and cinematography in stereoscopic movies have not yet been well-established. Our long-term goal is to measure the effectiveness of various cinematography techniques on the human visual system in a theatrical viewing environment. We would like to identify the elements of stereoscopic cinema that are important in terms of enhancing the viewer's understanding of a scene as well as providing guidelines for the cinematographer relating to storytelling. In these experiments we isolated stereoscopic effects by eliminating as many other visual cues as is reasonable. In particular, we aim to empirically determine what types of movement in synthetic imagery affect the perceptual depth sensing capabilities of our viewers. Using synthetic imagery, we created several viewing scenarios in which the viewer is asked to locate a target object's depth in a simple environment. The scenarios were specifically designed to compare the effectiveness of stereo viewing, camera movement, and object motion in aiding depth perception. Data were collected showing the error between the choice of the user and the actual depth value, and patterns were identified that relate the test variables to the viewer's perceptual depth accuracy in our theatrical viewing environment.

  3. Retinal detachment following endophthalmitis.

    Science.gov (United States)

    Nelsen, P T; Marcus, D A; Bovino, J A

    1985-08-01

    Fifty-five consecutive patients with a clinical diagnosis of bacterial endophthalmitis were reviewed. All patients were treated with systemic, periocular, topical, and intravitreal antibiotics. In addition, 33 of the patients underwent a pars plana vitrectomy. Nine retinal detachments occurred within six months of initial diagnosis. The higher frequency of retinal detachment in the vitrectomy group (21%) as compared to those patients managed without vitrectomy (9%) may be explained by a combination of surgical complications and the increased severity of endophthalmitis in the vitrectomy group. The two patients who developed retinal detachment during vitrectomy surgery rapidly progressed to no light perception. Conversely, the repair of retinal detachments diagnosed postoperatively had a good prognosis.

  4. Identifying Spatial Units of Human Occupation in the Brazilian Amazon Using Landsat and CBERS Multi-Resolution Imagery

    OpenAIRE

    Dal’Asta, Ana Paula; Brigatti, Newton; Amaral, Silvana; Escada, Maria Isabel Sobral; Monteiro, Antonio Miguel Vieira

    2012-01-01

    Every spatial unit of human occupation is part of a network structuring an extensive process of urbanization in the Amazon territory. Multi-resolution remote sensing data were used to identify and map human presence and activities in the Sustainable Forest District of Cuiabá-Santarém highway (BR-163), west of Pará, Brazil. The limits of spatial units of human occupation were mapped based on digital classification of Landsat-TM5 (Thematic Mapper 5) image (30m spatial resolution). High-spatial-...

  5. Structure and barrier properties of human embryonic stem cell-derived retinal pigment epithelial cells are affected by extracellular matrix protein coating.

    Science.gov (United States)

    Sorkio, Anni; Hongisto, Heidi; Kaarniranta, Kai; Uusitalo, Hannu; Juuti-Uusitalo, Kati; Skottman, Heli

    2014-02-01

    Extracellular matrix (ECM) interactions play a vital role in cell morphology, migration, proliferation, and differentiation of cells. We investigated the role of ECM proteins on the structure and function of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells during their differentiation and maturation from hESCs into RPE cells in adherent differentiation cultures on several human ECM proteins found in native human Bruch's membrane, namely, collagen I, collagen IV, laminin, fibronectin, and vitronectin, as well as on commercial substrates of xeno-free CELLstart™ and Matrigel™. Cell pigmentation, expression of RPE-specific proteins, fine structure, as well as the production of basal lamina by hESC-RPE on different protein coatings were evaluated after 140 days of differentiation. The integrity of hESC-RPE epithelium and barrier properties on different coatings were investigated by measuring transepithelial resistance. All coatings supported the differentiation of hESC-RPE cells as demonstrated by early onset of cell pigmentation and further maturation to RPE monolayers after enrichment. Mature RPE phenotype was verified by RPE-specific gene and protein expression, correct epithelial polarization, and phagocytic activity. Significant differences were found in the degree of RPE cell pigmentation and tightness of epithelial barrier between different coatings. Further, the thickness of self-assembled basal lamina and secretion of the key ECM proteins found in the basement membrane of the native RPE varied between hESC-RPE cultured on compared protein coatings. In conclusion, this study shows that the cell culture substrate has a major effect on the structure and basal lamina production during the differentiation and maturation of hESC-RPE potentially influencing the success of cell integrations and survival after cell transplantation.

  6. Mouse Retinal Pigmented Epithelial Cell Lines retain their phenotypic characteristics after transfection with Human Papilloma Virus: A new tool to further the study of RPE biology

    Science.gov (United States)

    Catanuto, Paola; Espinosa-Heidmann, Diego; Pereira-Simon, Simone; Sanchez, Patricia; Salas, Pedro; Hernandez, Eleut; Cousins, Scott W.; Elliot, Sharon J.

    2009-01-01

    Development of immortalized mouse retinal pigmented epithelial cell (RPE) lines that retain many of their in vivo phenotypic characteristics, would aid in studies of ocular diseases including age related macular degeneration (AMD). RPE cells were isolated from 16 month old (estrogen receptor knockout) ERKOα and ERKOβ mice and their C57Bl/6 wild type littermates. RPE65 and cellular retinaldehyde binding protein (CRALBP) expression, in vivo markers of RPE cells, were detected by real-time RT-PCR and western analysis. We confirmed the presence of epithelial cell markers, ZO1, cytokeratin 8 and 18 by immunofluorescence staining. In addition, we confirmed the distribution of actin filaments and the expression of ezrin. To develop cell lines, RPE cells were isolated, propagated and immortalized using human papilloma virus (HPV) 16 (E6/E7). RPE-specific markers and morphology were assessed before and after immortalization. In wildtype littermate controls, there was no evidence of any alterations in the parameters that we examined including MMP-2, TIMP-2, collagen type IV, and estrogen receptor (ER) α and ERβ protein expression and ER copy number ratio. Therefore, immortalized mouse RPE cell lines that retain their in vivo phenotype can be isolated from either pharmacologically or genetically manipulated mice, and may be used to study RPE cell biology. PMID:19013153

  7. Stem cells in retinal regeneration: past, present and future.

    Science.gov (United States)

    Ramsden, Conor M; Powner, Michael B; Carr, Amanda-Jayne F; Smart, Matthew J K; da Cruz, Lyndon; Coffey, Peter J

    2013-06-01

    Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

  8. Automatic segmentation of blood vessels from retinal fundus images ...

    Indian Academy of Sciences (India)

    The retinal blood vessels were segmented through color space conversion and color channel .... Retinal blood vessel segmentation was also attempted through multi-scale operators. A few works in this ... fundus camera at 35 degrees field of view. The image ... vessel segmentation is available from two human observers.

  9. Retinitis-pigmentosa-like tapetoretinal degeneration in a rabbit breed.

    Science.gov (United States)

    Reichenbach, A; Baar, U

    1985-08-15

    By chance, we found a rabbit strain with retinal dystrophy. The eyes of these rabbits were examined by ophthalmoscopy, electroretinography, histology, and cytology--the latter after retina dissociation with papaine. The results suggest this rabbit strain to be a possible animal model for human retinitis pigmentosa.

  10. Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells.

    Directory of Open Access Journals (Sweden)

    Takuya Kuroda

    Full Text Available Human induced pluripotent stem cells (hiPSCs possess the capabilities of self-renewal and differentiation into multiple cell types, and they are free of the ethical problems associated with human embryonic stem cells (hESCs. These characteristics make hiPSCs a promising choice for future regenerative medicine research. There are significant obstacles, however, preventing the clinical use of hiPSCs. One of the most obvious safety issues is the presence of residual undifferentiated cells that have tumorigenic potential. To locate residual undifferentiated cells, in vivo teratoma formation assays have been performed with immunodeficient animals, which is both costly and time-consuming. Here, we examined three in vitro assay methods to detect undifferentiated cells (designated an in vitro tumorigenicity assay: soft agar colony formation assay, flow cytometry assay and quantitative real-time polymerase chain reaction assay (qRT-PCR. Although the soft agar colony formation assay was unable to detect hiPSCs even in the presence of a ROCK inhibitor that permits survival of dissociated hiPSCs/hESCs, the flow cytometry assay using anti-TRA-1-60 antibody detected 0.1% undifferentiated hiPSCs that were spiked in primary retinal pigment epithelial (RPE cells. Moreover, qRT-PCR with a specific probe and primers was found to detect a trace amount of Lin28 mRNA, which is equivalent to that present in a mixture of a single hiPSC and 5.0×10⁴ RPE cells. Our findings provide highly sensitive and quantitative in vitro assays essential for facilitating safety profiling of hiPSC-derived products for future regenerative medicine research.

  11. Dorzolamide increases retinal oxygen tension after branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Noergaard, Michael Hove; Bach-Holm, Daniella; Scherfig, Erik

    2008-01-01

    To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs.......To study the effect of dorzolamide on the preretinal oxygen tension (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion (BRVO) in pigs....

  12. Identifying Spatial Units of Human Occupation in the Brazilian Amazon Using Landsat and CBERS Multi-Resolution Imagery

    Directory of Open Access Journals (Sweden)

    Maria Isabel Sobral Escada

    2012-01-01

    Full Text Available Every spatial unit of human occupation is part of a network structuring an extensive process of urbanization in the Amazon territory. Multi-resolution remote sensing data were used to identify and map human presence and activities in the Sustainable Forest District of Cuiabá-Santarém highway (BR-163, west of Pará, Brazil. The limits of spatial units of human occupation were mapped based on digital classification of Landsat-TM5 (Thematic Mapper 5 image (30m spatial resolution. High-spatial-resolution CBERS-HRC (China-Brazil Earth Resources Satellite-High-Resolution Camera images (5 m merged with CBERS-CCD (Charge Coupled Device images (20 m were used to map spatial arrangements inside each populated unit, describing intra-urban characteristics. Fieldwork data validated and refined the classification maps that supported the categorization of the units. A total of 133 spatial units were individualized, comprising population centers as municipal seats, villages and communities, and units of human activities, such as sawmills, farmhouses, landing strips, etc. From the high-resolution analysis, 32 population centers were grouped in four categories, described according to their level of urbanization and spatial organization as: structured, recent, established and dependent on connectivity. This multi-resolution approach provided spatial information about the urbanization process and organization of the territory. It may be extended into other areas or be further used to devise a monitoring system, contributing to the discussion of public policy priorities for sustainable development in the Amazon.

  13. Modelling risk of tick exposure in southern Scandinavia using machine learning techniques, satellite imagery, and human population density maps

    OpenAIRE

    Kjær, Lene Jung; Korslund, L.; Kjelland, V.; Slettan, A.; Andreassen, Å. K.; Paulsen, K. M.; Christensson, M.; Kjellander, P.; Teräväinen, M.; Soleng, A.; Edgar, K. S.; Lindstedt, H. H.; Schou, Kirstine Klitgaard; Bødker, Rene

    2017-01-01

    Vector-borne diseases such as Lyme disease and tick-borne encephalitis have become more common in recent decades and present a real health problem in many parts of Europe. Risk assessment, control, and prevention of these diseases require a better understanding of vector abundance as well as risk factors determining human exposure to ticks. There is a great need for analyses and models that can predict how vectors and their associated diseases are distributed and how this relates to high risk...

  14. Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

    DEFF Research Database (Denmark)

    Fanelli, Giorgia; Gonzalez-Cordero, Anai; Gardner, Peter J

    2017-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness and is associated with complement dysregulation. The disease is a potential target for stem cell therapy but success is likely to be limited by the inflammatory response. We investigated the innate immune properties of human ind...

  15. Identifying Potential Areas of Human Zika Infection in the City of Los Angeles, California by Use of Remote Sensing Imagery

    Science.gov (United States)

    Lee, J.

    2017-12-01

    As of April 2017, California is the third most prevalent state on the United States for Zika Infection and Southern California has an ever growing population of Aedes mosquitos. Zika is a disease which poses a significant risk to humans and other mammals due to its effects on pregnancy. This emerging disease is highly contagious due to its spread of infection primarily by Aedes aegypti mosquitos. Aedes mosquitos are able to breed in small rain collecting containers which allow the species to persevere in urban and semi urban environments. We hope to identify potential areas with risk of human infection within Los Angeles and its surrounding areas. This study integrates remote sensing, GIS, statistical, and environmental techniques to study favorable habitats for this particular species of mosquitos and their larvae. The study of the geographic and landscape factors which promote the larvae development allow for the disease spread to be analyzed and modeled. There are several goals in the development of this study. These include the coordination of statistical data with local epidemiology departments, identify workflows to improve efficiency, create models which can be utilized for disease prevention, and identify geographic risk factors for the spread of Zika.

  16. Genetic determinants of hyaloid and retinal vasculature in zebrafish

    Directory of Open Access Journals (Sweden)

    Hyde David R

    2007-10-01

    Full Text Available Abstract Background The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish. Results We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO, subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development. Conclusion Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.

  17. Hyperglycemia Induces Toll-Like Receptor-2 and -4 Expression and Activity in Human Microvascular Retinal Endothelial Cells: Implications for Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Uthra Rajamani

    2014-01-01

    Full Text Available Diabetic retinopathy (DR causes visual impairment in working age adults and hyperglycemia-mediated inflammation is central in DR. Toll-like receptors (TLRs play a key role in innate immune responses and inflammation. However, scanty data is available on their role in DR. Hence, in this study, we examined TLR2 and TLR4 mRNA and protein expression and activity in hyperglycemic human retinal endothelial cells (HMVRECs. HMVRECs were treated with hyperglycemia (HG or euglycemia and mRNA and protein levels of TLR-2, TLR-4, MyD88, IRF3, and TRIF as well as NF-κB p65 activation were measured. IL-8, IL-1β, TNF-α and MCP-1, ICAM-1, and VCAM-1 as well as monocyte adhesion to HMVRECs were also assayed. HG (25 mM significantly induced TLR2 and TLR4 mRNA and protein in HMVRECs. It also increased both MyD88 and non-MyD88 pathways, nuclear factor-κB (NF-κB, biomediators, and monocyte adhesion. This inflammation was attenuated by TLR-4 or TLR-2 inhibition, and dual inhibition by a TLR inhibitory peptide as well as TLR2 and 4 siRNA. Additionally, antioxidant treatment reduced TLR-2 and TLR4 expression and downstream inflammatory markers. Collectively, our novel data suggest that hyperglycemia induces TLR-2 and TLR-4 activation and downstream signaling mediating increased inflammation possibly via reactive oxygen species (ROS and could contribute to DR.

  18. TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    International Nuclear Information System (INIS)

    Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin; Yao, Jin

    2012-01-01

    Highlights: ► TNF-α induces MMP-9 expression and secretion to promote RPE cell migration. ► MAPK activation is not critical for TNF-α-induced MMP-9 expression. ► Akt and mTORC1 signaling mediate TNF-α-induced MMP-9 expression. ► SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-α. -- Abstract: Tumor necrosis factor-alpha (TNF-α) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-α promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-α-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-α-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-α promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  19. The effect of culture density and proliferation rate on the expression of ouabain-sensitive Na/K ATPase pumps in cultured human retinal pigment epithelium

    International Nuclear Information System (INIS)

    Burke, J.M.; Jaffe, G.J.; Brzeski, C.M.

    1991-01-01

    The number and activity of ouabain-sensitive Na/K ATPase pumps expressed by many cell types in vitro, including human retinal pigment epithelial cells (RPE), have been shown to decline with increasing culture density. Cell proliferation also declined as cultures became dense so it was unclear if pump number was modulated by cell proliferation or culture confluency. By exposing RPE cultures to various feeding regimens, using culture medium containing or lacking serum, it was possible to produce RPE cultures with a range of culture densities and growth rates. These were analyzed for proliferative activity by quantifying [ 3 H]thymidine incorporation and for Na/K ATPase pump number by measuring specific [ 3 H]ouabain binding. The results suggest that pump number is modulated by culture density and, further, that the density-dependent regulation of pump number requires serum. Although density-dependent modulation of culture growth is also serum requiring, cell proliferation and pump number did not appear to be related; cultures of similar density which differed significantly in growth rate had similar numbers of pumps. The view that elevated numbers of pumps were not necessarily found in proliferating cells was further supported by qualitative examination of radioautographs of cells dually labeled with [ 3 H]thymidine and [ 3 H]ouabain. Cycling cells which had [ 3 H]thymidine-labeled nuclei did not have notably higher labeling with [ 3 H]ouabain. However, [ 3 H]ouabain labeling, as an indicator of pump site number and distribution, did vary among cells in an RPE population and also within individual cells. This latter observation suggests that unpolarized RPE cells in sparse cultures may have regionally different requirements for ionic regulation

  20. The effect of culture density and proliferation rate on the expression of ouabain-sensitive Na/K ATPase pumps in cultured human retinal pigment epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Burke, J.M.; Jaffe, G.J.; Brzeski, C.M. (Medical College of Wisconsin, Milwaukee (USA))

    1991-06-01

    The number and activity of ouabain-sensitive Na/K ATPase pumps expressed by many cell types in vitro, including human retinal pigment epithelial cells (RPE), have been shown to decline with increasing culture density. Cell proliferation also declined as cultures became dense so it was unclear if pump number was modulated by cell proliferation or culture confluency. By exposing RPE cultures to various feeding regimens, using culture medium containing or lacking serum, it was possible to produce RPE cultures with a range of culture densities and growth rates. These were analyzed for proliferative activity by quantifying ({sup 3}H)thymidine incorporation and for Na/K ATPase pump number by measuring specific ({sup 3}H)ouabain binding. The results suggest that pump number is modulated by culture density and, further, that the density-dependent regulation of pump number requires serum. Although density-dependent modulation of culture growth is also serum requiring, cell proliferation and pump number did not appear to be related; cultures of similar density which differed significantly in growth rate had similar numbers of pumps. The view that elevated numbers of pumps were not necessarily found in proliferating cells was further supported by qualitative examination of radioautographs of cells dually labeled with ({sup 3}H)thymidine and ({sup 3}H)ouabain. Cycling cells which had ({sup 3}H)thymidine-labeled nuclei did not have notably higher labeling with ({sup 3}H)ouabain. However, ({sup 3}H)ouabain labeling, as an indicator of pump site number and distribution, did vary among cells in an RPE population and also within individual cells. This latter observation suggests that unpolarized RPE cells in sparse cultures may have regionally different requirements for ionic regulation.

  1. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  2. Stem Cell Therapies in Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Aakriti Garg

    2017-02-01

    Full Text Available Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

  3. Differential diagnosis of retinal vasculitis.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Herbort, Carl P; Tabbara, Khalid F

    2009-10-01

    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.

  4. Intrasurgical Human Retinal Imaging With Manual Instrument Tracking Using a Microscope-Integrated Spectral-Domain Optical Coherence Tomography Device.

    Science.gov (United States)

    Hahn, Paul; Carrasco-Zevallos, Oscar; Cunefare, David; Migacz, Justin; Farsiu, Sina; Izatt, Joseph A; Toth, Cynthia A

    2015-07-01

    To characterize the first in-human intraoperative imaging using a custom prototype spectral-domain microscope-integrated optical coherence tomography (MIOCT) device during vitreoretinal surgery with instruments in the eye. Under institutional review board approval for a prospective intraoperative study, MIOCT images were obtained at surgical pauses with instruments held static in the vitreous cavity and then concurrently with surgical maneuvers. Postoperatively, MIOCT images obtained at surgical pauses were compared with images obtained with a high-resolution handheld spectral-domain OCT (HHOCT) system with objective endpoints, including acquisition of images acceptable for analysis and identification of predefined macular morphologic or pathologic features. Human MIOCT images were successfully obtained before incision and during pauses in surgical maneuvers. MIOCT imaging confirmed preoperative diagnoses, such as epiretinal membrane, full-thickness macular hole, and vitreomacular traction and demonstrated successful achievement of surgical goals. MIOCT and HHOCT images obtained at surgical pauses in two cohorts of five patients were comparable with greater than or equal to 80% correlation in 80% of patients. Real-time video-imaging concurrent with surgical manipulations enabled, for the first time using this device, visualization of dynamic instrument-retina interaction with targeted OCT tracking. MIOCT is successful for imaging at surgical pauses and for real-time image guidance with implementation of targeted OCT tracking. Even faster acquisition speeds are currently being developed with incorporation of a swept-source MIOCT engine. Further refinements and investigations will be directed toward continued integration for real-time volumetric imaging of surgical maneuvers. Ongoing development of seamless MIOCT systems will likely transform surgical visualization, approaches, and decision-making.

  5. Retinal Detachment Vision Simulator

    Science.gov (United States)

    ... Feb 20, 2018 Gene Therapy May Be a Game-Changer for People With Inherited Retinal Disease Dec 19, 2017 ... the Academy Jobs at the Academy Financial Relationships with Industry Medical Disclaimer Privacy Policy Terms of Service For ...

  6. Learning about Retinitis Pigmentosa

    Science.gov (United States)

    Skip to main content Learning about Retinitis Pigmentosa Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  7. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy

    NARCIS (Netherlands)

    Richards, Anna; van den Maagdenberg, Arn M. J. M.; Jen, Joanna C.; Kavanagh, David; Bertram, Paula; Spitzer, Dirk; Liszewski, M. Kathryn; Barilla-LaBarca, Maria-Louise; Terwindt, Gisela M.; Kasai, Yumi; McLellan, Mike; Grand, Mark Gilbert; Vanmolkot, Kaate R. J.; de Vries, Boukje; Wan, Jijun; Kane, Michael J.; Mamsa, Hafsa; Schäfer, Ruth; Stam, Anine H.; Haan, Joost; de Jong, Paulus T. V. M.; Storimans, Caroline W.; van Schooneveld, Mary J.; Oosterhuis, Jendo A.; Gschwendter, Andreas; Dichgans, Martin; Kotschet, Katya E.; Hodgkinson, Suzanne; Hardy, Todd A.; Delatycki, Martin B.; Hajj-Ali, Rula A.; Kothari, Parul H.; Nelson, Stanley F.; Frants, Rune R.; Baloh, Robert W.; Ferrari, Michel D.; Atkinson, John P.

    2007-01-01

    Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease

  8. Identification of a 2 Mb human ortholog of Drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa.

    NARCIS (Netherlands)

    Collin, R.W.J.; Littink, K.W.; Klevering, B.J.; Born, L.I. van den; Koenekoop, R.K.; Zonneveld-Vrieling, M.N.; Blokland, E.A.W.; Strom, T.M.; Hoyng, C.B.; Hollander, A.I. den; Cremers, F.P.M.

    2008-01-01

    In patients with autosomal-recessive retinitis pigmentosa (arRP), homozygosity mapping was performed for detection of regions harboring genes that might be causative for RP. In one affected sib pair, a shared homozygous region of 5.0 Mb was identified on chromosome 6, within the RP25 locus. One of

  9. Towards a Completely Implantable, Light-Sensitive Intraocular Retinal Prosthesis

    National Research Council Canada - National Science Library

    Humayun, M

    2001-01-01

    .... Previous studies have established the feasibility of the retinal prosthesis. Short-term tests in blind humans have shown that degenerated retina will respond to light in a way that is consistent with form vision...

  10. Coastal California Digital Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This digital ortho-imagery dataset is a survey of coastal California. The project area consists of approximately 3774 square miles. The project design of the digital...

  11. NOAA Emergency Response Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The imagery posted on this site is in response to natural disasters. The aerial photography missions were conducted by the NOAA Remote Sensing Division. The majority...

  12. Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons

    Directory of Open Access Journals (Sweden)

    Hyoung-Tai Kim

    2015-11-01

    Full Text Available OTX2 (orthodenticle homeobox 2 haplodeficiency causes diverse defects in mammalian visual systems ranging from retinal dysfunction to anophthalmia. We find that the retinal dystrophy of Otx2+/GFP heterozygous knockin mice is mainly due to the loss of bipolar cells and consequent deficits in retinal activity. Among bipolar cell types, OFF-cone bipolar subsets, which lack autonomous Otx2 gene expression but receive Otx2 proteins from photoreceptors, degenerate most rapidly in Otx2+/GFP mouse retinas, suggesting a neuroprotective effect of the imported Otx2 protein. In support of this hypothesis, retinal dystrophy in Otx2+/GFP mice is prevented by intraocular injection of Otx2 protein, which localizes to the mitochondria of bipolar cells and facilitates ATP synthesis as a part of mitochondrial ATP synthase complex. Taken together, our findings demonstrate a mitochondrial function for Otx2 and suggest a potential therapeutic application of OTX2 protein delivery in human retinal dystrophy.

  13. Automatic Detection of Retinal Exudates using a Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Nualsawat HIRANSAKOLWONG

    2013-02-01

    Full Text Available Retinal exudates are among the preliminary signs of diabetic retinopathy, a major cause of vision loss in diabetic patients. Correct and efficient screening of exudates is very expensive in professional time and may cause human error. Nowadays, the digital retinal image is frequently used to follow-up and diagnoses eye diseases. Therefore, the retinal image is crucial and essential for experts to detect exudates. Unfortunately, it is a normal situation that retinal images in Thailand are poor quality images. In this paper, we present a series of experiments on feature selection and exudates classification using the support vector machine classifiers. The retinal images are segmented following key preprocessing steps, i.e., color normalization, contrast enhancement, noise removal and color space selection. On data sets of poor quality images, sensitivity, specificity and accuracy is 94.46%, 89.52% and 92.14%, respectively.

  14. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    Science.gov (United States)

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-08-10

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. 2016 BMJ Publishing Group Ltd.

  15. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Tadao Maeda

    2013-07-01

    Full Text Available The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT and retinal pigment epithelium-specific 65-kDa protein (RPE65 known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA and retinitis pigmentosa (RP. Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

  16. A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Junming Wang

    Full Text Available c-Jun, c-Jun N-terminal kinase(JNK and endothelin B (ETB receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP. In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE. The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression

  17. CERKL knockdown causes retinal degeneration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Marina Riera

    Full Text Available The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration.

  18. Retinal shows its true colours

    DEFF Research Database (Denmark)

    Coughlan, N. J.A.; Adamson, B. D.; Gamon, L.

    2015-01-01

    Retinal is one of Nature's most important and widespread chromophores, exhibiting remarkable versatility in its function and spectral response, depending on its protein environment. Reliable spectroscopic and photochemical data for the isolated retinal molecule are essential for calibrating theor...

  19. Retinal findings in membranoproliferative glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2017-09-01

    Conclusions and importance: Drusen remain the ocular stigmata for MPGN occuring at an early age. The retinal disease is progressive with gradual thickening of Bruch's membrane and occurrence of retinal pigment epithelium detachment.

  20. Application of stem cell-derived retinal pigmented epithelium in retinal degenerative diseases: present and future

    Directory of Open Access Journals (Sweden)

    Mingyue Luo

    2018-01-01

    Full Text Available As a constituent of blood-retinal barrier and retinal outer segment (ROS scavenger, retinal pigmented epithelium (RPE is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application.

  1. Application of stem cell-derived retinal pigmented epithelium in retinal degenerative diseases: present and future.

    Science.gov (United States)

    Luo, Mingyue; Chen, Youxin

    2018-01-01

    As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE) is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE) especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application.

  2. Measuring Creative Imagery Abilities

    Directory of Open Access Journals (Sweden)

    Dorota M. Jankowska

    2015-10-01

    Full Text Available Over the decades, creativity and imagination research developed in parallel, but they surprisingly rarely intersected. This paper introduces a new theoretical model of creative imagination, which bridges creativity and imagination research, as well as presents a new psychometric instrument, called the Test of Creative Imagery Abilities (TCIA, developed to measure creative imagery abilities understood in accordance with this model. Creative imagination is understood as constituted by three interrelated components: vividness (the ability to create images characterized by a high level of complexity and detail, originality (the ability to produce unique imagery, and transformativeness (the ability to control imagery. TCIA enables valid and reliable measurement of these three groups of abilities, yielding the general score of imagery abilities and at the same time making profile analysis possible. We present the results of eight studies on a total sample of more than 1,700 participants, showing the factor structure of TCIA using confirmatory factor analysis, as well as provide data confirming this instrument’s validity and reliability. The availability of TCIA for interested researchers may result in new insights and possibilities of integrating the fields of creativity and imagination science.

  3. Probabilistic retinal vessel segmentation

    Science.gov (United States)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  4. Sector retinitis pigmentosa.

    Science.gov (United States)

    Van Woerkom, Craig; Ferrucci, Steven

    2005-05-01

    Retinitis pigmentosa (RP) is one of the most common hereditary retinal dystrophies and causes of visual impairment affecting all age groups. The reported incidence varies, but is considered to be between 1 in 3,000 to 1 in 7,000. Sector retinitis pigmentosa is an atypical form of RP that is characterized by regionalized areas of bone spicule pigmentation, usually in the inferior quadrants of the retina. A 57-year-old Hispanic man with a history of previously diagnosed retinitis pigmentosa came to the clinic with a longstanding symptom of decreased vision at night. Bone spicule pigmentation was found in the nasal and inferior quadrants in each eye. He demonstrated superior and temporal visual-field loss corresponding to the areas of the affected retina. Clinical measurements of visual-field loss, best-corrected visual acuity, and ophthalmoscopic appearance have remained stable during the five years the patient has been followed. Sector retinitis pigmentosa is an atypical form of RP that is characterized by bilateral pigmentary retinopathy, usually isolated to the inferior quadrants. The remainder of the retina appears clinically normal, although studies have found functional abnormalities in these areas as well. Sector RP is generally considered a stationary to slowly progressive disease, with subnormal electro-retinogram findings and visual-field defects corresponding to the involved retinal sectors. Management of RP is very difficult because there are no proven methods of treatment. Studies have shown 15,000 IU of vitamin A palmitate per day may slow the progression, though this result is controversial. Low vision rehabilitation, long wavelength pass filters, and pedigree counseling remain the mainstay of management.

  5. LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.

    Science.gov (United States)

    Pelkonen, Laura; Sato, Kazuki; Reinisalo, Mika; Kidron, Heidi; Tachikawa, Masanori; Watanabe, Michitoshi; Uchida, Yasuo; Urtti, Arto; Terasaki, Tetsuya

    2017-03-06

    The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP). Among 41 studied transporters, 16 proteins were expressed in hfRPE and 13 in ARPE19 cells. MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, LAT1, and MATE1 proteins were detected in both cell lines within 4-fold differences. MPR7, OAT2 and RFC1 were detected in the hfRPE cells, but their expression levels were below the limit of quantification in ARPE19 cells. PCFT was detected in both studied cell lines, but the expression was over 4-fold higher in hfRPE cells. MCT1, MCT4, MRP4, and Na + /K + ATPase were upregulated in the ARPE19 cell line showing over 4-fold differences in the quantitative expression values. Expression levels of 25 transporters were below the limit of quantification in both cell models. In conclusion, we present the first systematic and quantitative study on transporter protein expression in the plasma membranes of ARPE19 and hfRPE cells. Overall, transporter expression in the ARPE19 and hfRPE cells correlated well and the absolute expression levels were similar, but not identical. The presented quantitative expression levels could be a useful basis for further studies on drug permeation in the outer blood-retinal barrier.

  6. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    Directory of Open Access Journals (Sweden)

    Aaron H Fronk

    2016-07-01

    Full Text Available The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.

  7. NAIP 2015 Imagery Feedback Map

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — The NAIP 2015 Imagery Feedback map allows users to make comments and observations about the quality of the 2015 National Agriculture Imagery Program (NAIP)...

  8. NAIP 2017 Imagery Feedback Map

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — The NAIP 2017 Imagery Feedback map allows users to make comments and observations about the quality of the 2017 National Agriculture Imagery Program (NAIP)...

  9. Gestures maintain spatial imagery.

    Science.gov (United States)

    Wesp, R; Hesse, J; Keutmann, D; Wheaton, K

    2001-01-01

    Recent theories suggest alternatives to the commonly held belief that the sole role of gestures is to communicate meaning directly to listeners. Evidence suggests that gestures may serve a cognitive function for speakers, possibly acting as lexical primes. We observed that participants gestured more often when describing a picture from memory than when the picture was present and that gestures were not influenced by manipulating eye contact of a listener. We argue that spatial imagery serves a short-term memory function during lexical search and that gestures may help maintain spatial images. When spatial imagery is not necessary, as in conditions of direct visual stimulation, reliance on gestures is reduced or eliminated.

  10. Hypnagogic imagery and EEG activity.

    Science.gov (United States)

    Hayashi, M; Katoh, K; Hori, T

    1999-04-01

    The relationships between hypnagogic imagery and EEG activity were studied. 7 subjects (4 women and 3 men) reported the content of hypnagogic imagery every minute and the hypnagogic EEGs were classified into 5 stages according to Hori's modified criteria. The content of the hypnagogic imagery changed as a function of the hypnagogic EEG stages.

  11. Nanomaterials and Retinal Toxicity

    Science.gov (United States)

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  12. Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization

    Directory of Open Access Journals (Sweden)

    Takahito Nakama

    2017-03-01

    Full Text Available Retinal neovascularization (NV due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.

  13. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about 500...

  14. Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

    Science.gov (United States)

    Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

    2016-01-01

    Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

  15. Stem cell therapy for retinal diseases

    Science.gov (United States)

    Garcia, José Mauricio; Mendonça, Luisa; Brant, Rodrigo; Abud, Murilo; Regatieri, Caio; Diniz, Bruno

    2015-01-01

    In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt’s dystrophy, and patients with geographic atrophy, providing good outcomes. This study’s intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients’ vision, and, finally, approaching future directions and challenges for the treatment of several conditions. PMID:25621115

  16. Peripapillary retinal thermal coagulation following electrical injury

    Directory of Open Access Journals (Sweden)

    Manjari Tandon

    2013-01-01

    Full Text Available In this study, we have presented the case report of a 20 year old boy who suffered an electric injury shock, following which he showed peripapillary retinal opacification and increased retinal thickening that subsequently progressed to retinal atrophy. The fluorescein angiogram revealed normal retinal circulation, thus indicating thermal damage to retina without any compromise to retinal circulation.

  17. Peripheral retinal degenerations and the risk of retinal detachment.

    Science.gov (United States)

    Lewis, Hilel

    2003-07-01

    To review the degenerative diseases of the peripheral retina in relationship with the risk to develop a rhegmatogenous retinal detachment and to present recommendations for use in eyes at increased risk of developing a retinal detachment. Focused literature review and author's clinical experience. Retinal degenerations are common lesions involving the peripheral retina, and most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and, rarely, zonular traction tufts, can result in a rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic therapy; however, adequate studies have not been performed to date. Well-designed, prospective, randomized clinical studies are necessary to determine the benefit-risk ratio of prophylactic treatment. In the meantime, the evidence available suggests that most of the peripheral retinal degenerations should not be treated except in rare, high-risk situations.

  18. Retinal stem cells and regeneration of vision system.

    Science.gov (United States)

    Yip, Henry K

    2014-01-01

    The vertebrate retina is a well-characterized model for studying neurogenesis. Retinal neurons and glia are generated in a conserved order from a pool of mutlipotent progenitor cells. During retinal development, retinal stem/progenitor cells (RPC) change their competency over time under the influence of intrinsic (such as transcriptional factors) and extrinsic factors (such as growth factors). In this review, we summarize the roles of these factors, together with the understanding of the signaling pathways that regulate eye development. The information about the interactions between intrinsic and extrinsic factors for retinal cell fate specification is useful to regenerate specific retinal neurons from RPCs. Recent studies have identified RPCs in the retina, which may have important implications in health and disease. Despite the recent advances in stem cell biology, our understanding of many aspects of RPCs in the eye remains limited. PRCs are present in the developing eye of all vertebrates and remain active in lower vertebrates throughout life. In mammals, however, PRCs are quiescent and exhibit very little activity and thus have low capacity for retinal regeneration. A number of different cellular sources of RPCs have been identified in the vertebrate retina. These include PRCs at the retinal margin, pigmented cells in the ciliary body, iris, and retinal pigment epithelium, and Müller cells within the retina. Because PRCs can be isolated and expanded from immature and mature eyes, it is possible now to study these cells in culture and after transplantation in the degenerated retinal tissue. We also examine current knowledge of intrinsic RPCs, and human embryonic stems and induced pluripotent stem cells as potential sources for cell transplant therapy to regenerate the diseased retina. Copyright © 2013 Wiley Periodicals, Inc.

  19. Training visual imagery: Improvements of metacognition, but not imagery strength

    Directory of Open Access Journals (Sweden)

    Rosanne Lynn Rademaker

    2012-07-01

    Full Text Available Visual imagery has been closely linked to brain mechanisms involved in perception. Can visual imagery, like visual perception, improve by means of training? Previous research has demonstrated that people can reliably evaluate the vividness of single episodes of sensory imagination – might the metacognition of imagery also improve over the course of training? We had participants imagine colored Gabor patterns for an hour a day, over the course of five consecutive days, and again two weeks after training. Participants rated the subjective vividness and effort of their mental imagery on each trial. The influence of imagery on subsequent binocular rivalry dominance was taken as our measure of imagery strength. We found no overall effect of training on imagery strength. Training did, however, improve participant’s metacognition of imagery. Trial-by-trial ratings of vividness gained predictive power on subsequent rivalry dominance as a function of training. These data suggest that, while imagery strength might be immune to training in the current context, people’s metacognitive understanding of mental imagery can improve with practice.

  20. Platform image processing to study the structural properties of retinal vessel

    Directory of Open Access Journals (Sweden)

    Miguel Ángel MERCHÁN

    2013-05-01

    Full Text Available This paper presents a technological platform specialized in assessing retinal vessel caliber and describing the relationship of the results obtained to cardiovascular risk. Retinal circulation is an area of active research by numerous groups, and there is general experimental agreement on the analysis of the patterns of the retinal blood vessels in the normal human retina. The development of automated tools designed to improve performance and decrease interobserver variability, therefore, appears necessary. 

  1. Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

    OpenAIRE

    Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T. Michael; Baehr, Wolfgang; Ding, Xi-Qin

    2014-01-01

    Photoreceptors degenerate in a wide array of hereditary retinal diseases and age-related macular degeneration. There is currently no treatment available for retinal degenerations. While outnumbered roughly 20:1 by rods in the human retina, it is the cones that mediate color vision and visual acuity, and their survival is critical for vision. In this communication, we investigate whether thyroid hormone (TH) signaling affects cone viability in retinal degeneration mouse models. TH signaling is...

  2. Retinitis pigmentosa and deafness.

    OpenAIRE

    Mills, R P; Calver, D M

    1987-01-01

    Seventeen patients with retinitis pigmentosa (RP) have been investigated audiologically. Of 9 found to have a significant hearing loss, 6 were examples of Usher's syndrome; these patients had a cochlear pattern of hearing loss. The other 3 were examples of Senior's syndrome, Kearne-Sayre syndrome and Lawrence-Moon-Biedle syndrome respectively. Two of these patients had absent stapedius reflexes. It is suggested that patients with different RP-deafness syndromes may have lesions in different p...

  3. Retinal Protection and Distribution of Curcumin in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Chiara B. M. Platania

    2018-06-01

    Full Text Available Diabetic retinopathy (DR, a secondary complication of diabetes, is a leading cause of irreversible blindness accounting for 5% of world blindness cases in working age. Oxidative stress and inflammation are considered causes of DR. Curcumin, a product with anti-oxidant and anti-inflammatory properties, is currently proposed as oral supplementation therapy for retinal degenerative diseases, including DR. In this study we predicted the pharmacodynamic profile of curcumin through an in silico approach. Furthermore, we tested the anti-oxidant and anti-inflammatory activity of curcumin on human retinal pigmented epithelial cells exposed to oxidative stress, human retinal endothelial and human retinal pericytes (HRPCs cultured with high glucose. Because currently marketed curcumin nutraceutical products have not been so far evaluated for their ocular bioavailability; we assessed retinal distribution of curcumin, following oral administration, in rabbit eye. Curcumin (10 μM decreased significantly (p < 0.01 ROS concentration and TNF-α release in retinal pigmented epithelial cells and retinal endothelial cells, respectively. The same curcumin concentration significantly (p < 0.01 protected retinal pericytes from high glucose damage as assessed by cell viability and LDH release. Among the tested formulations, only that containing a hydrophilic carrier provided therapeutic levels of curcumin in rabbit retina. In conclusion, our data suggest that curcumin, when properly formulated, may be of value in clinical practice to manage retinal diseases.

  4. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2017-09-13

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  5. Outcomes in bullous retinal detachment

    Directory of Open Access Journals (Sweden)

    Sarah P. Read

    2017-06-01

    Conclusions and importance: GRTs are an uncommon cause of retinal detachment. While pars plana vitrectomy with tamponade is standard in GRT management, there is variability in the use of scleral buckling and PFO in these cases. This is in contrast to retinal dialysis where scleral buckle alone can yield favorable results. Though a baseball ocular trauma is common, retinal involvement is rare compared to other sports injuries such as those occurring with tennis, soccer and golf. Sports trauma remains an important cause of retinal injury and patients should be counseled on the need for eye protection.

  6. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

    Directory of Open Access Journals (Sweden)

    Cheryl A Arcinue

    Full Text Available To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula compared with age-matched HIV-negative controls.Cohort of patients with known HIV under CART (combination Antiretroviral Therapy treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT to assess retinal layers and retinal thickness.Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior, the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2. A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea. We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer was also significantly thickened in all the different locations scanned compared with HIV-negative controls.Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

  7. Planning, preparation, execution, and imagery of volitional action.

    Science.gov (United States)

    Deecke, L

    1996-03-01

    There are different motor sets, which a human subject can be in or act from: he or she can be in a self-initiated voluntary movement set (action) or in a response set (re-action). Also, imagery sets are available that are necessary for the acquisition and practice of skill. Most important are such imagery sets for rehearsal in theatre, dance, music, sports, combat, etc.

  8. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy.

    Science.gov (United States)

    Uddin, Md Imam; Evans, Stephanie M; Craft, Jason R; Capozzi, Megan E; McCollum, Gary W; Yang, Rong; Marnett, Lawrence J; Uddin, Md Jashim; Jayagopal, Ashwath; Penn, John S

    2016-08-05

    Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs.

  9. Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside

    Directory of Open Access Journals (Sweden)

    Søren Leer Blindbæk

    2017-01-01

    Full Text Available The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes.

  10. Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside

    Science.gov (United States)

    Blindbæk, Søren Leer; Torp, Thomas Lee; Lundberg, Kristian; Soelberg, Kerstin; Vergmann, Anna Stage; Poulsen, Christina Døfler; Frydkjaer-Olsen, Ulrik; Broe, Rebecca; Rasmussen, Malin Lundberg; Wied, Jimmi; Lind, Majbrit; Vestergaard, Anders Højslet; Peto, Tunde

    2017-01-01

    The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes. PMID:28491870

  11. Evaluation of RPE65, CRALBP, VEGF, CD68, and tyrosinase gene expression in human retinal pigment epithelial cells cultured on amniotic membrane.

    Science.gov (United States)

    Akrami, Hassan; Soheili, Zahra-Soheila; Sadeghizadeh, Majid; Khalooghi, Keynoush; Ahmadieh, Hamid; Kanavi, Mojgan Rezaie; Samiei, Shahram; Pakravesh, Jalil

    2011-06-01

    The retinal pigment epithelium (RPE) plays a key role in the maintenance of the normal functions of the retina. Tissue engineering using amniotic membrane as a substrate to culture RPE cells may provide a promising new strategy to replace damaged RPE. We established a method of culturing RPE cells over the amniotic membrane as a support for their growth and transplantation. The transcription of specific genes involved in cellular function of native RPE, including RPE65, CRALBP, VEGF, CD68, and tyrosinase, were then measured using quantitative real-time PCR. Data showed a considerable increase in transcription of RPE65, CD68, and VEGF in RPE cells cultured on amniotic membrane. The amounts of CRALBP and tyrosinase transcripts were not affected. This may simply indicate that amniotic membrane restricted dedifferentiation of RPE cells in culture. The results suggest that amniotic membrane may be considered as an elective biological substrate for RPE cell culture.

  12. Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

    Directory of Open Access Journals (Sweden)

    Chen CL

    2017-01-01

    Full Text Available Ching-Long Chen,1,2 Yi-Hao Chen,1,2 Ming-Cheng Tai,2 Chang-Min Liang,2 Da-Wen Lu,1,2 Jiann-Torng Chen1,2 1Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 2Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract: Proliferative vitreoretinopathy (PVR is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF-β2-induced epithelial-to-mesenchymal transition (EMT plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-β2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1 and caused an increase of alpha-smooth muscle actin expression in TGF-β2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-β2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction – assessed by collagen matrix contraction assay – and suppressed the phosphorylation of Smad2 and Smad3 in TGF-β2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the prevention of PVR. Keywords: resveratrol, epithelial-to-mesenchymal transition, proliferative vitreoretinopathy, transforming growth factor-β2, retinal pigment epithelial cells

  13. Barrier properties of cultured retinal pigment epithelium.

    Science.gov (United States)

    Rizzolo, Lawrence J

    2014-09-01

    The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Kinesthetic imagery of musical performance.

    Science.gov (United States)

    Lotze, Martin

    2013-01-01

    Musicians use different kinds of imagery. This review focuses on kinesthetic imagery, which has been shown to be an effective complement to actively playing an instrument. However, experience in actual movement performance seems to be a requirement for a recruitment of those brain areas representing movement ideation during imagery. An internal model of movement performance might be more differentiated when training has been more intense or simply performed more often. Therefore, with respect to kinesthetic imagery, these strategies are predominantly found in professional musicians. There are a few possible reasons as to why kinesthetic imagery is used in addition to active training; one example is the need for mental rehearsal of the technically most difficult passages. Another reason for mental practice is that mental rehearsal of the piece helps to improve performance if the instrument is not available for actual training as is the case for professional musicians when they are traveling to various appearances. Overall, mental imagery in musicians is not necessarily specific to motor, somatosensory, auditory, or visual aspects of imagery, but integrates them all. In particular, the audiomotor loop is highly important, since auditory aspects are crucial for guiding motor performance. All these aspects result in a distinctive representation map for the mental imagery of musical performance. This review summarizes behavioral data, and findings from functional brain imaging studies of mental imagery of musical performance.

  15. Application of morphological bit planes in retinal blood vessel extraction.

    Science.gov (United States)

    Fraz, M M; Basit, A; Barman, S A

    2013-04-01

    The appearance of the retinal blood vessels is an important diagnostic indicator of various clinical disorders of the eye and the body. Retinal blood vessels have been shown to provide evidence in terms of change in diameter, branching angles, or tortuosity, as a result of ophthalmic disease. This paper reports the development for an automated method for segmentation of blood vessels in retinal images. A unique combination of methods for retinal blood vessel skeleton detection and multidirectional morphological bit plane slicing is presented to extract the blood vessels from the color retinal images. The skeleton of main vessels is extracted by the application of directional differential operators and then evaluation of combination of derivative signs and average derivative values. Mathematical morphology has been materialized as a proficient technique for quantifying the retinal vasculature in ocular fundus images. A multidirectional top-hat operator with rotating structuring elements is used to emphasize the vessels in a particular direction, and information is extracted using bit plane slicing. An iterative region growing method is applied to integrate the main skeleton and the images resulting from bit plane slicing of vessel direction-dependent morphological filters. The approach is tested on two publicly available databases DRIVE and STARE. Average accuracy achieved by the proposed method is 0.9423 for both the databases with significant values of sensitivity and specificity also; the algorithm outperforms the second human observer in terms of precision of segmented vessel tree.

  16. The circadian response of intrinsically photosensitive retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Andrew J Zele

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGC signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central or intrinsic (retinal network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC and outer retina (cone photoreceptors was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux. Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin retinal ganglion cells mediate this circadian variation.

  17. Retinal astrocytoma in a dog.

    Science.gov (United States)

    Kuroki, Keiichi; Kice, Nathan; Ota-Kuroki, Juri

    2017-09-01

    A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic protein, vimentin, and S-100 and largely negatively for oligodendrocyte transcription factor 2 by immunohistochemistry. The clinical and histopathological features of canine retinal astrocytomas are discussed.

  18. Non-syndromic retinitis pigmentosa

    NARCIS (Netherlands)

    Verbakel, S.K. (Sanne K.); R.A.C. van Huet (Ramon A. C.); C.J.F. Boon (Camiel); A.I. Hollander (Anneke); R.W.J. Collin (Rob); C.C.W. Klaver (Caroline); C. Hoyng (Carel); R. Roepman (Ronald); B.J. Klevering (Jeroen)

    2018-01-01

    textabstractRetinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by the primary degeneration of rod and cone photoreceptors. RP is a leading cause of visual disability, with a worldwide prevalence of 1:4000. Although the majority of RP cases are non-syndromic,

  19. Retinal Imaging and Image Analysis

    Science.gov (United States)

    Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

    2011-01-01

    Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:22275207

  20. Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

    NARCIS (Netherlands)

    Alves, Celso Henrique; Pellissier, Lucie P; Vos, Rogier M; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Seide, Christina; Beck, Susanne C; Klooster, J.; Furukawa, Takahisa; Flannery, John G; Verhaagen, J.; Seeliger, Mathias W; Wijnholds, J.

    2014-01-01

    In humans, the Crumbs homolog-1 (CRB1) gene is mutated in autosomal recessive Leber congenital amaurosis and early-onset retinitis pigmentosa. In mammals, the Crumbs family is composed of: CRB1, CRB2, CRB3A and CRB3B. Recently, we showed that removal of mouse Crb2 from retinal progenitor cells, and

  1. Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

    Science.gov (United States)

    Ruiz-Cruz, Matilde; Alvarado-de la Barrera, Claudia; Ablanedo-Terrazas, Yuria; Reyes-Terán, Gustavo

    2014-07-15

    Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Non-Drug Pain Relief: Imagery

    Science.gov (United States)

    PATIENT EDUCATION patienteducation.osumc.edu Non-Drug Pain Relief: Imagery Relaxation helps lessen tension. One way to help decrease pain is to use imagery. Imagery is using your imagination to create a ...

  3. Spectrophotometric retinal oximetry in pigs

    DEFF Research Database (Denmark)

    Traustason, Sindri; Kiilgaard, Jens Folke; Karlsson, Robert

    2013-01-01

    PURPOSE: To assess the validity of spectrophotometric retinal oximetry, by comparison to blood gas analysis and intra-vitreal measurements of partial pressure of oxygen (pO2). METHODS: Female domestic pigs were used for all experiments (n=8). Oxygen fraction in inspired air was changed using...... a mixture of room air, pure oxygen and pure nitrogen, ranging from 5% to 100% oxygen. Femoral arterial blood gas analysis and retinal oximetry was performed at each level of inspiratory oxygen fraction. Retinal oximetry was performed using a commercial instrument, the Oxymap Retinal Oximeter T1 (Oxymap ehf...... arterial oxygen saturation and the optical density ratio over retinal arteries revealed an approximately linear relationship (R(2) = 0.74, p = 3.4 x 10(-9)). In order to test the validity of applying the arterial calibration to veins, we compared non-invasive oximetry measurements to invasive pO2...

  4. Effects of microgravity on cognition: The case of mental imagery.

    Science.gov (United States)

    Grabherr, Luzia; Mast, Fred W

    2010-01-01

    Human cognitive performance is an important factor for the successful and safe outcome of commercial and non-commercial manned space missions. This article aims to provide a systematic review of studies investigating the effects of microgravity on the cognitive abilities of parabolic or space flight participants due to the absence of the gravito-inertial force. We will focus on mental imagery: one of the best studied cognitive functions. Mental imagery is closely connected to perception and motor behavior. It aids important processes such as perceptual anticipation, problem solving and motor simulation, all of which are critical for space travel. Thirteen studies were identified and classified into the following topics: spatial representations, mental image transformations and motor imagery. While research on spatial representation and mental image transformation continues to grow and specific differences in cognitive functioning between 1 g and 0 g have been observed, motor imagery has thus far received little attention.

  5. Benchmark Imagery FY11 Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pope, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-06-14

    This report details the work performed in FY11 under project LL11-GS-PD06, “Benchmark Imagery for Assessing Geospatial Semantic Extraction Algorithms.” The original LCP for the Benchmark Imagery project called for creating a set of benchmark imagery for verifying and validating algorithms that extract semantic content from imagery. More specifically, the first year was slated to deliver real imagery that had been annotated, the second year to deliver real imagery that had composited features, and the final year was to deliver synthetic imagery modeled after the real imagery.

  6. Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yue; Li, Ge; Wang, Ke; Xie, Ya-Ya; Zhou, Ren-Peng; Meng, Yao; Ding, Ran; Ge, Jin-Fang; Chen, Fei-Hu, E-mail: cfhchina@sohu.com

    2017-03-15

    As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ATPR on APL cells was accompanied with autophagy induction and PML-RARα degradation via activating Notch1 signaling pathway. Moreover, inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNA (siRNA) that targets essential autophagy gene ATG5 abrogated the ATPR-induced cell differentiation. Furthermore, when pretreated with DAPT, a γ-secretase inhibitor, the Notch1 signaling pathway was blocked in APL cells, followed by the reduction of ATPR-induced autophagy and differentiation. Taken together, these results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients. - Highlights: • ATPR induces autophagy in APL cell line NB4 cells. • Autophagy induction is essential for cell differentiation in NB4 cells. • Notch1 signaling is involved in ATPR-induced autophagy and differentiation in NB4 cells.

  7. Neural decoding of visual imagery during sleep.

    Science.gov (United States)

    Horikawa, T; Tamaki, M; Miyawaki, Y; Kamitani, Y

    2013-05-03

    Visual imagery during sleep has long been a topic of persistent speculation, but its private nature has hampered objective analysis. Here we present a neural decoding approach in which machine-learning models predict the contents of visual imagery during the sleep-onset period, given measured brain activity, by discovering links between human functional magnetic resonance imaging patterns and verbal reports with the assistance of lexical and image databases. Decoding models trained on stimulus-induced brain activity in visual cortical areas showed accurate classification, detection, and identification of contents. Our findings demonstrate that specific visual experience during sleep is represented by brain activity patterns shared by stimulus perception, providing a means to uncover subjective contents of dreaming using objective neural measurement.

  8. Imagery Rescripting for Personality Disorders

    Science.gov (United States)

    Arntz, Arnoud

    2011-01-01

    Imagery rescripting is a powerful technique that can be successfully applied in the treatment of personality disorders. For personality disorders, imagery rescripting is not used to address intrusive images but to change the implicational meaning of schemas and childhood experiences that underlie the patient's problems. Various mechanisms that may…

  9. Shades of grey; Assessing the contribution of the magno- and parvocellular systems to neural processing of the retinal input in the human visual system from the influence of neural population size and its discharge activity on the VEP.

    Science.gov (United States)

    Marcar, Valentine L; Baselgia, Silvana; Lüthi-Eisenegger, Barbara; Jäncke, Lutz

    2018-03-01

    Retinal input processing in the human visual system involves a phasic and tonic neural response. We investigated the role of the magno- and parvocellular systems by comparing the influence of the active neural population size and its discharge activity on the amplitude and latency of four VEP components. We recorded the scalp electric potential of 20 human volunteers viewing a series of dartboard images presented as a pattern reversing and pattern on-/offset stimulus. These patterns were designed to vary both neural population size coding the temporal- and spatial luminance contrast property and the discharge activity of the population involved in a systematic manner. When the VEP amplitude reflected the size of the neural population coding the temporal luminance contrast property of the image, the influence of luminance contrast followed the contrast response function of the parvocellular system. When the VEP amplitude reflected the size of the neural population responding to the spatial luminance contrast property the image, the influence of luminance contrast followed the contrast response function of the magnocellular system. The latencies of the VEP components examined exhibited the same behavior across our stimulus series. This investigation demonstrates the complex interplay of the magno- and parvocellular systems on the neural response as captured by the VEP. It also demonstrates a linear relationship between stimulus property, neural response, and the VEP and reveals the importance of feedback projections in modulating the ongoing neural response. In doing so, it corroborates the conclusions of our previous study.

  10. Figurative and symbolic function of animal imagery in packaging ...

    African Journals Online (AJOL)

    This paper sets out to discuss how the Shona and Ndebele people of Zimbabwe make use of animal imagery to refer to human behaviour and habits in various situations. In this context, animal traits are drawn from both domestic and wild animals. A discussion of such a conception of human behaviour shall demonstrate ...

  11. Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury

    International Nuclear Information System (INIS)

    Ren, Luqing; Tao, Jianjian; Chen, Huaicheng; Bian, Yang; Yang, Xi; Chen, Gaozhi; Zhang, Xin; Liang, Guang; Wu, Wencan; Song, Zongming; Wang, Yi

    2017-01-01

    Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury. We confirmed these findings using MD2 knockout mice. Furthermore, we utilized human retinal pigment epithelial cells (ARPE-19 cells) to show that oxidative stress-induced cell death as well as inflammatory response are mediated through MD2. Inhibition of MD2 through a chemical inhibitor or knockdown prevented oxidative stress-induced cell death and expression of inflammatory cytokines. Oxidative stress was found to activate TLR4 in a MD2-dependent manner via increasing the expression of high mobility group box 1. In summary, our study shows that oxidative stress in retinal I/R injury can activate TLR4 signaling via MD2, resulting in induction of inflammatory genes and retinal damage. MD2 may represent an attractive therapeutic target for retinal I/R injury. - Highlights: • MD2 inhibition reduced retinal damage after I/R induction in mice. • TBHP induced TLR4/MD2 binding via increasing HMGB-1 expression. • TLR4/MD2 initiated inflammatory response via activation of MAPKs and NF-κB. • MD2 could be the therapeutic target for the treatment of retinal I/R.

  12. Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Luqing [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Tao, Jianjian; Chen, Huaicheng; Bian, Yang; Yang, Xi [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Chen, Gaozhi; Zhang, Xin; Liang, Guang [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Wencan, E-mail: wuwencan118@163.com [The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Song, Zongming, E-mail: szmeyes@126.com [The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Yi, E-mail: yi.wang1122@wmu.edu.cn [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2017-02-15

    Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury. We confirmed these findings using MD2 knockout mice. Furthermore, we utilized human retinal pigment epithelial cells (ARPE-19 cells) to show that oxidative stress-induced cell death as well as inflammatory response are mediated through MD2. Inhibition of MD2 through a chemical inhibitor or knockdown prevented oxidative stress-induced cell death and expression of inflammatory cytokines. Oxidative stress was found to activate TLR4 in a MD2-dependent manner via increasing the expression of high mobility group box 1. In summary, our study shows that oxidative stress in retinal I/R injury can activate TLR4 signaling via MD2, resulting in induction of inflammatory genes and retinal damage. MD2 may represent an attractive therapeutic target for retinal I/R injury. - Highlights: • MD2 inhibition reduced retinal damage after I/R induction in mice. • TBHP induced TLR4/MD2 binding via increasing HMGB-1 expression. • TLR4/MD2 initiated inflammatory response via activation of MAPKs and NF-κB. • MD2 could be the therapeutic target for the treatment of retinal I/R.

  13. Retinal pigment epithelium culture;a potential source of retinal stem cells.

    Science.gov (United States)

    Akrami, Hassan; Soheili, Zahra-Soheila; Khalooghi, Keynoush; Ahmadieh, Hamid; Rezaie-Kanavi, Mojgan; Samiei, Shahram; Davari, Malihe; Ghaderi, Shima; Sanie-Jahromi, Fatemeh

    2009-07-01

    To establish human retinal pigment epithelial (RPE) cell culture as a source for cell replacement therapy in ocular diseases. Human cadaver globes were used to isolate RPE cells. Each globe was cut into several pieces of a few millimeters in size. After removing the sclera and choroid, remaining tissues were washed in phosphate buffer saline and RPE cells were isolated using dispase enzyme solution and cultured in Dulbecco's Modified Eagle's Medium: Nutrient Mixture F-12 supplemented with 10% fetal calf serum. Primary cultures of RPE cells were established and spheroid colonies related to progenitor/stem cells developed in a number of cultures. The colonies included purely pigmented or mixed pigmented and non-pigmented cells. After multiple cellular passages, several types of photoreceptors and neural-like cells were detected morphologically. Cellular plasticity in RPE cell cultures revealed promising results in terms of generation of stem/progenitor cells from human RPE cells. Whether the spheroids and neural-like retinal cells were directly derived from retinal stem cells or offspring of trans-differentiating or de-differentiating RPE cells remains to be answered.

  14. Prosthetic vision: devices, patient outcomes and retinal research.

    Science.gov (United States)

    Hadjinicolaou, Alex E; Meffin, Hamish; Maturana, Matias I; Cloherty, Shaun L; Ibbotson, Michael R

    2015-09-01

    Retinal disease and its associated retinal degeneration can lead to the loss of photoreceptors and therefore, profound blindness. While retinal degeneration destroys the photoreceptors, the neural circuits that convey information from the eye to the brain are sufficiently preserved to make it possible to restore sight using prosthetic devices. Typically, these devices consist of a digital camera and an implantable neurostimulator. The image sensor in a digital camera has the same spatiotopic arrangement as the photoreceptors of the retina. Therefore, it is possible to extract meaningful spatial information from an image and deliver it via an array of stimulating electrodes directly to the surviving retinal circuits. Here, we review the structure and function of normal and degenerate retina. The different approaches to prosthetic implant design are described in the context of human and preclinical trials. In the last section, we review studies of electrical properties of the retina and its response to electrical stimulation. These types of investigation are currently assessing a number of key challenges identified in human trials, including stimulation efficacy, spatial localisation, desensitisation to repetitive stimulation and selective activation of retinal cell populations. © 2015 The Authors. Clinical and Experimental Optometry © 2015 Optometry Australia.

  15. The Apical Localization of Na+, K+-ATPase in Cultured Human Retinal Pigment Epithelial Cells Depends on Expression of the β2 Subunit.

    Science.gov (United States)

    Lobato-Álvarez, Jorge A; Roldán, María L; López-Murillo, Teresa Del Carmen; González-Ramírez, Ricardo; Bonilla-Delgado, José; Shoshani, Liora

    2016-01-01

    Na + , K + -ATPase, or the Na + pump, is a key component in the maintenance of the epithelial phenotype. In most epithelia, the pump is located in the basolateral domain. Studies from our laboratory have shown that the β 1 subunit of Na + , K + -ATPase plays an important role in this mechanism because homotypic β 1 -β 1 interactions between neighboring cells stabilize the pump in the lateral membrane. However, in the retinal pigment epithelium (RPE), the Na + pump is located in the apical domain. The mechanism of polarization in this epithelium is unclear. We hypothesized that the apical polarization of the pump in RPE cells depends on the expression of its β 2 subunit. ARPE-19 cells cultured for up to 8 weeks on inserts did not polarize, and Na + , K + -ATPase was expressed in the basolateral membrane. In the presence of insulin, transferrin and selenic acid (ITS), ARPE-19 cells cultured for 4 weeks acquired an RPE phenotype, and the Na + pump was visible in the apical domain. Under these conditions, Western blot analysis was employed to detect the β 2 isoform and immunofluorescence analysis revealed an apparent apical distribution of the β 2 subunit. qPCR results showed a time-dependent increase in the level of β 2 isoform mRNA, suggesting regulation at the transcriptional level. Moreover, silencing the expression of the β 2 isoform in ARPE-19 cells resulted in a decrease in the apical localization of the pump, as assessed by the mislocalization of the α 2 subunit in that domain. Our results demonstrate that the apical polarization of Na + , K + -ATPase in RPE cells depends on the expression of the β 2 subunit.

  16. Overexpression of miR-183/-96/-182 triggers neuronal cell fate in Human Retinal Pigment Epithelial (hRPE) cells in culture.

    Science.gov (United States)

    Davari, Maliheh; Soheili, Zahra-Soheila; Samiei, Shahram; Sharifi, Zohreh; Pirmardan, Ehsan Ranaei

    2017-01-29

    miR-183 cluster, composed of miR-183/-96/-182 genes, is highly expressed in the adult retina, particularly in photoreceptors. It involves in development, maturation and normal function of neuroretina. Ectopic overexpression of miR-183/-96/-182 genes was performed to assess reprogramming of hRPE cells. They were amplified from genomic DNA and cloned independently or in tandem configuration into pAAV.MCS vector. hRPE cells were then transfected with the recombinant constructs. Real-Time PCR was performed to measure the expression levels of miR-183/-96/-182 and that of several retina-specific neuronal genes such as OTX2, NRL, PDC and DCT. The transfected cells also were immunocytochemically examined for retina-specific neuronal markers, including Rhodopsin, red opsin, CRX, Thy1, CD73, recoverin and PKCα, to determine the cellular fate of the transfected hRPE cells. Data showed that upon miR-183/-96/-182 overexpression in hRPE cultures, the expression of neuronal genes including OTX2, NRL, PDC and DCT was also upregulated. Moreover, miR-183 cluster-treated hRPE cells were immunoreactive for neuronal markers such as Rhodopsin, red opsin, CRX and Thy1. Both transcriptional and translational upregulation of neuronal genes in miR-183 cluster-treated hRPE cells suggests that in vitro overexpression of miR-183 cluster could trigger reprogramming of hRPE cells to retinal neuron fate. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Deborah A. Ferrington

    2017-10-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness among older adults. It has been suggested that mitochondrial defects in the retinal pigment epithelium (RPE underlies AMD pathology. To test this idea, we developed primary cultures of RPE to ask whether RPE from donors with AMD differ in their metabolic profile compared with healthy age-matched donors. Analysis of gene expression, protein content, and RPE function showed that these cultured cells replicated many of the cardinal features of RPE in vivo. Using the Seahorse Extracellular Flux Analyzer to measure bioenergetics, we observed RPE from donors with AMD exhibited reduced mitochondrial and glycolytic function compared with healthy donors. RPE from AMD donors were also more resistant to oxidative inactivation of these two energy-producing pathways and were less susceptible to oxidation-induced cell death compared with cells from healthy donors. Investigation of the potential mechanism responsible for differences in bioenergetics and resistance to oxidative stress showed RPE from AMD donors had increased PGC1α protein as well as differential expression of multiple genes in response to an oxidative challenge. Based on our data, we propose that cultured RPE from donors phenotyped for the presence or absence of AMD provides an excellent model system for studying “AMD in a dish”. Our results are consistent with the ideas that (i a bioenergetics crisis in the RPE contributes to AMD pathology, and (ii the diseased environment in vivo causes changes in the cellular profile that are retained in vitro.

  18. Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.

    Science.gov (United States)

    Yang, Po-Min; Wu, Zhi-Zhen; Zhang, Yu-Qi; Wung, Being-Sun

    2016-06-15

    Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells. We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA. Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished. The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Vividness of Visual Imagery Depends on the Neural Overlap with Perception in Visual Areas.

    Science.gov (United States)

    Dijkstra, Nadine; Bosch, Sander E; van Gerven, Marcel A J

    2017-02-01

    Research into the neural correlates of individual differences in imagery vividness point to an important role of the early visual cortex. However, there is also great fluctuation of vividness within individuals, such that only looking at differences between people necessarily obscures the picture. In this study, we show that variation in moment-to-moment experienced vividness of visual imagery, within human subjects, depends on the activity of a large network of brain areas, including frontal, parietal, and visual areas. Furthermore, using a novel multivariate analysis technique, we show that the neural overlap between imagery and perception in the entire visual system correlates with experienced imagery vividness. This shows that the neural basis of imagery vividness is much more complicated than studies of individual differences seemed to suggest. Visual imagery is the ability to visualize objects that are not in our direct line of sight: something that is important for memory, spatial reasoning, and many other tasks. It is known that the better people are at visual imagery, the better they can perform these tasks. However, the neural correlates of moment-to-moment variation in visual imagery remain unclear. In this study, we show that the more the neural response during imagery is similar to the neural response during perception, the more vivid or perception-like the imagery experience is. Copyright © 2017 the authors 0270-6474/17/371367-07$15.00/0.

  20. Bilateral patching in retinal detachment: fluid mechanics and retinal "settling".

    Science.gov (United States)

    Foster, William J

    2011-07-20

    When a patient suffers a retinal detachment and surgery is delayed, it is known clinically that bilaterally patching the patient may allow the retina to partially reattach or "settle." Although this procedure has been performed since the 1860s, there is still debate as to how such a maneuver facilitates the reattachment of the retina. Finite element calculations using commercially available analysis software are used to elucidate the influence of reduction in eye movement caused by bilateral patching on the flow of subretinal fluid in a physical model of retinal detachment. It was found that by coupling fluid mechanics with structural mechanics, a physically consistent explanation of increased retinal detachment with eye movements can be found in the case of traction on the retinal hole. Large eye movements increase vitreous traction and detachment forces on the edge of the retinal hole, creating a subretinal vacuum and facilitating increased subretinal fluid. Alternative models, in which intraocular fluid flow is redirected into the subretinal space, are not consistent with these simulations. The results of these simulations explain the physical principles behind bilateral patching and provide insight that can be used clinically. In particular, as is known clinically, bilateral patching may facilitate a decrease in the height of a retinal detachment. The results described here provide a description of a physical mechanism underlying this technique. The findings of this study may aid in deciding whether to bilaterally patch patients and in counseling patients on pre- and postoperative care.

  1. Kinesthetic imagery of musical performance

    Directory of Open Access Journals (Sweden)

    Martin eLotze

    2013-06-01

    Full Text Available Musicians use different kinds of imagery. This review focuses on kinesthetic imagery, which has been shown to be an effective complement to actively playing an instrument. However, experience in actual movement performance seems to be a requirement for a recruitment of those brain areas representing movement ideation during imagery. An internal model of movement performance might be more differentiated when training has been more intense or simply performed more often. Therefore, with respect to kinesthetic imagery, these strategies are predominantly found in professional musicians. There are a few possible reasons as to why kinesthetic imagery is used in addition to active training; one example is the need for mental rehearsal of the technically most difficult passages. Training difficult passages repeatedly has the potential to induce fatigue in tendons and muscles and can ultimately result in the development of dystonia. Another reason for mental practice is that mental rehearsal of the piece helps to improve performance if the instrument is not available for actual training as is the case for professional musicians when they are travelling to various appearances. Overall, mental imagery in musicians is not necessarily specific to motor, somatosensory, auditory or visual aspects of imagery, but integrates them all. In particular, the audiomotor loop is highly important, since auditory aspects are crucial for guiding motor performance. Furthermore, slight co-movement, for instance of the fingers, usually occurs when imagining musical performance, a situation different to the laboratory condition where movement execution is strictly controlled. All these aspects result in a distinctive representation map for the mental imagery of musical performance. This review summarizes behavioral data, and findings from functional brain imaging studies of mental imagery of musical performance.

  2. Genetics Home Reference: retinitis pigmentosa

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... in known genes account for 58% of autosomal dominant retinitis pigmentosa (adRP). Adv Exp Med Biol. 2008; ...

  3. Automated detection of retinal disease.

    Science.gov (United States)

    Helmchen, Lorens A; Lehmann, Harold P; Abràmoff, Michael D

    2014-11-01

    Nearly 4 in 10 Americans with diabetes currently fail to undergo recommended annual retinal exams, resulting in tens of thousands of cases of blindness that could have been prevented. Advances in automated retinal disease detection could greatly reduce the burden of labor-intensive dilated retinal examinations by ophthalmologists and optometrists and deliver diagnostic services at lower cost. As the current availability of ophthalmologists and optometrists is inadequate to screen all patients at risk every year, automated screening systems deployed in primary care settings and even in patients' homes could fill the current gap in supply. Expanding screens to all patients at risk by switching to automated detection systems would in turn yield significantly higher rates of detecting and treating diabetic retinopathy per dilated retinal examination. Fewer diabetic patients would develop complications such as blindness, while ophthalmologists could focus on more complex cases.

  4. Advances in Retinal Optical Imaging

    Directory of Open Access Journals (Sweden)

    Yanxiu Li

    2018-04-01

    Full Text Available Retinal imaging has undergone a revolution in the past 50 years to allow for better understanding of the eye in health and disease. Significant improvements have occurred both in hardware such as lasers and optics in addition to software image analysis. Optical imaging modalities include optical coherence tomography (OCT, OCT angiography (OCTA, photoacoustic microscopy (PAM, scanning laser ophthalmoscopy (SLO, adaptive optics (AO, fundus autofluorescence (FAF, and molecular imaging (MI. These imaging modalities have enabled improved visualization of retinal pathophysiology and have had a substantial impact on basic and translational medical research. These improvements in technology have translated into early disease detection, more accurate diagnosis, and improved management of numerous chorioretinal diseases. This article summarizes recent advances and applications of retinal optical imaging techniques, discusses current clinical challenges, and predicts future directions in retinal optical imaging.

  5. Prophylactic treatment of retinal breaks

    DEFF Research Database (Denmark)

    Blindbæk, Søren Leer; Grauslund, Jakob

    2015-01-01

    Prophylactic treatment of retinal breaks has been examined in several studies and reviews, but so far, no studies have successfully applied a systematic approach. In the present systematic review, we examined the need of follow-up after posterior vitreous detachment (PVD) - diagnosed by slit...... published before 2012. Four levels of screening identified 13 studies suitable for inclusion in this systematic review. No meta-analysis was conducted as no data suitable for statistical analysis were identified. In total, the initial examination after symptomatic PVD identified 85-95% of subsequent retinal......-47% of cases, respectively. The cumulated incidence of RRD despite prophylactic treatment was 2.1-8.8%. The findings in this review suggest that follow-up after symptomatic PVD is only necessary in cases of incomplete retinal examination at presentation. Prophylactic treatment of symptomatic retinal breaks...

  6. Imagery mismatch negativity in musicians.

    Science.gov (United States)

    Herholz, Sibylle C; Lappe, Claudia; Knief, Arne; Pantev, Christo

    2009-07-01

    The present study investigated musical imagery in musicians and nonmusicians by means of magnetoencephalography (MEG). We used a new paradigm in which subjects had to continue familiar melodies in their mind and then judged if a further presented tone was a correct continuation of the melody. Incorrect tones elicited an imagery mismatch negativity (iMMN) in musicians but not in nonmusicians. This finding suggests that the MMN component can be based on an imagined instead of a sensory memory trace and that imagery of music is modulated by musical expertise.

  7. Concentric retinitis pigmentosa: clinicopathologic correlations.

    Science.gov (United States)

    Milam, A H; De Castro, E B; Smith, J E; Tang, W X; John, S K; Gorin, M B; Stone, E M; Aguirre, G D; Jacobson, S G

    2001-10-01

    Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective

  8. Unilateral retinitis pigmentosa sine pigmento.

    Science.gov (United States)

    Pearlman, J T; Saxton, J; Hoffman, G

    1976-05-01

    A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento.

  9. Light and inherited retinal degeneration

    OpenAIRE

    Paskowitz, D M; LaVail, M M; Duncan, J L

    2006-01-01

    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  10. Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis).

    Science.gov (United States)

    van Kuijk, Frederik J G M; McPherson, Scott W; Roehrich, Heidi

    2017-08-01

    Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen. Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology. Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months. Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD.

  11. Anti-apoptotic effects of Curcuma longa L. extract and its curcuminoids against blue light-induced cytotoxicity in A2E-laden human retinal pigment epithelial cells.

    Science.gov (United States)

    Park, Sang-Il; Lee, Eun Hye; Kim, So Ra; Jang, Young Pyo

    2017-03-01

    The purpose of the study was to investigate the protective effect of the Curcuma longa L. extract (CLE) and its curcuminoids against blue light-induced cytotoxicity in human retinal pigment epithelial (RPE) cells laded with A2E. A2E has been concerned in age-related macular degeneration (AMD). To perform this study, A2E-accumulated ARPE-19 cells were exposed to blue light to induce cytotoxicity. The cytotoxicity and apoptotic gene expression levels were evaluated using a lactate dehydrogenase (LDH) assay and real-time PCR analysis, respectively. Curcuma longa L. extract was found to exert a protective effect in a dose-dependent manner. At a concentration of 15 μm, curcumin, demethoxycurcumin and bisdemethoxycurcumin exerted significant protective effects against blue light-induced cytotoxicity. Treatment with CLE and curcuminoids meaningfully reduced the mRNA levels of c-Abl and p53, which was known to be augmented in apoptotic RPE cells. Demethoxycurcumin and bisdemethoxycurcumin were found to inhibit p38 expression, which is increased in blue light-irradiated A2E-accumulated RPE cells. Curcuma longa L. extract and its curcuminoids provided significant protection against photooxidative damage and apoptosis in the RPE cells. Our results suggest that curcuminoids may show potential in the treatment of AMD. © 2017 Royal Pharmaceutical Society.

  12. Improvement of retinal blood vessel detection using morphological component analysis.

    Science.gov (United States)

    Imani, Elaheh; Javidi, Malihe; Pourreza, Hamid-Reza

    2015-03-01

    Detection and quantitative measurement of variations in the retinal blood vessels can help diagnose several diseases including diabetic retinopathy. Intrinsic characteristics of abnormal retinal images make blood vessel detection difficult. The major problem with traditional vessel segmentation algorithms is producing false positive vessels in the presence of diabetic retinopathy lesions. To overcome this problem, a novel scheme for extracting retinal blood vessels based on morphological component analysis (MCA) algorithm is presented in this paper. MCA was developed based on sparse representation of signals. This algorithm assumes that each signal is a linear combination of several morphologically distinct components. In the proposed method, the MCA algorithm with appropriate transforms is adopted to separate vessels and lesions from each other. Afterwards, the Morlet Wavelet Transform is applied to enhance the retinal vessels. The final vessel map is obtained by adaptive thresholding. The performance of the proposed method is measured on the publicly available DRIVE and STARE datasets and compared with several state-of-the-art methods. An accuracy of 0.9523 and 0.9590 has been respectively achieved on the DRIVE and STARE datasets, which are not only greater than most methods, but are also superior to the second human observer's performance. The results show that the proposed method can achieve improved detection in abnormal retinal images and decrease false positive vessels in pathological regions compared to other methods. Also, the robustness of the method in the presence of noise is shown via experimental result. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Müller stem cell dependent retinal regeneration.

    Science.gov (United States)

    Chohan, Annu; Singh, Usha; Kumar, Atul; Kaur, Jasbir

    2017-01-01

    Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas. Here, we review the current status of retinal regeneration of the human eye by Müller stem cells. This review elucidates the current status of retinal regeneration by Müller stem cells, along with major retinal degenerative diseases where these stem cells play regenerative role in retinal repair and replacement. Copyright © 2016. Published by Elsevier B.V.

  14. Therapeutic avenues for hereditary forms of retinal blindness.

    Science.gov (United States)

    Kannabiran, Chitra; Mariappan, Indumathi

    2018-03-01

    Hereditary retinal diseases, known as retinal degenerations or dystrophies, are a large group of inherited eye disorders resulting in irreversible visual loss and blindness. They develop due to mutations in one or more genes that lead to the death of the retinal photoreceptor cells. Till date, mutations in over 200 genes are known to be associated with all different forms of retinal disorders. The enormous genetic heterogeneity of this group of diseases has posedmany challenges in understanding the mechanisms of disease and in developing suitable therapies. Therapeutic avenues that are being investigated for these disorders include gene therapy to replace the defective gene, treatment with neurotrophic factors to stimulate the growth of photoreceptors, cell replacement therapy, and prosthetic devices that can capture light and transmit electrical signals through retinal neurons to the brain. Several of these are in process of human trials in patients, and have shown safety and efficacy of the treatment. A combination of approaches that involve both gene replacement and cell replacement may be required for optimum benefit.

  15. Live-cell imaging: new avenues to investigate retinal regeneration

    Directory of Open Access Journals (Sweden)

    Manuela Lahne

    2017-01-01

    Full Text Available Sensing and responding to our environment requires functional neurons that act in concert. Neuronal cell loss resulting from degenerative diseases cannot be replaced in humans, causing a functional impairment to integrate and/or respond to sensory cues. In contrast, zebrafish (Danio rerio possess an endogenous capacity to regenerate lost neurons. Here, we will focus on the processes that lead to neuronal regeneration in the zebrafish retina. Dying retinal neurons release a damage signal, tumor necrosis factor α, which induces the resident radial glia, the Müller glia, to reprogram and re-enter the cell cycle. The Müller glia divide asymmetrically to produce a Müller glia that exits the cell cycle and a neuronal progenitor cell. The arising neuronal progenitor cells undergo several rounds of cell divisions before they migrate to the site of damage to differentiate into the neuronal cell types that were lost. Molecular and immunohistochemical studies have predominantly provided insight into the mechanisms that regulate retinal regeneration. However, many processes during retinal regeneration are dynamic and require live-cell imaging to fully discern the underlying mechanisms. Recently, a multiphoton imaging approach of adult zebrafish retinal cultures was developed. We will discuss the use of live-cell imaging, the currently available tools and those that need to be developed to advance our knowledge on major open questions in the field of retinal regeneration.

  16. APFO Historical Availability of Imagery

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — The APFO Historical Availability ArcGIS Online web map provides an easy to use reference of what historical imagery is available by county from the Aerial...

  17. New percepts via mental imagery?

    Directory of Open Access Journals (Sweden)

    Fred Walter Mast

    2012-10-01

    Full Text Available We are able to extract detailed information from mental images that we were not explicitly aware of during encoding. For example, we can discover a new figure when we rotate a previously seen image in our mind. However, such discoveries are not really new but just new interpretations. In two recent publications, we have shown that mental imagery can lead to perceptual learning (Tartaglia et al., 2009, 2012. Observers imagined the central line of a bisection stimulus for thousands of trials. This training enabled observers to perceive bisection offsets that were invisible before training. Hence, it seems that perceptual learning via mental imagery leads to new percepts. We will argue, however, that these new percepts can occur only within known models. In this sense, perceptual learning via mental imagery exceeds new discoveries in mental images. Still, the effects of mental imagery on perceptual learning are limited. Only perception can lead to really new perceptual experience.

  18. Image Segmentation of Hyperspectral Imagery

    National Research Council Canada - National Science Library

    Wellman, Mark

    2003-01-01

    .... Army tactical applications. An important tactical application of infrared (IR) hyperspectral imagery is the detection of low-contrast targets, including those targets that may employ camouflage, concealment, and deception (CCD) techniques 1, 2...

  19. Establishing an experimental rat model of photodynamically-induced retinal vein occlusion using erythrosin B

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2014-04-01

    Full Text Available AIM:To develop a reliable, reproducible rat model of retinal vein occlusion (RVO with a novel photosensitizer (erythrosin B and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia. Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h, and 1, 4, 7, 14, and 21d after irradiation. Tissue slices were evaluated histopathologically. Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count. Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups, blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour. The retinal detachment rate was 100% at 3h and developed into bullous retinal detachment within 24h. Retinal hemorrhages were not observed until 24h. Clearance of the occluded veins at 7d was observed by fluorescein angiography. Disease manifestation in the central RVO eyes was more severe than in the branch RVO group. A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d, whereas moderate changes occurred in the branch RVO group.CONCLUSION: Rat RVO created by photochemically-induced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO. However, considering the 100% rate of retinal detachment, this animal model is more suitable for studying RVO with chronic retinal detachment.

  20. Segmentation of retinal blood vessels for detection of diabetic retinopathy: A review

    Directory of Open Access Journals (Sweden)

    Rezty Amalia Aras

    2016-05-01

    Full Text Available Diabetic detinopathy (DR is effect of diabetes mellitus to the human vision that is the major cause of blindness. Early diagnosis of DR is an important requirement in diabetes treatment. Retinal fundus image is commonly used to observe the diabetic retinopathy symptoms. It can present retinal features such as blood vessel and also capture the pathologies which may lead to DR. Blood vessel is one of retinal features which can show the retina pathologies. It can be extracted from retinal image by image processing with following stages: pre-processing, segmentation, and post-processing. This paper contains a review of public retinal image dataset and several methods from various conducted researches. All discussed methods are applicable to each researcher cases. There is no further analysis to conclude the best method which can be used for general cases. However, we suggest morphological and multiscale method that gives the best accuracy in segmentation.

  1. Determination of retinal surface area.

    Science.gov (United States)

    Nagra, Manbir; Gilmartin, Bernard; Thai, Ngoc Jade; Logan, Nicola S

    2017-09-01

    Previous attempts at determining retinal surface area and surface area of the whole eye have been based upon mathematical calculations derived from retinal photographs, schematic eyes and retinal biopsies of donor eyes. 3-dimensional (3-D) ocular magnetic resonance imaging (MRI) allows a more direct measurement, it can be used to image the eye in vivo, and there is no risk of tissue shrinkage. The primary purpose of this study is to compare, using T2-weighted 3D MRI, retinal surface areas for superior-temporal (ST), inferior-temporal (IT), superior-nasal (SN) and inferior-nasal (IN) retinal quadrants. An ancillary aim is to examine whether inter-quadrant variations in area are concordant with reported inter-quadrant patterns of susceptibility to retinal breaks associated with posterior vitreous detachment (PVD). Seventy-three adult participants presenting without retinal pathology (mean age 26.25 ± 6.06 years) were scanned using a Siemens 3-Tesla MRI scanner to provide T2-weighted MR images that demarcate fluid-filled internal structures for the whole eye and provide high-contrast delineation of the vitreous-retina interface. Integrated MRI software generated total internal ocular surface area (TSA). The second nodal point was used to demarcate the origin of the peripheral retina in order to calculate total retinal surface area (RSA) and quadrant retinal surface areas (QRSA) for ST, IT, SN, and IN quadrants. Mean spherical error (MSE) was -2.50 ± 4.03D and mean axial length (AL) 24.51 ± 1.57 mm. Mean TSA and RSA for the RE were 2058 ± 189 and 1363 ± 160 mm 2 , respectively. Repeated measures anova for QRSA data indicated a significant difference within-quadrants (P area/mm increase in AL. Although the differences between QRSAs are relatively small, there was evidence of concordance with reported inter-quadrant patterns of susceptibility to retinal breaks associated with PVD. The data allow AL to be converted to QRSAs, which will assist further

  2. Retinal pigmentary changes in chronic uveitis mimicking retinitis pigmentosa.

    Science.gov (United States)

    Sevgi, D Damla; Davoudi, Samaneh; Comander, Jason; Sobrin, Lucia

    2017-09-01

    To present retinal pigmentary changes mimicking retinitis pigmentosa (RP) as a finding of advanced uveitis. We retrospectively reviewed charts of patients without a family history of inherited retinal degenerations who presented with retinal pigment changes and signs of past or present intraocular inflammation. Comprehensive eye examination including best-corrected visual acuity, slit-lamp examination and dilated fundus examination was performed on all patients in addition to color fundus photography, optical coherence tomography, fluorescein angiography (FA), and full-field electroretinogram testing. We identified five patients with ages ranging from 33 to 66 years, who presented with RP-like retinal pigmentary changes which were eventually attributed to longstanding uveitis. The changes were bilateral in three cases and unilateral in two cases. Four of five cases presented with active inflammation, and the remaining case showed evidence of active intraocular inflammation during follow-up. This study highlights the overlapping features of advanced uveitis and RP including the extensive pigmentary changes. Careful review of possible past uveitis history, detailed examination of signs of past or present inflammation and ancillary testing, with FA often being most helpful, are required for the correct diagnosis. This is important, because intervention can prevent further damage if the cause of the pigmentary changes is destructive inflammation.

  3. The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2 activation

    Directory of Open Access Journals (Sweden)

    Xiaobin Liu

    2016-08-01

    Full Text Available Oxidative stress-induced retinal pigment epithelial (RPE cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD. Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200 μM H2O2 for 6 h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI double staining and Hoechst 33342 fluorescent staining. Reduced (GSH and oxidized glutathione (GSSG were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100 nM of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.

  4. Pharmacotherapy of retinal disease with visual cycle modulators.

    Science.gov (United States)

    Hussain, Rehan M; Gregori, Ninel Z; Ciulla, Thomas A; Lam, Byron L

    2018-04-01

    Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies. Expert opinion: Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.

  5. Retinal detachment in paediatric patients

    International Nuclear Information System (INIS)

    Zafar, S. N.; Qureshi, N.; Azad, N.; Khan, A.

    2013-01-01

    Objective: To assess the causes of retinal detachment in children and the various operative procedures requiring vitreoretinal surgical intervention for the same. Study Design: Case series. Place and Duration of Study: Department of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, from January 2006 to May 2009. Methodology: A total of 281 eyes of 258 patients, (aged 0 - 18 years) who underwent vitreo-retinal surgical intervention for retinal detachment were included. Surgical log was searched for the type of retinal detachment and its causes. Frequencies of various interventions done in these patients viz. vitrectomy, scleral buckle, use of tamponading agents, laser photocoagulation and cryotherapy were noted. Results were described as descriptive statistics. Results: Myopia was the cause in 62 (22.1%) and trauma in 51 (18.1%) of the eyes. Total retinal detachment (RD) was treated in 94 (33.5%) eyes, sub total RD in 36 (12.8%), recurrent RD in 32 (11.4%), giant retinal tear in 28 (10%), tractional RD in 15 (5.3%) and exudative RD in 2 (0.7%). Prophylactic laser or cryotherapy was applied in 74 (26.3%) of the eyes. Pars plana vitrectomy (PPV) was carried out in 159 (56.6%) eyes while scleral buckle procedure was done in 129 (45.9%) eyes. Silicon oil was used in 149 (53%), perfluorocarbon liquid in 32 (11.4%) and gas tamponade in 20 (7.1%) eyes. Conclusion: The most common cause of retinal detachment in paediatric patients was myopia, followed by trauma. Total RD was more common as compared to the other types. The most common procedure adopted was pars plana vitrectomy followed by scleral buckle procedure. (author)

  6. Extraction of retinal tacks from subjects implanted with an epiretinal visual prosthesis.

    Science.gov (United States)

    de Juan, Eugene; Spencer, Rand; Barale, Pierre-Olivier; da Cruz, Lyndon; Neysmith, Jordan

    2013-10-01

    Retinal tacks, first developed for the treatment of complex retinal detachments, have more recently been used for the fixation of epiretinal electrode arrays as part of implanted visual prostheses. Here, we report on the clinical experience of extracting four such tacks after chronic implantation. The ability to safely extract retinal tacks ensures that epiretinal devices can be repositioned or removed if necessary. Custom-built, titanium alloy retinal tacks were mechanically removed from the posterior coats after prolonged implantation (up to 19 months). The resulting wound was characterized by clinical evaluation, fundus photography, and fluorescein angiography while being monitored for stability over time. The wounds were also compared to earlier published reports of the healing response around retinal tacks in human subjects. Tack extraction was accomplished successfully, without complication, in all four subjects. The wound site was readily identified by pale scar tissue. No change in the wound size or appearance was noted over many months of post-operative observation (up to 22 months after explant). No adverse effects on overall ocular health were detected. Extraction of retinal tacks from subjects implanted with epiretinal prostheses can be performed without significant complication. The long-term healing response appears to be stable and localized in eyes afflicted with retinitis pigmentosa or choroideremia. There was also minimal, if any, impact on the local circulatory system. These cases suggest that the use of retinal tacks for anchoring epiretinal visual prostheses does not preclude safe repositioning or removal of the device more than a year after implant.

  7. Col4a1 mutations cause progressive retinal neovascular defects and retinopathy.

    Science.gov (United States)

    Alavi, Marcel V; Mao, Mao; Pawlikowski, Bradley T; Kvezereli, Manana; Duncan, Jacque L; Libby, Richard T; John, Simon W M; Gould, Douglas B

    2016-01-27

    Mutations in collagen, type IV, alpha 1 (COL4A1), a major component of basement membranes, cause multisystem disorders in humans and mice. In the eye, these include anterior segment dysgenesis, optic nerve hypoplasia and retinal vascular tortuosity. Here we investigate the retinal pathology in mice carrying dominant-negative Col4a1 mutations. To this end, we examined retinas longitudinally in vivo using fluorescein angiography, funduscopy and optical coherence tomography. We assessed retinal function by electroretinography and studied the retinal ultrastructural pathology. Retinal examinations revealed serous chorioretinopathy, retinal hemorrhages, fibrosis or signs of pathogenic angiogenesis with chorioretinal anastomosis in up to approximately 90% of Col4a1 mutant eyes depending on age and the specific mutation. To identify the cell-type responsible for pathogenesis we generated a conditional Col4a1 mutation and determined that primary vascular defects underlie Col4a1-associated retinopathy. We also found focal activation of Müller cells and increased expression of pro-angiogenic factors in retinas from Col4a1(+/Δex41)mice. Together, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk of retinal hemorrhages and that retinal examinations may be useful for identifying patients with COL4A1 and COL4A2 mutations who are also at elevated risk of hemorrhagic strokes.

  8. Retinal vascular oximetry during ranibizumab treatment of central retinal vein occlusion

    DEFF Research Database (Denmark)

    Traustason, Sindri; la Cour, Morten; Larsen, Michael

    2014-01-01

    PURPOSE: To investigate the effect of intravitreal injections of the vascular endothelial growth factor inhibitor ranibizumab on retinal oxygenation in patients with central retinal vein occlusion (CRVO). METHODS: Retinal oxygen saturation in patients with CRVO was analysed using the Oxymap Retin...

  9. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

    Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

  10. Regulating with imagery and the complexity of basic emotions. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    Science.gov (United States)

    Meyer, Marcel; Kuchinke, Lars

    2015-06-01

    Literature, music and the arts have long attested to the complexity of human emotions. Hitherto, psychological and biological theories of emotions have largely neglected this rich heritage. In their review Koelsch and colleagues [1] have embarked upon the pioneering endeavour of integrating the diverse perspectives in emotion research. Noting that the focus of prior neurobiological theories relies mainly on animal studies, the authors sought to complement this body of research with a model of complex ("moral") emotions in humans (henceforth: complex emotions). According to this novel framework, there are four main interacting affective centres in the brain. Each centre is associated with a dominant affective function, such as ascending activation (brainstem), pain/pleasure (diencephalon), attachment-related affects (hippocampus) or moral emotions and unconscious cognitive appraisal (orbitofrontal cortex). Furthermore, language is ascribed a key role in (a) the communication of subjective feeling (reconfiguration) and (b) in the conscious regulation of emotions (by means of logic and rational thought).

  11. Mitochondrial dysfunction underlying outer retinal diseases

    DEFF Research Database (Denmark)

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali

    2017-01-01

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer...

  12. Toward interactive search in remote sensing imagery

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Reid B [Los Alamos National Laboratory; Hush, Do [Los Alamos National Laboratory; Harvey, Neal [Los Alamos National Laboratory; Theile, James [Los Alamos National Laboratory

    2010-01-01

    To move from data to information in almost all science and defense applications requires a human-in-the-loop to validate information products, resolve inconsistencies, and account for incomplete and potentially deceptive sources of information. This is a key motivation for visual analytics which aims to develop techniques that complement and empower human users. By contrast, the vast majority of algorithms developed in machine learning aim to replace human users in data exploitation. In this paper we describe a recently introduced machine learning problem, called rare category detection, which may be a better match to visual analytic environments. We describe a new design criteria for this problem, and present comparisons to existing techniques with both synthetic and real-world datasets. We conclude by describing an application in broad-area search of remote sensing imagery.

  13. Toward interactive search in remote sensing imagery

    Science.gov (United States)

    Porter, Reid; Hush, Don; Harvey, Neal; Theiler, James

    2010-04-01

    To move from data to information in almost all science and defense applications requires a human-in-the-loop to validate information products, resolve inconsistencies, and account for incomplete and potentially deceptive sources of information. This is a key motivation for visual analytics which aims to develop techniques that complement and empower human users. By contrast, the vast majority of algorithms developed in machine learning aim to replace human users in data exploitation. In this paper we describe a recently introduced machine learning problem, called rare category detection, which may be a better match to visual analytic environments. We describe a new design criteria for this problem, and present comparisons to existing techniques with both synthetic and real-world datasets. We conclude by describing an application in broad-area search of remote sensing imagery.

  14. Patterning of pain and power with guided imagery.

    Science.gov (United States)

    Lewandowski, Wendy A

    2004-07-01

    Using Martha Rogers' science of unitary human beings, changes in pain and power among 42 patients were examined in relation to the use of a guided imagery modality. Participants were randomly assigned to treatment and control groups and repeated measures MANCOVA was used to detect differences in pain and power over a 4-day period of time. The treatment group's pain decreased during the last 2 days of the study. No differences in power emerged. Guided imagery appeared to have potential as a useful nursing modality for chronic pain sufferers.

  15. Retinal detachment in black South Africans

    African Journals Online (AJOL)

    low incidence of retinal detachment in black patients is not known. ... a retinal break. Predisposing factors include peripheral retinal degenerations, myopia, aphakia and trauma. Delay in presentation increases the difficulty in achieving adequate surgical ... On examination, note was taken of the visual acuity in both eyes, the ...

  16. Transcorneal Electrical Stimulation Therapy for Retinal Disease

    Science.gov (United States)

    2012-05-03

    Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

  17. Diabetes and Retinal Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    2014-01-01

    Full Text Available Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR. We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

  18. Optical modulation of transgene expression in retinal pigment epithelium

    Science.gov (United States)

    Palanker, D.; Lavinsky, D.; Chalberg, T.; Mandel, Y.; Huie, P.; Dalal, R.; Marmor, M.

    2013-03-01

    Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a "biofactory" that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

  19. Gene Therapy in a Large Animal Model of PDE6A-Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Freya M. Mowat

    2017-06-01

    Full Text Available Despite mutations in the rod phosphodiesterase 6-alpha (PDE6A gene being well-recognized as a cause of human retinitis pigmentosa, no definitive treatments have been developed to treat this blinding disease. We performed a trial of retinal gene augmentation in the Pde6a mutant dog using Pde6a delivery by capsid-mutant adeno-associated virus serotype 8, previously shown to have a rapid onset of transgene expression in the canine retina. Subretinal injections were performed in 10 dogs at 29–44 days of age, and electroretinography and vision testing were performed to assess functional outcome. Retinal structure was assessed using color fundus photography, spectral domain optical coherence tomography, and histology. Immunohistochemistry was performed to examine transgene expression and expression of other retinal genes. Treatment resulted in improvement in dim light vision and evidence of rod function on electroretinographic examination. Photoreceptor layer thickness in the treated area was preserved compared with the contralateral control vector treated or uninjected eye. Improved rod and cone photoreceptor survival, rhodopsin localization, cyclic GMP levels and bipolar cell dendrite distribution was observed in treated areas. Some adverse effects including foci of retinal separation, foci of retinal degeneration and rosette formation were identified in both AAV-Pde6a and control vector injected regions. This is the first description of successful gene augmentation for Pde6a retinitis pigmentosa in a large animal model. Further studies will be necessary to optimize visual outcomes and minimize complications before translation to human studies.

  20. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Science.gov (United States)

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  1. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Shobi Veleri

    2015-02-01

    Full Text Available Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

  2. Enhancing voluntary imitation through attention and motor imagery.

    Science.gov (United States)

    Bek, Judith; Poliakoff, Ellen; Marshall, Hannah; Trueman, Sophie; Gowen, Emma

    2016-07-01

    Action observation activates brain areas involved in performing the same action and has been shown to increase motor learning, with potential implications for neurorehabilitation. Recent work indicates that the effects of action observation on movement can be increased by motor imagery or by directing attention to observed actions. In voluntary imitation, activation of the motor system during action observation is already increased. We therefore explored whether imitation could be further enhanced by imagery or attention. Healthy participants observed and then immediately imitated videos of human hand movement sequences, while movement kinematics were recorded. Two blocks of trials were completed, and after the first block participants were instructed to imagine performing the observed movement (Imagery group, N = 18) or attend closely to the characteristics of the movement (Attention group, N = 15), or received no further instructions (Control group, N = 17). Kinematics of the imitated movements were modulated by instructions, with both Imagery and Attention groups being closer in duration, peak velocity and amplitude to the observed model compared with controls. These findings show that both attention and motor imagery can increase the accuracy of imitation and have implications for motor learning and rehabilitation. Future work is required to understand the mechanisms by which these two strategies influence imitation accuracy.

  3. Retinal image quality during accommodation.

    Science.gov (United States)

    López-Gil, Norberto; Martin, Jesson; Liu, Tao; Bradley, Arthur; Díaz-Muñoz, David; Thibos, Larry N

    2013-07-01

    We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Subjects viewed a monochromatic (552 nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye's higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced visual function may be a useful

  4. A mathematical model for describing the retinal nerve fiber bundle trajectories in the human eye: average course, variability, and influence of refraction, optic disc size and optic disc position.

    Science.gov (United States)

    Jansonius, Nomdo M; Schiefer, Julia; Nevalainen, Jukka; Paetzold, Jens; Schiefer, Ulrich

    2012-12-01

    Previously we developed a mathematical model for describing the retinal nerve fiber bundle trajectories in the superior-temporal and inferior-temporal regions of the human retina, based on traced trajectories extracted from fundus photographs. Aims of the current study were to (i) validate the existing model, (ii) expand the model to the entire retina and (iii) determine the influence of refraction, optic disc size and optic disc position on the trajectories. A new set of fundus photographs was collected comprising 28 eyes of 28 subjects. From these 28 photographs, 625 trajectories were extracted. Trajectories in the temporal region of the retina were compared to the existing model. In this region, 347 of 399 trajectories (87%) were within the 95% central range of the existing model. The model was extended to the nasal region. With this extension, the model can now be applied to the entire retina that corresponds to the visual field as tested with standard automated perimetry (up to approximately 30° eccentricity). There was an asymmetry between the superior and inferior hemifields and a considerable location-specific inter-subject variability. In the nasal region, we found two "singularities", located roughly at the one and five o'clock positions for the right optic disc. Here, trajectories from relatively widespread areas of the retina converge. Associations between individual deviations from the model and refraction, optic disc size and optic disc position were studied with multiple linear regression. Refraction (P = 0.021) and possibly optic disc inclination (P = 0.09) influenced the trajectories in the superior-temporal region. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance

    Directory of Open Access Journals (Sweden)

    Jeffery Glen

    2008-05-01

    Full Text Available Abstract Background The transcription factor Pax6 is expressed by many cell types in the developing eye. Eyes do not form in homozygous loss-of-function mouse mutants (Pax6Sey/Sey and are abnormally small in Pax6Sey/+ mutants. Eyes are also abnormally small in PAX77 mice expressing multiple copies of human PAX6 in addition to endogenous Pax6; protein sequences are identical in the two species. The developmental events that lead to microphthalmia in PAX77 mice are not well-characterised, so it is not clear whether over- and under-expression of Pax6/PAX6 cause microphthalmia through similar mechanisms. Here, we examined the consequences of over-expression for the eye and its axonal connections. Results Eyes form in PAX77+/+ embryos but subsequently degenerate. At E12.5, we found no abnormalities in ocular morphology, retinal cell cycle parameters and the incidence of retinal cell death. From E14.5 on, we observed malformations of the optic disc. From E16.5 into postnatal life there is progressively more severe retinal dysplasia and microphthalmia. Analyses of patterns of gene expression indicated that PAX77+/+ retinae produce a normal range of cell types, including retinal ganglion cells (RGCs. At E14.5 and E16.5, quantitative RT-PCR with probes for a range of molecules associated with retinal development showed only one significant change: a slight reduction in levels of mRNA encoding the secreted morphogen Shh at E16.5. At E16.5, tract-tracing with carbocyanine dyes in PAX77+/+ embryos revealed errors in intraretinal navigation by RGC axons, a decrease in the number of RGC axons reaching the thalamus and an increase in the proportion of ipsilateral projections among those RGC axons that do reach the thalamus. A survey of embryos with different Pax6/PAX6 gene dosage (Pax6Sey/+, Pax6+/+, PAX77+ and PAX77+/+ showed that (1 the total number of RGC axons projected by the retina and (2 the proportions that are sorted into the ipsilateral and

  6. Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model.

    Science.gov (United States)

    Jeng, Yung-Yue; Lin, Nien-Ting; Chang, Pen-Heng; Huang, Yuan-Ping; Pang, Victor Fei; Liu, Chen-Hsuan; Lin, Chung-Tien

    2007-03-01

    Retinal ischemia is a common cause of visual impairment for humans and animals. Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic injury were investigated using a rat model. Retinal ganglion cells (RGCs) were retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the superior collicoli of test Sprague-Dawley rats. High intraocular pressure and retinal ischemia were induced seven days subsequent to such FG labeling. A dose of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at two time points, namely 30 min prior to the induction of retinal ischemia and 1 h subsequent to the cessation of the procedure inducing retinal ischemia. The test-rat retinas were collected seven days subsequent to the induction of retinal ischemia, and densities of surviving RGCs were estimated by counting FG-labeled RGCs within the retina. Histological analysis revealed that ischemic injury caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA-treated groups, almost 100% of the RGCs were preserved by a pre-ischemia treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly reduced the level of ischemia-associated loss of thickness of the total retina, especially the inner retina, and the inner plexiform layer of retina. Besides, PBA treatment significantly reduced the ischemia-induced loss of cells in the ganglion-cell layer of the retina. Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction.

  7. AgSat Imagery Collection Footprints

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — The AgSat Imagery Collection Footprints map shows the imagery footprints which have been collected under the USDA satellite blanket purchase agreement. Click on a...

  8. Concepts are not represented by conscious imagery

    NARCIS (Netherlands)

    D. Pecher (Diane); S. van Dantzig (Saskia); H.N.J. Schifferstien (Hendrik)

    2009-01-01

    textabstractAccording to theories of grounded cognition, conceptual representation and perception share processing mechanisms. We investigated whether this overlap is due to conscious perceptual imagery. Participants filled out questionnaires to assess the vividness of their imagery (Questionnaire

  9. Guidance of retinal axons in mammals.

    Science.gov (United States)

    Herrera, Eloísa; Erskine, Lynda; Morenilla-Palao, Cruz

    2017-11-26

    In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Transplantation of rat embryonic stem cell-derived retinal progenitor cells preserves the retinal structure and function in rat retinal degeneration.

    Science.gov (United States)

    Qu, Zepeng; Guan, Yuan; Cui, Lu; Song, Jian; Gu, Junjie; Zhao, Hanzhi; Xu, Lei; Lu, Lixia; Jin, Ying; Xu, Guo-Tong

    2015-11-09

    rESCs to glia enriched RPCs and retinal neuron enriched RPCs in vitro. The retinal neuron enriched rESC-RPC2 protected the structure and function of retina in rats with genetic retinal degeneration and could be a candidate cell source for treating some degenerative retinal diseases in human trials.

  11. Risk factor profile in retinal detachment

    Directory of Open Access Journals (Sweden)

    Azad Raj

    1988-01-01

    Full Text Available 150 cases of retinal detachment comprising 50 patients each of bilateral retinal detachment, unilateral retinal detachment without any retinal lesions in the fellow eve and unilateral retinal detachment with retinal lesions in the fellow eye were studied and the various associated risk factors were statistically analysed. The findings are discussed in relation to their aetiological and prognostic significance in the different types of retinal detachment. Based on these observations certain guidelines are offered which may be of value in decision making, in prophylactic detachment surgery. Tractional breaks in the superior temporal quadrant especially when symptomatic. mandate prophylactic treatment. Urgency is enhanced it′ the patient is aphakic. Associated myopia adds to the urgency. The higher incidence of initial right e′ e involvement in all groups suggests a vascular original possibly ischaemic.

  12. Retinitis Pigmentosa and Education Issues

    Science.gov (United States)

    Brown, Thomas J.

    2005-01-01

    Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…

  13. [Surgical managment of retinal detachment].

    Science.gov (United States)

    Haritoglou, C; Wolf, A

    2015-05-01

    The detachment of the neurosensory retina from the underlying retinal pigment epithelium can be related to breaks of the retina allowing vitreous fluid to gain access to the subretinal space, to exudative changes of the choroid such as tumours or inflammatory diseases or to excessive tractional forces exerted by interactions of the collagenous vitreous and the retina. Tractional retinal detachment is usually treated by vitrectomy and exudative detachment can be addressed by treatment of the underlying condition in many cases. In rhegmatogenous retinal detachment two different surgical procedures, vitrectomy and scleral buckling, can be applied for functional and anatomic rehabilitation of our patients. The choice of the surgical procedure is not really standardised and often depends on the experience of the surgeon and other more ocular factors including lens status, the number of retinal breaks, the extent of the detachment and the amount of preexisting PVR. Using both techniques, anatomic success rates of over 90 % can be achieved. Especially in young phakic patients scleral buckling offers the true advantage to prevent the progression of cataract formation requiring cataract extraction and intraocular lens implantation. Therefore, scleral buckling should be considered in selected cases as an alternative surgical option in spite of the very important technical refinements in modern vitrectomy techniques. Georg Thieme Verlag KG Stuttgart · New York.

  14. Retinal imaging and image analysis

    NARCIS (Netherlands)

    Abramoff, M.D.; Garvin, Mona K.; Sonka, Milan

    2010-01-01

    Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of

  15. Agency Video, Audio and Imagery Library

    Science.gov (United States)

    Grubbs, Rodney

    2015-01-01

    The purpose of this presentation was to inform the ISS International Partners of the new NASA Agency Video, Audio and Imagery Library (AVAIL) website. AVAIL is a new resource for the public to search for and download NASA-related imagery, and is not intended to replace the current process by which the International Partners receive their Space Station imagery products.

  16. Neonatal disease environment limits the efficacy of retinal transplantation in the LCA8 mouse model

    OpenAIRE

    Cho, Seo-Hee; Song, Ji Yun; Shin, Jinyeon; Kim, Seonhee

    2016-01-01

    Background Mutations of Crb1 gene cause irreversible and incurable visual impairment in humans. This study aims to use an LCA8-like mouse model to identify host-mediated responses that might interfere with survival, retinal integration and differentiation of grafted cells during neonatal cell therapy. Methods Mixed retinal donor cells (1?~?2???104) isolated from neural retinas of neonatal eGFP transgenic mice were injected into the subretinal space of LCA8-like model neonatal mice. Markers of...

  17. Technical Brief: A comparison of two methods of euthanasia on retinal dopamine levels

    OpenAIRE

    Hwang, Christopher K.; Iuvone, P. Michael

    2013-01-01

    Purpose Mice are commonly used in biomedical research, and euthanasia is an important part of mouse husbandry. Approved, humane methods of euthanasia are designed to minimize the potential for pain or discomfort, but may also influence the measurement of experimental variables. Methods We compared the effects of two approved methods of mouse euthanasia on the levels of retinal dopamine. We examined the level of retinal dopamine, a commonly studied neuromodulator, following euthanasia by carbo...

  18. Visual advantage in deaf adults linked to retinal changes.

    Directory of Open Access Journals (Sweden)

    Charlotte Codina

    Full Text Available The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14 and hearing (N = 15 adults using Optical Coherence Tomography (OCT, an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.

  19. Treatment of Laser-Induced Retinal Injury and Visual Loss Using Sustained Release of Intra-Vitreal Neurotrophic Growth Factors. Addendum

    Science.gov (United States)

    2011-11-01

    phagocytosed melanine granules. Significant microglial infiltration was present in different retinal layers (arrow heads in red boxes). 2 Figure...photoreceptor density, corresponds to human macula), c) set of linear scans through inferior/non-tapetal fundus (these scans were aligned vertically...degree of retinal pigmentation affects the degree of laser damage and recovery with treatment, analogous to humans with differing eye pigmentation

  20. High-resolution satellite imagery is an important yet underutilized resource in conservation biology.

    Science.gov (United States)

    Boyle, Sarah A; Kennedy, Christina M; Torres, Julio; Colman, Karen; Pérez-Estigarribia, Pastor E; de la Sancha, Noé U

    2014-01-01

    Technological advances and increasing availability of high-resolution satellite imagery offer the potential for more accurate land cover classifications and pattern analyses, which could greatly improve the detection and quantification of land cover change for conservation. Such remotely-sensed products, however, are often expensive and difficult to acquire, which prohibits or reduces their use. We tested whether imagery of high spatial resolution (≤5 m) differs from lower-resolution imagery (≥30 m) in performance and extent of use for conservation applications. To assess performance, we classified land cover in a heterogeneous region of Interior Atlantic Forest in Paraguay, which has undergone recent and dramatic human-induced habitat loss and fragmentation. We used 4 m multispectral IKONOS and 30 m multispectral Landsat imagery and determined the extent to which resolution influenced the delineation of land cover classes and patch-level metrics. Higher-resolution imagery more accurately delineated cover classes, identified smaller patches, retained patch shape, and detected narrower, linear patches. To assess extent of use, we surveyed three conservation journals (Biological Conservation, Biotropica, Conservation Biology) and found limited application of high-resolution imagery in research, with only 26.8% of land cover studies analyzing satellite imagery, and of these studies only 10.4% used imagery ≤5 m resolution. Our results suggest that high-resolution imagery is warranted yet under-utilized in conservation research, but is needed to adequately monitor and evaluate forest loss and conversion, and to delineate potentially important stepping-stone fragments that may serve as corridors in a human-modified landscape. Greater access to low-cost, multiband, high-resolution satellite imagery would therefore greatly facilitate conservation management and decision-making.

  1. OCT as a convenient tool to assess the quality and application of organotypic retinal samples

    Science.gov (United States)

    Gater, Rachel; Khoshnaw, Nicholas; Nguyen, Dan; El Haj, Alicia J.; Yang, Ying

    2016-03-01

    Eye diseases such as macular degeneration and glaucoma have profound consequences on the quality of human life. Without treatment, these diseases can lead to loss of sight. To develop better treatments for retinal diseases, including cell therapies and drug intervention, establishment of an efficient and reproducible 3D native retinal tissue system, enabled over a prolonged culture duration, will be valuable. The retina is a complex tissue, consisting of ten layers with a different density and cellular composition to each. Uniquely, as a light transmitting tissue, retinal refraction of light differs among the layers, forming a good basis to use optical coherence tomography (OCT) in assessing the layered structure of the retina and its change during the culture and treatments. In this study, we develop a new methodology to generate retinal organotypic tissues and compare two substrates: filter paper and collagen hydrogel, to culture the organotypic tissue. Freshly slaughtered pig eyes have been obtained for use in this study. The layered morphology of intact organotypic retinal tissue cultured on two different substrates has been examined by spectral domain OCT. The viability of the tissues has been examined by live/dead fluorescence dye kit to cross validate the OCT images. For the first time, it is demonstrated that the use of a collagen hydrogel supports the viability of retinal organotypic tissue, capable of prolonged culture up to 2 weeks. OCT is a convenient tool for appraising the quality and application of organotypic retinal samples and is important in the development of current organotypic models.

  2. Real-Time Imaging of Retinal Ganglion Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Timothy E. Yap

    2018-06-01

    Full Text Available Monitoring real-time apoptosis in-vivo is an unmet need of neurodegeneration science, both in clinical and research settings. For patients, earlier diagnosis before the onset of symptoms provides a window of time in which to instigate treatment. For researchers, being able to objectively monitor the rates of underlying degenerative processes at a cellular level provides a biomarker with which to test novel therapeutics. The DARC (Detection of Apoptosing Retinal Cells project has developed a minimally invasive method using fluorescent annexin A5 to detect rates of apoptosis in retinal ganglion cells, the key pathological process in glaucoma. Numerous animal studies have used DARC to show efficacy of novel, pressure-independent treatment strategies in models of glaucoma and other conditions where retinal apoptosis is reported, including Alzheimer’s disease. This may forge exciting new links in the clinical science of treating both cognitive and visual decline. Human trials are now underway, successfully demonstrating the safety and efficacy of the technique to differentiate patients with progressive neurodegeneration from healthy individuals. We review the current perspectives on retinal ganglion cell apoptosis, the way in which this can be imaged, and the exciting advantages that these future methods hold in store.

  3. Media, Mental Imagery, and Memory.

    Science.gov (United States)

    Clark, Robert L.

    1978-01-01

    Thirty-two students at the University of Oregon were tested to determine the effects of media on mental imagery and memory. The model incorporates a dual coding hypothesis, and five single and multiple channel treatments were used. (Author/JEG)

  4. Dialectical Imagery and Postmodern Research

    Science.gov (United States)

    Davison, Kevin G.

    2006-01-01

    This article suggests utilizing dialectical imagery, as understood by German social philosopher Walter Benjamin, as an additional qualitative data analysis strategy for research into the postmodern condition. The use of images mined from research data may offer epistemological transformative possibilities that will assist in the demystification of…

  5. Illustrating and Designing Quranic Imagery

    Science.gov (United States)

    Almenoar, Lubna

    2009-01-01

    Selected verses from Abdullah Yusuf Ali's English language translation of the meaning of the Quran have been used as a literary text to teach both descriptive and figurative imagery (including similes, metaphors and symbols) to students at the undergraduate level in an Islamic institution. The technique--Illustrating and Designing for teaching…

  6. Characterization of a dehydrogenase activity responsible for oxidation of 11-cis-retinol in the retinal pigment epithelium of mice with a disrupted RDH5 gene. A model for the human hereditary disease fundus albipunctatus.

    NARCIS (Netherlands)

    Jang, G.F.; Hooser, J.P. van; Kuksa, V.; McBee, J.K.; He, Y.G.; Janssen, J.J.M.; Driessen, C.A.G.G.; Palczewski, K.

    2001-01-01

    In the vertebrate retina, the final step of visual chromophore production is the oxidation of 11-cis-retinol to 11-cis-retinal. This reaction is catalyzed by 11-cis-retinol dehydrogenases (11-cis-RDHs), prior to the chromophore rejoining with the visual pigment apo-proteins. The RDH5 gene encodes a

  7. Encoding and analyzing aerial imagery using geospatial semantic graphs

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Jean-Paul; Strip, David R.; McLendon, William Clarence,; Parekh, Ojas D.; Diegert, Carl F.; Martin, Shawn Bryan; Rintoul, Mark Daniel

    2014-02-01

    While collection capabilities have yielded an ever-increasing volume of aerial imagery, analytic techniques for identifying patterns in and extracting relevant information from this data have seriously lagged. The vast majority of imagery is never examined, due to a combination of the limited bandwidth of human analysts and limitations of existing analysis tools. In this report, we describe an alternative, novel approach to both encoding and analyzing aerial imagery, using the concept of a geospatial semantic graph. The advantages of our approach are twofold. First, intuitive templates can be easily specified in terms of the domain language in which an analyst converses. These templates can be used to automatically and efficiently search large graph databases, for specific patterns of interest. Second, unsupervised machine learning techniques can be applied to automatically identify patterns in the graph databases, exposing recurring motifs in imagery. We illustrate our approach using real-world data for Anne Arundel County, Maryland, and compare the performance of our approach to that of an expert human analyst.

  8. Matte painting in stereoscopic synthetic imagery

    Science.gov (United States)

    Eisenmann, Jonathan; Parent, Rick

    2010-02-01

    While there have been numerous studies concerning human perception in stereoscopic environments, rules of thumb for cinematography in stereoscopy have not yet been well-established. To that aim, we present experiments and results of subject testing in a stereoscopic environment, similar to that of a theater (i.e. large flat screen without head-tracking). In particular we wish to empirically identify thresholds at which different types of backgrounds, referred to in the computer animation industry as matte paintings, can be used while still maintaining the illusion of seamless perspective and depth for a particular scene and camera shot. In monoscopic synthetic imagery, any type of matte painting that maintains proper perspective lines, depth cues, and coherent lighting and textures saves in production costs while still maintaining the illusion of an alternate cinematic reality. However, in stereoscopic synthetic imagery, a 2D matte painting that worked in monoscopy may fail to provide the intended illusion of depth because the viewer has added depth information provided by stereopsis. We intend to observe two stereoscopic perceptual thresholds in this study which will provide practical guidelines indicating when to use each of three types of matte paintings. We ran subject tests in two virtual testing environments, each with varying conditions. Data were collected showing how the choices of the users matched the correct response, and the resulting perceptual threshold patterns are discussed below.

  9. The neoplasms imagery

    International Nuclear Information System (INIS)

    Giger, M.; Pilizzari, CH.

    1996-01-01

    New devices of NMR imaging and computed tomography give three-dimensional images of the human body and automatically interpret the anatomical pictures. These new techniques are useful for the detection and the treatment of neoplasms. They are explained into details. (O.M.)

  10. Screening for retinitis in children with probable systemic ...

    African Journals Online (AJOL)

    CMV retinitis may be prevented by timely diagnosis and treatment. This study aimed to .... retinitis are: 'a fulminant picture of retinal vasculitis and vascular sheathing with areas of yellow-white, full thickness, retinal necrosis producing retinal oedema associated ... and intravenous foscarnet as alternatives.[4] Although CMV- ...

  11. Zika virus infection of cellular components of the blood-retinal barriers: implications for viral associated congenital ocular disease.

    Science.gov (United States)

    Roach, Tracoyia; Alcendor, Donald J

    2017-03-03

    Ocular abnormalities present in microcephalic infants with presumed Zika virus (ZIKV) congenital disease includes focal pigment mottling of the retina, chorioretinal atrophy, optic nerve abnormalities, and lens dislocation. Target cells in the ocular compartment for ZIKV infectivity are unknown. The cellular response of ocular cells to ZIKV infection has not been described. Mechanisms for viral dissemination in the ocular compartment of ZIKV-infected infants and adults have not been reported. Here, we identify target cells for ZIKV infectivity in both the inner and outer blood-retinal barriers (IBRB and OBRB), describe the cytokine expression profile in the IBRB after ZIKV exposure, and propose a mechanism for viral dissemination in the retina. We expose primary cellular components of the IBRB including human retinal microvascular endothelial cells, retinal pericytes, and Müller cells as well as retinal pigmented epithelial cells of the OBRB to the PRVABC56 strain of ZIKV. Viral infectivity was analyzed by microscopy, immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR and qRT-PCR). Angiogenic and proinflammatory cytokines were measured by Luminex assays. We find by immunofluorescent staining using the Flavivirus 4G2 monoclonal antibody that retinal endothelial cells and pericytes of the IBRB and retinal pigmented epithelial cells of the OBRB are fully permissive for ZIKV infection but not Müller cells when compared to mock-infected controls. We confirmed ZIKV infectivity in retinal endothelial cells, retinal pericytes, and retinal pigmented epithelial cells by RT-PCR and qRT-PCR using ZIKV-specific oligonucleotide primers. Expression profiles by Luminex assays in retinal endothelial cells infected with ZIKV revealed a marginal increase in levels of beta-2 microglobulin (β2-m), granulocyte macrophage colony-stimulating factor (GMCSF), intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP

  12. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    Science.gov (United States)

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

  13. Prevalence of generalized retinal dystrophy in Denmark

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Jensen, Hanne; Bregnhøj, Jesper F

    2014-01-01

    of this study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in the Danish population. METHODS: A population-based cross-sectional study with data from the Danish Retinitis Pigmentosa Registry that comprises all patients in Denmark with generalized retinal......PURPOSE: Generalized retinal dystrophy is a frequent cause of visual impairment and blindness in younger individuals and a subject of new clinical intervention trials. Nonetheless, there are few nation-wide population-based epidemiological data of generalized retinal dystrophy. The purpose...... and chorioretinal dystrophies from the 19th century to the present. Among 3076 registered cases, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Demographic data on the Danish population were retrieved from Statistics Denmark...

  14. Automatic Vessel Segmentation on Retinal Images

    Institute of Scientific and Technical Information of China (English)

    Chun-Yuan Yu; Chia-Jen Chang; Yen-Ju Yao; Shyr-Shen Yu

    2014-01-01

    Several features of retinal vessels can be used to monitor the progression of diseases. Changes in vascular structures, for example, vessel caliber, branching angle, and tortuosity, are portents of many diseases such as diabetic retinopathy and arterial hyper-tension. This paper proposes an automatic retinal vessel segmentation method based on morphological closing and multi-scale line detection. First, an illumination correction is performed on the green band retinal image. Next, the morphological closing and subtraction processing are applied to obtain the crude retinal vessel image. Then, the multi-scale line detection is used to fine the vessel image. Finally, the binary vasculature is extracted by the Otsu algorithm. In this paper, for improving the drawbacks of multi-scale line detection, only the line detectors at 4 scales are used. The experimental results show that the accuracy is 0.939 for DRIVE (digital retinal images for vessel extraction) retinal database, which is much better than other methods.

  15. Retinal Image Preprocessing: Background and Noise Segmentation

    Directory of Open Access Journals (Sweden)

    Usman Akram

    2012-09-01

    Full Text Available Retinal images are used for the automated screening and diagnosis of diabetic retinopathy. The retinal image quality must be improved for the detection of features and abnormalities and for this purpose preprocessing of retinal images is vital. In this paper, we present a novel automated approach for preprocessing of colored retinal images. The proposed technique improves the quality of input retinal image by separating the background and noisy area from the overall image. It contains coarse segmentation and fine segmentation. Standard retinal images databases Diaretdb0, Diaretdb1, DRIVE and STARE are used to test the validation of our preprocessing technique. The experimental results show the validity of proposed preprocessing technique.

  16. [Peripheral retinal degenerations--treatment recommendations].

    Science.gov (United States)

    Joussen, A M; Kirchhof, B

    2004-10-01

    This report reviews the clinical appearance of degenerative diseases of the peripheral retina in relationship to the risk of developing a rhegmatogenous retinal detachment. We present recommendations for preventive treatment in eyes at increased risk of developing retinal detachment. Retinal degenerations are common lesions involving the peripheral retina but most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and very rarely zonular traction tufts can result in rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic treatment; however, adequate studies have not been performed to date. Most of the peripheral retinal degenerations may not require treatment except in rare, high-risk situations. According to current knowledge there is no higher incidence of secondary pucker or other side effects after laser coagulation. Therefore, generous laser indication is recommended if risk factors apply.

  17. [Prophylactic treatment of retinal detachment].

    Science.gov (United States)

    Binder, S; Riss, B

    1981-08-01

    The indications for and results of prophylactic treatment of retinal detachment during a period of five years are reported and compared with the results in the literature. Half of the cases (3 out of 6 eyes) which developed a retinal detachment had been horse-shoe tears combined with a vitreous hemorrhage. For this reason a small buckle operation is recommended in these cases, to prevent further traction. Lattice degeneration should rather be observed than treated, except in special cases: This includes eyes where the fellow eye had a detachment from a lattice degeneration, cases in which one eye is blind from an uncured detachment or has no useful visual acuity, and eyes whose fellow eye has giant tears. In aphakic eyes treatment of lattice degeneration is recommended, because the incidence of detachment from these areas is high, especially in young aphakic cases. In one aphakic eye which had been photocoagulated several times the formation of a preretinal membrane was observed.

  18. Inherited Retinal Degenerative Clinical Trial Network. Addendum

    Science.gov (United States)

    2013-10-01

    inherited orphan retinal degenerative diseases and dry age-related macular degeneration (AMD) through the conduct of clinical trials and other...design and conduct of effective and efficient clinical trials for inherited orphan retinal degenerative diseases and dry AMD; • Limited number and...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa, and the ProgSTAR studies for Stargardt disease ) . As new interventions b

  19. Frequency of lattice degeneration and retinal breaks in the fellow eye in retinal detachment.

    Science.gov (United States)

    Lorentzen, S E

    1988-04-01

    The fellow eye of 100 consecutively admitted cases of retinal detachment was studied with three-mirror examination for the presence of lattice degeneration and retinal breaks. Lattice degeneration was found in 18% and retinal breaks in 20% of fellow eyes.

  20. Optical coherence tomography study of retinal changes in normal aging and after ischemia.

    Science.gov (United States)

    Shariati, Mohammad Ali; Park, Joyce Ho; Liao, Yaping Joyce

    2015-05-01

    Age-related thinning of the retinal ganglion cell axons in the nerve fiber layer has been measured in humans using optical coherence tomography (OCT). In this study, we used OCT to measure inner retinal changes in 3-month-, 1-year-, and 2-year-old mice and after experimental anterior ischemic optic neuropathy (AION). We used OCT to quantify retinal thickness in over 200 eyes at different ages before and after a photochemical thrombosis model of AION. The scans were manually or automatically segmented. In normal aging, there was 1.3-μm thinning of the ganglion cell complex (GCC) between 3 months and 1 year (P < 0.0001) and no further thinning at 2 years. In studying age-related inner retinal changes, measurement of the GCC (circular scan) was superior to that of the total retinal thickness (posterior pole scan) despite the need for manual segmentation because it was not contaminated by outer retinal changes. Three weeks after AION, there was 8.9-μm thinning of the GCC (circular scan; P < 0.0001), 50-μm thinning of the optic disc (posterior pole scan; P < 0.0001), and 17-μm thinning of the retina (posterior pole scan; P < 0.0001) in the 3-month-old group. Changes in the older eyes after AION were similar to those of the 3-month-old group. Optical coherence tomography imaging of a large number of eyes showed that, like humans, mice exhibited small, age-related inner retinal thinning. Measurement of the GCC was superior to total retinal thickness in quantifying age-related changes, and both circular and posterior pole scans were useful to track short-term changes after AION.

  1. Bistatic SAR: Imagery & Image Products.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Wahl, Daniel E.; Jakowatz, Charles V,

    2014-10-01

    While typical SAR imaging employs a co-located (monostatic) RADAR transmitter and receiver, bistatic SAR imaging separates the transmitter and receiver locations. The transmitter and receiver geometry determines if the scattered signal is back scatter, forward scatter, or side scatter. The monostatic SAR image is backscatter. Therefore, depending on the transmitter/receiver collection geometry, the captured imagery may be quite different that that sensed at the monostatic SAR. This document presents imagery and image products formed from captured signals during the validation stage of the bistatic SAR research. Image quality and image characteristics are discussed first. Then image products such as two-color multi-view (2CMV) and coherent change detection (CCD) are presented.

  2. Resolution Enhancement of Multilook Imagery

    Energy Technology Data Exchange (ETDEWEB)

    Galbraith, Amy E. [Univ. of Arizona, Tucson, AZ (United States)

    2004-07-01

    This dissertation studies the feasibility of enhancing the spatial resolution of multi-look remotely-sensed imagery using an iterative resolution enhancement algorithm known as Projection Onto Convex Sets (POCS). A multi-angle satellite image modeling tool is implemented, and simulated multi-look imagery is formed to test the resolution enhancement algorithm. Experiments are done to determine the optimal con guration and number of multi-angle low-resolution images needed for a quantitative improvement in the spatial resolution of the high-resolution estimate. The important topic of aliasing is examined in the context of the POCS resolution enhancement algorithm performance. In addition, the extension of the method to multispectral sensor images is discussed and an example is shown using multispectral confocal fluorescence imaging microscope data. Finally, the remote sensing issues of atmospheric path radiance and directional reflectance variations are explored to determine their effect on the resolution enhancement performance.

  3. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    Finally, real-time PCR results showed that mtDNA and targeted genes of NF-κB were upregulated 3-fold in HREC after TFAM .... expression, real-time PCR mixture system containing primers ... operating as a previously reported method with.

  4. Visuospatial imagery and working memory in schizophrenia.

    Science.gov (United States)

    Matthews, Natasha L; Collins, Kathleen P; Thakkar, Katharine N; Park, Sohee

    2014-01-01

    The ability to form mental images that reconstruct former perceptual experiences is closely related to working memory (WM) ability. However, whereas WM deficits are established as a core feature of schizophrenia, an independent body of work suggests that mental imagery ability is enhanced in the disorder. Across two experiments we investigated mental imagery in schizophrenia and its relationship with WM. In Experiment 1, individuals with schizophrenia (SZ: n=15) and matched controls (CO: n=14) completed a mental imagery generation and inspection task and a spatial delayed-response WM task. In Experiment 2, SZ (n=16) and CO (n=16) completed a novel version of the mental imagery task modified to increase WM maintenance demand. In Experiment 1, SZ demonstrated enhanced mental imagery performance, as evidenced by faster response times relative to CO, with preserved accuracy. However, enhanced mental imagery in SZ was accompanied by impaired WM as assessed by the delayed-response task. In Experiment 2, when WM maintenance load was increased, SZ no longer showed superior imagery performance. We found evidence for enhanced imagery manipulation in SZ despite their WM maintenance deficit. However, this imagery enhancement was abolished when WM maintenance demands were increased. This profile of enhanced imagery manipulation but impaired maintenance could be used to implement novel remediation strategies in the disorder.

  5. User Validation of VIIRS Satellite Imagery

    Directory of Open Access Journals (Sweden)

    Don Hillger

    2015-12-01

    Full Text Available Visible/Infrared Imaging Radiometer Suite (VIIRS Imagery from the Suomi National Polar-orbiting Partnership (S-NPP satellite is the finest spatial resolution (375 m multi-spectral imagery of any operational meteorological satellite to date. The Imagery environmental data record (EDR has been designated as a Key Performance Parameter (KPP for VIIRS, meaning that its performance is vital to the success of a series of Joint Polar Satellite System (JPSS satellites that will carry this instrument. Because VIIRS covers the high-latitude and Polar Regions especially well via overlapping swaths from adjacent orbits, the Alaska theatre in particular benefits from VIIRS more than lower-latitude regions. While there are no requirements that specifically address the quality of the EDR Imagery aside from the VIIRS SDR performance requirements, the value of VIIRS Imagery to operational users is an important consideration in the Cal/Val process. As such, engaging a wide diversity of users constitutes a vital part of the Imagery validation strategy. The best possible image quality is of utmost importance. This paper summarizes the Imagery Cal/Val Team’s quality assessment in this context. Since users are a vital component to the validation of VIIRS Imagery, specific examples of VIIRS imagery applied to operational needs are presented as an integral part of the post-checkout Imagery validation.

  6. Retinal Cell Degeneration in Animal Models

    Directory of Open Access Journals (Sweden)

    Masayuki Niwa

    2016-01-01

    Full Text Available The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced, autoimmune (experimental autoimmune encephalomyelitis, mechanical stress (optic nerve crush-induced, light-induced and ischemia (transient retinal ischemia-induced. The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.

  7. Retinal Macroglial Responses in Health and Disease

    Directory of Open Access Journals (Sweden)

    Rosa de Hoz

    2016-01-01

    Full Text Available Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB, play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD, diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies.

  8. Coincidence of retinitis pigmentosa and pseudoexfoliative glaucoma

    Directory of Open Access Journals (Sweden)

    Božić Marija

    2017-01-01

    Full Text Available Introduction. This is an observational case report presenting retinitis pigmentosa associated with pseudoexfoliative glaucoma. Case outline. A 69-year-old man presented with retinitis pigmentosa. On examination, pseudoexfoliative material was detected on anterior segment structures, and intraocular pressure was 26 mmHg in the right and 24 mmHg in the left eye. The patient was commenced on topical antiglaucomatous therapy (timolol + dorzolamide twice daily, latanoprost once in the evening to both eyes. Conclusion. To the best of our knowledge, this is the first reported case of retinitis pigmentosa associated with pseudoexfoliative glaucoma. Although rare, retinitis pigmentosa and glaucoma can occur in the same eye.

  9. Retinal phlebitis associated with autoimmune hemolytic anemia.

    Science.gov (United States)

    Chew, Fiona L M; Tajunisah, Iqbal

    2009-01-01

    To describe a case of retinal phlebitis associated with autoimmune hemolytic anemia. Observational case report. A 44-year-old Indian man diagnosed with autoimmune hemolytic anemia presented with a 1-week history of blurred vision in both eyes. Fundus biomicroscopy revealed bilateral peripheral retinal venous sheathing and cellophane maculopathy. Fundus fluorescent angiogram showed bilateral late leakage from the peripheral venous arcades and submacular fluid accumulation. The retinal phlebitis resolved following a blood transfusion and administration of systemic steroids. Retinopathy associated with autoimmune hemolytic anemia is not well known. This is thought to be the first documentation of retinal phlebitis occurring in this condition.

  10. Tractional retinal detachment in Usher syndrome type II.

    Science.gov (United States)

    Rani, Alka; Pal, Nikhil; Azad, Raj Vardhan; Sharma, Yog Raj; Chandra, Parijat; Vikram Singh, Deependra

    2005-08-01

    Retinal detachment is a rare complication in patients with retinitis pigmentosa. A case is reported of tractional retinal detachment in a patient with retinitis pigmentosa and sensorineural hearing loss, which was diagnosed as Usher syndrome type II. Because of the poor visual prognosis, the patient refused surgery in that eye. Tractional retinal detachment should be added to the differential diagnoses of visual loss in patients with retinitis pigmentosa.

  11. Stem Cell-Based Therapeutic Applications in Retinal Degenerative Diseases.

    OpenAIRE

    Huang Yiming; Enzmann Volker; Ildstad Suzanne T

    2011-01-01

    Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinal degeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inheri...

  12. Landsat imagery: a unique resource

    Science.gov (United States)

    Miller, H.; Sexton, N.; Koontz, L.

    2011-01-01

    Landsat satellites provide high-quality, multi-spectral imagery of the surface of the Earth. These moderate-resolution, remotely sensed images are not just pictures, but contain many layers of data collected at different points along the visible and invisible light spectrum. These data can be manipulated to reveal what the Earth’s surface looks like, including what types of vegetation are present or how a natural disaster has impacted an area (Fig. 1).

  13. SirT1—A Sensor for Monitoring Self-Renewal and Aging Process in Retinal Stem Cells

    Directory of Open Access Journals (Sweden)

    Chi-Hsien Peng

    2010-06-01

    Full Text Available Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1, a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H2O2 treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H2O2-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1. SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.

  14. A question of intention in motor imagery.

    Science.gov (United States)

    Gabbard, Carl; Cordova, Alberto; Lee, Sunghan

    2009-03-01

    We examined the question-is the intention of completing a simulated motor action the same as the intention used in processing overt actions? Participants used motor imagery to estimate distance reachability in two conditions: Imagery-Only (IO) and Imagery-Execution (IE). With IO (red target) only a verbal estimate using imagery was given. With IE (green target) participants knew that they would actually reach after giving a verbal estimate and be judged on accuracy. After measuring actual maximum reach, used for the comparison, imagery targets were randomly presented across peripersonal- (within reach) and extrapersonal (beyond reach) space. Results indicated no difference in overall accuracy by condition, however, there was a significant distinction by space; participants were more accurate in peripersonal space. Although more research is needed, these findings support an increasing body of evidence suggesting that the neurocognitive processes (in this case, intention) driving motor imagery and overt actions are similar.

  15. Pornographic imagery and prevalence of paraphilia.

    Science.gov (United States)

    Dietz, P E; Evans, B

    1982-11-01

    The authors classified 1,760 heterosexual pornographic magazines according to the imagery of the cover photographs. Covers depicting only a woman posed alone predominated in 1970 but constituted only 10.7% of the covers in 1981. Bondage and domination imagery was the most prevalent nonormative imagery and was featured in 17.2% of the magazines. Smaller proportions of material were devoted to group sexual activity (9.8%), tranvestism and transsexualism (4.4%), and other nonnormative imagery. The authors suggest that pornographic imagery is an unobtrusive measure of the relative prevalence of those paraphilias associated with preferences for specific types of visual imagery and for which better data are lacking.

  16. Endogenous retinal neural stem cell reprogramming for neuronal regeneration

    Directory of Open Access Journals (Sweden)

    Romain Madelaine

    2017-01-01

    Full Text Available In humans, optic nerve injuries and associated neurodegenerative diseases are often followed by permanent vision loss. Consequently, an important challenge is to develop safe and effective methods to replace retinal neurons and thereby restore neuronal functions and vision. Identifying cellular and molecular mechanisms allowing to replace damaged neurons is a major goal for basic and translational research in regenerative medicine. Contrary to mammals, the zebrafish has the capacity to fully regenerate entire parts of the nervous system, including retina. This regenerative process depends on endogenous retinal neural stem cells, the Müller glial cells. Following injury, zebrafish Müller cells go back into cell cycle to proliferate and generate new neurons, while mammalian Müller cells undergo reactive gliosis. Recently, transcription factors and microRNAs have been identified to control the formation of new neurons derived from zebrafish and mammalian Müller cells, indicating that cellular reprogramming can be an efficient strategy to regenerate human retinal neurons. Here we discuss recent insights into the use of endogenous neural stem cell reprogramming for neuronal regeneration, differences between zebrafish and mammalian Müller cells, and the need to pursue the identification and characterization of new molecular factors with an instructive and potent function in order to develop theurapeutic strategies for eye diseases.

  17. ACCURACY COMPARISON OF VHR SYSTEMATIC-ORTHO SATELLITE IMAGERIES AGAINST VHR ORTHORECTIFIED IMAGERIES USING GCP

    Directory of Open Access Journals (Sweden)

    E. Widyaningrum

    2016-06-01

    Full Text Available The Very High Resolution (VHR satellite imageries such us Pleiades, WorldView-2, GeoEye-1 used for precise mapping purpose must be corrected from any distortion to achieve the expected accuracy. Orthorectification is performed to eliminate geometric errors of the VHR satellite imageries. Orthorectification requires main input data such as Digital Elevation Model (DEM and Ground Control Point (GCP. The VHR systematic-ortho imageries were generated using SRTM 30m DEM without using any GCP data. The accuracy value differences of VHR systematic-ortho imageries and VHR orthorectified imageries using GCP currently is not exactly defined. This study aimed to identified the accuracy comparison of VHR systematic-ortho imageries against orthorectified imageries using GCP. Orthorectified imageries using GCP created by using Rigorous model. Accuracy evaluation is calculated by using several independent check points.

  18. Normal central retinal function and structure preserved in retinitis pigmentosa.

    Science.gov (United States)

    Jacobson, Samuel G; Roman, Alejandro J; Aleman, Tomas S; Sumaroka, Alexander; Herrera, Waldo; Windsor, Elizabeth A M; Atkinson, Lori A; Schwartz, Sharon B; Steinberg, Janet D; Cideciyan, Artur V

    2010-02-01

    To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the central retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the central retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only central islands. The retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of retina warrants further study.

  19. Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions.

    NARCIS (Netherlands)

    Koenekoop, R.K.; Lopez, I.; Hollander, A.I. den; Allikmets, R.; Cremers, F.P.M.

    2007-01-01

    Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene-specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular

  20. Results of Automated Retinal Image Analysis for Detection of Diabetic Retinopathy from the Nakuru Study, Kenya

    DEFF Research Database (Denmark)

    Juul Bøgelund Hansen, Morten; Abramoff, M. D.; Folk, J. C.

    2015-01-01

    Objective Digital retinal imaging is an established method of screening for diabetic retinopathy (DR). It has been established that currently about 1% of the world's blind or visually impaired is due to DR. However, the increasing prevalence of diabetes mellitus and DR is creating an increased...... workload on those with expertise in grading retinal images. Safe and reliable automated analysis of retinal images may support screening services worldwide. This study aimed to compare the Iowa Detection Program (IDP) ability to detect diabetic eye diseases (DED) to human grading carried out at Moorfields...... predictive value of IDP versus the human grader as reference standard. Results Altogether 3,460 participants were included. 113 had DED, giving a prevalence of 3.3%(95% CI, 2.7-3.9%). Sensitivity of the IDP to detect DED as by the human grading was 91.0%(95% CI, 88.0-93.4%). The IDP ability to detect DED...

  1. Unconscious Imagination and the Mental Imagery Debate

    Directory of Open Access Journals (Sweden)

    Berit Brogaard

    2017-05-01

    Full Text Available Traditionally, philosophers have appealed to the phenomenological similarity between visual experience and visual imagery to support the hypothesis that there is significant overlap between the perceptual and imaginative domains. The current evidence, however, is inconclusive: while evidence from transcranial brain stimulation seems to support this conclusion, neurophysiological evidence from brain lesion studies (e.g., from patients with brain lesions resulting in a loss of mental imagery but not a corresponding loss of perception and vice versa indicates that there are functional and anatomical dissociations between mental imagery and perception. Assuming that the mental imagery and perception do not overlap, at least, to the extent traditionally assumed, then the question arises as to what exactly mental imagery is and whether it parallels perception by proceeding via several functionally distinct mechanisms. In this review, we argue that even though there may not be a shared mechanism underlying vision for perception and conscious imagery, there is an overlap between the mechanisms underlying vision for action and unconscious visual imagery. On the basis of these findings, we propose a modification of Kosslyn’s model of imagery that accommodates unconscious imagination and explore possible explanations of the quasi-pictorial phenomenology of conscious visual imagery in light of the fact that its underlying neural substrates and mechanisms typically are distinct from those of visual experience.

  2. Sensory Substitution and Multimodal Mental Imagery.

    Science.gov (United States)

    Nanay, Bence

    2017-09-01

    Many philosophers use findings about sensory substitution devices in the grand debate about how we should individuate the senses. The big question is this: Is "vision" assisted by (tactile) sensory substitution really vision? Or is it tactile perception? Or some sui generis novel form of perception? My claim is that sensory substitution assisted "vision" is neither vision nor tactile perception, because it is not perception at all. It is mental imagery: visual mental imagery triggered by tactile sensory stimulation. But it is a special form of mental imagery that is triggered by corresponding sensory stimulation in a different sense modality, which I call "multimodal mental imagery."

  3. Kinesthetic motor imagery modulates body sway.

    Science.gov (United States)

    Rodrigues, E C; Lemos, T; Gouvea, B; Volchan, E; Imbiriba, L A; Vargas, C D

    2010-08-25

    The aim of this study was to investigate the effect of imagining an action implicating the body axis in the kinesthetic and visual motor imagery modalities upon the balance control system. Body sway analysis (measurement of center of pressure, CoP) together with electromyography (EMG) recording and verbal evaluation of imagery abilities were obtained from subjects during four tasks, performed in the upright position: to execute bilateral plantar flexions; to imagine themselves executing bilateral plantar flexions (kinesthetic modality); to imagine someone else executing the same movement (visual modality), and to imagine themselves singing a song (as a control imagery task). Body sway analysis revealed that kinesthetic imagery leads to a general increase in CoP oscillation, as reflected by an enhanced area of displacement. This effect was also verified for the CoP standard deviation in the medial-lateral direction. An increase in the trembling displacement (equivalent to center of pressure minus center of gravity) restricted to the anterior-posterior direction was also observed to occur during kinesthetic imagery. The visual imagery task did not differ from the control (sing) task for any of the analyzed parameters. No difference in the subjects' ability to perform the imagery tasks was found. No modulation of EMG data were observed across imagery tasks, indicating that there was no actual execution during motor imagination. These results suggest that motor imagery performed in the kinesthetic modality evokes motor representations involved in balance control. Copyright (c)10 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Assessment of motor imagery ability and training

    Directory of Open Access Journals (Sweden)

    André Luiz Felix Rodacki

    2010-09-01

    Full Text Available The aim of this study was to evaluate changes in motor imagery ability in response to a specific dart throwing training. Twelve subjects (17-22 years with no previous experience in dart throwing or imagery agreed to participate. Changes in imagery ability were assessed using the Sports Imagery Questionnaire before (pretreatment and after (post-treatment an imagery training program consisting of 10 sessions. Retention (RET was assessed 2 weeks after training. The program included mental exercises designed to develop vivid images, to control one’s own images, and to increase perception about performance. Comparison of the imagery training conditions (training alone, training accompanied, observing a colleague, and during assessment showed no differences between the pretreatment, post-treatment and RET evaluations. Although imagery ability did not respond to training, significant differences between imagery domains (visual, auditory, kinesthetic, and animic were found (p<0.05, except between the visual and animic domains (p=0.58. These differences might be related to subject’s domain preference subject during the imagery process and to the nature of the task in which the skill technique used seems to be a relevant aspect.

  5. Retinal vein occlusion: pathophysiology and treatment options

    OpenAIRE

    Karia, Niral

    2010-01-01

    Niral KariaDepartment of Ophthalmology, Southend Hospital, Prittlewell Chase, Westcliff on Sea, Essex, United KingdomAbstract: This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.Keywords: central, hemispheric, branch, retinal vein occlusion, visual loss

  6. Retinitis pigmentosa, Coats disease and uveitis.

    Science.gov (United States)

    Solomon, A; Banin, E; Anteby, I; Benezra, D

    1999-01-01

    To study the anamnestic immune response to retinal specific antigens of two patients suffering from a rare triad of retinitis pigmentosa, Coats disease and uveitis. 17-year-old girl presented with an acute episode of panuveitis, and her 19-year-old brother suffered from chronic uveitis. On examination, both patients showed retinal vascular changes and subretinal exudations typical of Coats disease, with bone-spicule pigmentary changes as observed in retinitis pigmentosa. All routine examinations were unrevealing. However, the peripheral lymphocytes from these two siblings gave a specific anamnestic response to retinal antigens in vitro. A stimulation index of 4.6 was obtained when the sister's lymphocytes were stimulated with interphotoreceptor binding protein, IRBP--during the acute stage of the uveitis. The brother's lymphocytes showed a stimulation index of 2.7 towards S-Ag during the chronic phase of his uveitic condition. These results indicate that autoimmunity towards retinal antigens may play some role in specific types of retinitis pigmentosa. Whether these autoimmune reactions are a primary pathological mechanism or are secondary to the extensive destruction of the photoreceptor layer resulting from the retinitis pigmentosa remains debatable.

  7. Fundus autofluorescence applications in retinal imaging

    Science.gov (United States)

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-01-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  8. Fundus autofluorescence applications in retinal imaging

    Directory of Open Access Journals (Sweden)

    Andrea Gabai

    2015-01-01

    Full Text Available Fundus autofluorescence (FAF is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications.

  9. The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa

    DEFF Research Database (Denmark)

    Riess, O; Noerremoelle, A; Weber, B

    1992-01-01

    The finding of a mutation in the beta subunit of the cyclic GMP (cGMP) phosphodiesterase gene causing retinal degeneration in mice (the Pdeb gene) prompted a search for disease-causing mutations in the human phosphodiesterase gene (PDEB gene) in patients with retinitis pigmentosa. All 22 exons...

  10. Rhegmatogenous retinal detachment and uveitis.

    Science.gov (United States)

    Kerkhoff, Frank T; Lamberts, Querin J; van den Biesen, Pieter R; Rothova, Aniki

    2003-02-01

    To evaluate the frequency, high-risk factors, and visual prognosis of rhegmatogenous retinal detachment (RRD) in patients with uveitis. Retrospective case-control study. We included 1387 consecutive patients with uveitis who consulted our uveitis clinic from January 1990 through December 1997 of whom 43 patients (46 eyes) with RRD were identified. The retinal detachment (RD) controls were 212 consecutive patients with RRD (221 eyes, first occurrence of RD, not associated with uveitis) who were admitted for surgery in the period from April 1999 to April 2000. The uveitis control group consisted of 150 age-matched patients (210 eyes) selected from the entire uveitis series. Retrospective analysis of clinical data. The presence of RRD and eventual risk factors for RRD, such as myopia, retinal lattice degeneration, prior intraocular surgery, anatomic location of uveitis, its specific diagnosis, and clinical manifestations. Furthermore, the surgical and nonsurgical outcomes of RRD, as well as the results of various treatment regimens, were analyzed. RRD was identified in 3.1% of the patients with uveitis. RRD was most frequently associated with panuveitis (6.6%). RRD was associated more frequently with infectious (7.6%) than noninfectious uveitis (2.1%). At the onset of RRD, uveitis was active in most (46%) affected eyes. Proliferative vitreoretinopathy was present in 30% of the uveitic RRD eyes at presentation in contrast to 12% of the RRD control eyes. In uveitic RRD, the retina was reattached in 59% of eyes with a single operation; the final anatomic reattachment rate was 88%. Finally, a visual acuity of less than 20/200 was present in 71% of the uveitic RRD eyes, 10% of which had no light perception. We discovered a high prevalence of RRD in patients with active panuveitis and infectious uveitis and document that uveitis in itself is a risk factor for the development of RRD. The visual prognosis of RRD in uveitis was poor because of the uveitis itself and the

  11. User's Self-Prediction of Performance in Motor Imagery Brain-Computer Interface.

    Science.gov (United States)

    Ahn, Minkyu; Cho, Hohyun; Ahn, Sangtae; Jun, Sung C

    2018-01-01

    Performance variation is a critical issue in motor imagery brain-computer interface (MI-BCI), and various neurophysiological, psychological, and anatomical correlates have been reported in the literature. Although the main aim of such studies is to predict MI-BCI performance for the prescreening of poor performers, studies which focus on the user's sense of the motor imagery process and directly estimate MI-BCI performance through the user's self-prediction are lacking. In this study, we first test each user's self-prediction idea regarding motor imagery experimental datasets. Fifty-two subjects participated in a classical, two-class motor imagery experiment and were asked to evaluate their easiness with motor imagery and to predict their own MI-BCI performance. During the motor imagery experiment, an electroencephalogram (EEG) was recorded; however, no feedback on motor imagery was given to subjects. From EEG recordings, the offline classification accuracy was estimated and compared with several questionnaire scores of subjects, as well as with each subject's self-prediction of MI-BCI performance. The subjects' performance predictions during motor imagery task showed a high positive correlation ( r = 0.64, p performance even without feedback information. This implies that the human brain is an active learning system and, by self-experiencing the endogenous motor imagery process, it can sense and adopt the quality of the process. Thus, it is believed that users may be able to predict MI-BCI performance and results may contribute to a better understanding of low performance and advancing BCI.

  12. [To cognize retinitis pigmentosa with scientific view].

    Science.gov (United States)

    Li, Gen-lin

    2009-03-01

    Retinitis pigmentosa (RP) is the most common inherited eye disease that usually leads into blind, and is high simplex and clinical heterogeneity. Recent years, some new hereditary forms have been found, such as digenic RP, mitochondrial RP, incomplete dominant inheritance RP. The phenotype of RP is multiplicity. Incompatible phenomenon between genotype and phenotypes was shown in some genes such as peripherin/RDS, RHO, RP2 and RP3. The complicated phenotype was shown in the rare RP forms, such as centricity RP, stemma RP, retinitis pigmentosa sine pigmento, and retinal degeneration slow. Retinal transplantation, retinal implantation, drug and neurotrophic factor therapy, and gene therapy have been well studied worldwide and presented some hopeful efficacy. Ophthalmologists and practitioners should cognize the new advance and new knowledge on RP therapy with a scientific view for better serving the RP patients.

  13. [Indications for Retinal Laser Therapy Revisited].

    Science.gov (United States)

    Enders, P; Schaub, F; Fauser, S

    2017-02-10

    Background Laser therapy is an important treatment option in retinal diseases, especially in cases of vascular involvement. Most approaches are based on coagulation of retinal structures. As there is increasing use of agents targetting vascular endothelial growth factor in the treatment of macular diseases, indications for the use of laser treatment need to be reviewed carefully, especially with respect to their significance in first line therapy. This article explains recent strategies and treatment protocols. Materials and Methods Review of current literature in PubMed as well as synopsis of relevant guidelines. Results and Conclusion Retinal laser therapy is still widely used within retinal opthalmology and covers a large spectrum of indications. Despite the success of medical approaches, retinal laser therapy remains an indispensable treatment option for proliferative diabetic retinopathy, central or peripheral vein occlusion and less frequent pathologies, such as retinopathy of prematurity or Coats's disease. Georg Thieme Verlag KG Stuttgart · New York.

  14. OrthoImagery Submission for Isabella county, MI

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — This data set contains 1-meter resolution imagery derived from the 2005 National Agriculture Imagery Program (NAIP) statewide aerial imagery acquisition. Data have...

  15. Variable retinal presentations in nanophthalmos

    International Nuclear Information System (INIS)

    Khan, A.; Zafar, S.N.

    2009-01-01

    Nanophthalmos is an uncommon developmental ocular disorder characterized by a small eye with short axial length, high hyperopia and high lens/eye volume ratio due to arrested development of the globe in all directions. Different types of fundus changes can rarely occur with nanophthalmos. We describe five cases of nanophthalmos, each of them presenting with a different fundus appearance. Our case series highlights variability of pigmentary changes from retinal flecks to bone spicules and bull's eye maculopathy, which are rare in the combinations described here. (author)

  16. Regenerative Therapy for Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Narsis Daftarian

    2010-01-01

    Full Text Available Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.

  17. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    , the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer's formula and quantitative genetic models were used to determine the genetic component of variation. Results: The mean...... fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0...

  18. Retinal peripheral changes after LASIK

    OpenAIRE

    Nassaralla Junior,João Jorge; Santos,Regina Cândido Ribeiro dos; Nassaralla,Belquiz Amaral

    2008-01-01

    PURPOSE: To better define the effect of laser in situ keratomileusis (LASIK) on myopic eyes and the risk and incidence of retinal complications after surgery. METHODS: In a prospective study, 200 eyes of 100 patients, 49 male and 51 female, with a mean age of 29.7 years, had a complete posterior pole examination before and at 1 week, 1, 3 and 12 months after bilateral simultaneous LASIK for the correction of myopia. Mean spherical equivalent was 7.75D (range 1.00 to -17.25D). Before LASIK, pr...

  19. Thematic mapping from satellite imagery

    CERN Document Server

    Denègre, J

    2013-01-01

    Thematic Mapping from Satellite Imagery: A Guidebook discusses methods in producing maps using satellite images. The book is comprised of five chapters; each chapter covers one stage of the process. Chapter 1 tackles the satellite remote sensing imaging and its cartographic significance. Chapter 2 discusses the production processes for extracting information from satellite data. The next chapter covers the methods for combining satellite-derived information with that obtained from conventional sources. Chapter 4 deals with design and semiology for cartographic representation, and Chapter 5 pre

  20. Relationship between relaxation by guided imagery and performance of working memory.

    Science.gov (United States)

    Hudetz, J A; Hudetz, A G; Klayman, J

    2000-02-01

    This study tested the hypothesis that relaxation by guided imagery improves working-memory performance of healthy participants. 30 volunteers (both sexes, ages 17-56 years) were randomly assigned to one of three groups and administered the WAIS-III Letter-Number Sequencing Test before and after 10-min. treatment with guided imagery or popular music. The control group received no treatment. Groups' test scores were not different before treatment. The mean increased after relaxation by guided imagery but not after music or no treatment. This result supports the hypothesis that working-memory scores on the test are enhanced by guided imagery and implies that human information processing may be enhanced by prior relaxation.

  1. Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

    DEFF Research Database (Denmark)

    Kolko, M; Kiilgaard, J F; Wang, J

    2009-01-01

    Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used...... the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE...

  2. Quantum Biometrics with Retinal Photon Counting

    Science.gov (United States)

    Loulakis, M.; Blatsios, G.; Vrettou, C. S.; Kominis, I. K.

    2017-10-01

    It is known that the eye's scotopic photodetectors, rhodopsin molecules, and their associated phototransduction mechanism leading to light perception, are efficient single-photon counters. We here use the photon-counting principles of human rod vision to propose a secure quantum biometric identification based on the quantum-statistical properties of retinal photon detection. The photon path along the human eye until its detection by rod cells is modeled as a filter having a specific transmission coefficient. Precisely determining its value from the photodetection statistics registered by the conscious observer is a quantum parameter estimation problem that leads to a quantum secure identification method. The probabilities for false-positive and false-negative identification of this biometric technique can readily approach 10-10 and 10-4, respectively. The security of the biometric method can be further quantified by the physics of quantum measurements. An impostor must be able to perform quantum thermometry and quantum magnetometry with energy resolution better than 10-9ℏ , in order to foil the device by noninvasively monitoring the biometric activity of a user.

  3. Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.

    Science.gov (United States)

    Park, Susanna S

    2016-04-01

    Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.

  4. IMAGERY ANALYSIS ON EMILY DICKINSON’S POETRY

    Directory of Open Access Journals (Sweden)

    Masagus Sulaiman

    2017-03-01

    Full Text Available This research was conducted to figure out the imagery and its meanings in the five poetry of Emily Dickinson. This research was regarded on a descriptive-qualitative study. The researcher applied documentation technique in collecting the data. In data analysis, psychoanalytic approach by Kristeva was used. The results of the research showed that there were sixty-two types of imagery foundin the five poetry of Emily Dickinson, for instance; fifty-one visual, one auditory, one olfactory, three tactile, one organic and five kinesthetics. In addition, the five poetry of Emily Dickinson had something to do with the themes and meanings of humans’ livesand their relationship with their God that symbolized and illustrated by things, and personally regarded on the reflections of Emily Dickinson’s life.

  5. Alcohol imagery on New Zealand television

    Directory of Open Access Journals (Sweden)

    Reeder Anthony I

    2007-02-01

    Full Text Available Abstract Background To examine the extent and nature of alcohol imagery on New Zealand (NZ television, a content analysis of 98 hours of prime-time television programs and advertising was carried out over 7 consecutive days' viewing in June/July 2004. The main outcome measures were number of scenes in programs, trailers and advertisements depicting alcohol imagery; the extent of critical versus neutral and promotional imagery; and the mean number of scenes with alcohol per hour, and characteristics of scenes in which alcohol featured. Results There were 648 separate depictions of alcohol imagery across the week, with an average of one scene every nine minutes. Scenes depicting uncritical imagery outnumbered scenes showing possible adverse health consequences of drinking by 12 to 1. Conclusion The evidence points to a large amount of alcohol imagery incidental to storylines in programming on NZ television. Alcohol is also used in many advertisements to market non-alcohol goods and services. More attention needs to be paid to the extent of alcohol imagery on television from the industry, the government and public health practitioners. Health education with young people could raise critical awareness of the way alcohol imagery is presented on television.

  6. Imagery, Music, Cognitive Style and Memory.

    Science.gov (United States)

    Stratton, Valerie N.; Zalanowski, Annette

    Paired associate memory was tested with imagery and repetition instructions, with and without background music. Subjects were 64 students enrolled in an introductory psychology course. Music was found to have no effect with imagery instructions, but significantly improved performance with the repetition instructions. Music had different effects on…

  7. Mental Imagery in Creative Problem Solving.

    Science.gov (United States)

    Polland, Mark J.

    In order to investigate the relationship between mental imagery and creative problem solving, a study of 44 separate accounts reporting mental imagery experiences associated with creative discoveries were examined. The data included 29 different scientists, among them Albert Einstein and Stephen Hawking, and 9 artists, musicians, and writers,…

  8. Mental Imagery and Visual Working Memory

    Science.gov (United States)

    Keogh, Rebecca; Pearson, Joel

    2011-01-01

    Visual working memory provides an essential link between past and future events. Despite recent efforts, capacity limits, their genesis and the underlying neural structures of visual working memory remain unclear. Here we show that performance in visual working memory - but not iconic visual memory - can be predicted by the strength of mental imagery as assessed with binocular rivalry in a given individual. In addition, for individuals with strong imagery, modulating the background luminance diminished performance on visual working memory and imagery tasks, but not working memory for number strings. This suggests that luminance signals were disrupting sensory-based imagery mechanisms and not a general working memory system. Individuals with poor imagery still performed above chance in the visual working memory task, but their performance was not affected by the background luminance, suggesting a dichotomy in strategies for visual working memory: individuals with strong mental imagery rely on sensory-based imagery to support mnemonic performance, while those with poor imagery rely on different strategies. These findings could help reconcile current controversy regarding the mechanism and location of visual mnemonic storage. PMID:22195024

  9. Mental imagery and visual working memory.

    Directory of Open Access Journals (Sweden)

    Rebecca Keogh

    Full Text Available Visual working memory provides an essential link between past and future events. Despite recent efforts, capacity limits, their genesis and the underlying neural structures of visual working memory remain unclear. Here we show that performance in visual working memory--but not iconic visual memory--can be predicted by the strength of mental imagery as assessed with binocular rivalry in a given individual. In addition, for individuals with strong imagery, modulating the background luminance diminished performance on visual working memory and imagery tasks, but not working memory for number strings. This suggests that luminance signals were disrupting sensory-based imagery mechanisms and not a general working memory system. Individuals with poor imagery still performed above chance in the visual working memory task, but their performance was not affected by the background luminance, suggesting a dichotomy in strategies for visual working memory: individuals with strong mental imagery rely on sensory-based imagery to support mnemonic performance, while those with poor imagery rely on different strategies. These findings could help reconcile current controversy regarding the mechanism and location of visual mnemonic storage.

  10. Mental imagery and visual working memory.

    Science.gov (United States)

    Keogh, Rebecca; Pearson, Joel

    2011-01-01

    Visual working memory provides an essential link between past and future events. Despite recent efforts, capacity limits, their genesis and the underlying neural structures of visual working memory remain unclear. Here we show that performance in visual working memory--but not iconic visual memory--can be predicted by the strength of mental imagery as assessed with binocular rivalry in a given individual. In addition, for individuals with strong imagery, modulating the background luminance diminished performance on visual working memory and imagery tasks, but not working memory for number strings. This suggests that luminance signals were disrupting sensory-based imagery mechanisms and not a general working memory system. Individuals with poor imagery still performed above chance in the visual working memory task, but their performance was not affected by the background luminance, suggesting a dichotomy in strategies for visual working memory: individuals with strong mental imagery rely on sensory-based imagery to support mnemonic performance, while those with poor imagery rely on different strategies. These findings could help reconcile current controversy regarding the mechanism and location of visual mnemonic storage.

  11. Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells.

    Science.gov (United States)

    Li, Yao; Chan, Lawrence; Nguyen, Huy V; Tsang, Stephen H

    2016-01-01

    Interest in generating human induced pluripotent stem (iPS) cells for stem cell modeling of diseases has overtaken that of patient-specific human embryonic stem cells due to the ethical, technical, and political concerns associated with the latter. In ophthalmology, researchers are currently using iPS cells to explore various applications, including: (1) modeling of retinal diseases using patient-specific iPS cells; (2) autologous transplantation of differentiated retinal cells that undergo gene correction at the iPS cell stage via gene editing tools (e.g., CRISPR/Cas9, TALENs and ZFNs); and (3) autologous transplantation of patient-specific iPS-derived retinal cells treated with gene therapy. In this review, we will discuss the uses of patient-specific iPS cells for differentiating into retinal pigment epithelium (RPE) cells, uncovering disease pathophysiology, and developing new treatments such as gene therapy and cell replacement therapy via autologous transplantation.

  12. Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

    Science.gov (United States)

    Bianchi, Enrica; Ripandelli, Guido; Taurone, Samanta; Feher, Janos; Plateroti, Rocco; Kovacs, Illes; Magliulo, Giuseppe; Orlando, Maria Patrizia; Micera, Alessandra; Battaglione, Ezio; Artico, Marco

    2016-03-01

    Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes. © The Author(s) 2015.

  13. Apelin is a novel angiogenic factor in retinal endothelial cells

    International Nuclear Information System (INIS)

    Kasai, Atsushi; Shintani, Norihito; Oda, Maki; Kakuda, Michiya; Hashimoto, Hitoshi; Matsuda, Toshio; Hinuma, Shuji; Baba, Akemichi

    2004-01-01

    There has been much focus recently on the possible functions of apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, in cardiovascular and central nervous systems. We report a new function of apelin as a novel angiogenic factor in retinal endothelial cells. The retinal endothelial cell line RF/6A highly expressed both apelin and APJ transcripts, while human umbilical venous endothelial cells (HUVECs) only expressed apelin mRNA. In accordance with these observations, apelin at concentrations of 1 pM-1 μM significantly enhanced migration, proliferation, and capillary-like tube formation of RF/6A cells, but not those of HUVECs, whereas VEGF stimulates those parameters of both cell types. In vivo Matrigel plug assay for angiogenesis, the inclusion of 1 nM apelin in the Matrigel resulted in clear capillary-like formations with an increase of hemoglobin content in the plug. This is the first report showing that apelin is an angiogenic factor in retinal endothelial cells

  14. Recent Advancements in Gene Therapy for Hereditary Retinal Dystrophies

    Directory of Open Access Journals (Sweden)

    Ayşe Öner

    2017-12-01

    Full Text Available Hereditary retinal dystrophies (HRDs are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision, and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles, with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family, highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been proposed as potentially efficacious therapies. Because of its favorable anatomical and immunological characteristics, the eye has been at the forefront of translational gene therapy. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Dozens of promising proofs of concept have been obtained in animal models of HRDs and some of them have been relayed to the clinic. The results from the first clinical trials for a congenital form of blindness have generated great interest and have demonstrated the safety and efficacy of intraocular administrations of viral vectors in humans. This review summarizes the clinical development of retinal gene therapy.

  15. Observer perspective imagery with stuttering.

    Science.gov (United States)

    Lowe, Robyn; Menzies, Ross; Packman, Ann; O'Brian, Sue; Onslow, Mark

    2015-01-01

    Adults who stutter are at risk of developing a range of psychological conditions. Social anxiety disorder is the most common anxiety disorder associated with stuttering. Observer perspective imagery is one cognitive process involved in the maintenance of some anxiety disorders. This involves viewing images as if looking at the self from the perspective of another. In contrast, the field perspective involves looking out from the self at the surrounding environment. The purpose of this study was to assess the presence of observer perspective imagery with stuttering. The authors administered the Hackmann, Surawy and Clark (1998) semi-structured interview to 30 adults who stutter and 30 controls. Group images and impressions were compared for frequency, perspective recalled and emotional valence. The stuttering group was significantly more likely than controls to recall images and impressions from an observer rather than a field perspective for anxious situations. It is possible the present results could reflect the same attentional processing bias that occurs with anxiety disorders in the non-stuttering population. These preliminary results provide an explanation for the persistence of conditions such as social anxiety disorder with stuttering. Clinical implications are discussed.

  16. Renal-Retinal Ciliopathy Gene Sdccag8 Regulates DNA Damage Response Signaling

    DEFF Research Database (Denmark)

    Airik, Rannar; Slaats, Gisela G; Guo, Zhi

    2014-01-01

    Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and degenerative kidney diseases that are frequently associated with extrarenal pathologies such as retinal degeneration, obesity, and intellectual disability. We recently identified mutations in a gene encoding the centrosomal...... protein SDCCAG8 as causing NPHP type 10 in humans. To study the role of Sdccag8 in disease pathogenesis, we generated a Sdccag8 gene-trap mouse line. Homozygous Sdccag8(gt/gt) mice lacked the wild-type Sdccag8 transcript and protein, and recapitulated the human phenotypes of NPHP and retinal degeneration....... These mice exhibited early onset retinal degeneration that was associated with rhodopsin mislocalization in the photoreceptors and reduced cone cell numbers, and led to progressive loss of vision. By contrast, renal histologic changes occurred later, and no global ciliary defects were observed in the kidneys...

  17. Guided Imagery and Stress in Pregnant Adolescents.

    Science.gov (United States)

    Flynn, Theresa A; Jones, Brittney A; Ausderau, Karla K

    2016-01-01

    We examined the effects of a guided imagery intervention on perceived stress in pregnant adolescents. Thirty-five pregnant adolescents recruited from a local alternative education program participated in a guided imagery intervention. Participants listened to a pregnancy-specific guided imagery recording on four separate occasions during their pregnancies. Perceived stress was measured immediately before and after each session using the Perceived Stress Measure-9 (PSM-9). Participants' pre- and postsession PSM-9 scores for three of the four sessions demonstrated a significant reduction in stress. Participants' baseline stress levels also decreased significantly across the four listening sessions. The greatest reductions in stress within and between sessions occurred in the early sessions, with effects diminishing over time. Pregnant teens experienced initial short- and long-term stress reduction during a guided imagery intervention, supporting the use of guided imagery to reduce stress in pregnant adolescents. Copyright © 2016 by the American Occupational Therapy Association, Inc.

  18. BIGH3 protein and macrophages in retinal endothelial cell apoptosis.

    Science.gov (United States)

    Mondragon, Albert A; Betts-Obregon, Brandi S; Moritz, Robert J; Parvathaneni, Kalpana; Navarro, Mary M; Kim, Hong Seok; Lee, Chi Fung; LeBaron, Richard G; Asmis, Reto; Tsin, Andrew T

    2015-01-01

    Diabetes is a pandemic disease with a higher occurrence in minority populations. The molecular mechanism to initiate diabetes-associated retinal angiogenesis remains largely unknown. We propose an inflammatory pathway of diabetic retinopathy in which macrophages in the diabetic eye provide TGFβ to retinal endothelial cells (REC) in the retinal microvasculature. In response to TGFβ, REC synthesize and secrete a pro-apoptotic BIGH3 (TGFβ-Induced Gene Human Clone 3) protein, which acts in an autocrine loop to induce REC apoptosis. Rhesus monkey retinal endothelial cells (RhREC) were treated with dMCM (cell media of macrophages treated with high glucose and LDL) and assayed for apoptosis (TUNEL), BIGH3 mRNA (qPCR), and protein (Western blots) expressions. Cells were also treated with ΤGFβ1 and 2 for BIGH3 mRNA and protein expression. Inhibition assays were carried out using antibodies for TGFβ1 and for BIGH3 to block apoptosis and mRNA expression. BIGH3 in cultured RhREC cells were identified by immunohistochemistry (IHC). Distribution of BIGH3 and macrophages in the diabetic mouse retina was examined with IHC. RhRECs treated with dMCM or TGFβ showed a significant increase in apoptosis and BIGH3 protein expression. Recombinant BIGH3 added to RhREC culture medium led to a dose-dependent increase in apoptosis. Antibodies (Ab) directed against BIGH3 and TGFβ, as well as TGFβ receptor blocker resulted in a significant reduction in apoptosis induced by either dMCM, TGFβ or BIGH3. IHC showed that cultured RhREC constitutively expressed BIGH3. Macrophage and BIGH3 protein were co-localized to the inner retina of the diabetic mouse eye. Our results support a novel inflammatory pathway for diabetic retinopathy. This pathway is initiated by TGFβ released from macrophages, which promotes synthesis and release of BIGH3 protein by REC and REC apoptosis.

  19. The Argus(®) II Retinal Prosthesis System.

    Science.gov (United States)

    Luo, Yvonne Hsu-Lin; da Cruz, Lyndon

    2016-01-01

    The Argus(®) II Retinal Prosthesis System (Second Sight Medical Products) is the first prosthetic vision device to obtain regulatory approval in both Europe and the USA. As such it has entered the commercial market as a treatment for patients with profound vision loss from end-stage outer retinal disease, predominantly retinitis pigmentosa. To date, over 100 devices have been implanted worldwide, representing the largest group of patients currently treated with visual prostheses. The system works by direct stimulation of the relatively preserved inner retina via epiretinal microelectrodes, thereby replacing the function of the degenerated photoreceptors. Visual information from a glasses-mounted video camera is converted to a pixelated image by an external processor, before being transmitted to the microelectrode array at the macula. Elicited retinal responses are then relayed via the normal optic nerve to the cortex for interpretation. We reviewed the animal and human studies that led to the development of the Argus(®) II device. A sufficiently robust safety profile was demonstrated in the phase I/II clinical trial of 30 patients. Improvement of function in terms of orientation and mobility, target localisation, shape and object recognition, and reading of letters and short unrehearsed words have also been shown. There remains a wide variability in the functional outcomes amongst the patients and the factors contributing to these performance differences are still unclear. Future developments in terms of both software and hardware aimed at improving visual function have been proposed. Further experience in clinical outcomes is being acquired due to increasing implantation. Copyright © 2015. Published by Elsevier Ltd.

  20. Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa.

    Science.gov (United States)

    Arno, Gavin; Agrawal, Smriti A; Eblimit, Aiden; Bellingham, James; Xu, Mingchu; Wang, Feng; Chakarova, Christina; Parfitt, David A; Lane, Amelia; Burgoyne, Thomas; Hull, Sarah; Carss, Keren J; Fiorentino, Alessia; Hayes, Matthew J; Munro, Peter M; Nicols, Ralph; Pontikos, Nikolas; Holder, Graham E; Asomugha, Chinwe; Raymond, F Lucy; Moore, Anthony T; Plagnol, Vincent; Michaelides, Michel; Hardcastle, Alison J; Li, Yumei; Cukras, Catherine; Webster, Andrew R; Cheetham, Michael E; Chen, Rui

    2016-12-01

    Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Vehicle classification in WAMI imagery using deep network

    Science.gov (United States)

    Yi, Meng; Yang, Fan; Blasch, Erik; Sheaff, Carolyn; Liu, Kui; Chen, Genshe; Ling, Haibin

    2016-05-01

    Humans have always had a keen interest in understanding activities and the surrounding environment for mobility, communication, and survival. Thanks to recent progress in photography and breakthroughs in aviation, we are now able to capture tens of megapixels of ground imagery, namely Wide Area Motion Imagery (WAMI), at multiple frames per second from unmanned aerial vehicles (UAVs). WAMI serves as a great source for many applications, including security, urban planning and route planning. These applications require fast and accurate image understanding which is time consuming for humans, due to the large data volume and city-scale area coverage. Therefore, automatic processing and understanding of WAMI imagery has been gaining attention in both industry and the research community. This paper focuses on an essential step in WAMI imagery analysis, namely vehicle classification. That is, deciding whether a certain image patch contains a vehicle or not. We collect a set of positive and negative sample image patches, for training and testing the detector. Positive samples are 64 × 64 image patches centered on annotated vehicles. We generate two sets of negative images. The first set is generated from positive images with some location shift. The second set of negative patches is generated from randomly sampled patches. We also discard those patches if a vehicle accidentally locates at the center. Both positive and negative samples are randomly divided into 9000 training images and 3000 testing images. We propose to train a deep convolution network for classifying these patches. The classifier is based on a pre-trained AlexNet Model in the Caffe library, with an adapted loss function for vehicle classification. The performance of our classifier is compared to several traditional image classifier methods using Support Vector Machine (SVM) and Histogram of Oriented Gradient (HOG) features. While the SVM+HOG method achieves an accuracy of 91.2%, the accuracy of our deep

  2. Bilateral acute retinal necrosis after herpetic meningitis

    Directory of Open Access Journals (Sweden)

    Katsura T

    2012-04-01

    Full Text Available Keisho Hirota1,2, Masayuki Akimoto1,3, Toshiaki Katsura21Department of Ophthalmology, Kyoto Medical Center, National Hospital Organization, 2Internal Medicine, Kyoto Medical Center, 3Clinical Research Center, Kyoto Medical Center, Kyoto, JapanPurpose: The report of a case of bilateral acute retinal necrosis after herpetic meningitis.Case report: A 47-year-old man was admitted with the chief complaint of persistent high fever and transient loss of consciousness. Although his general condition improved after intravenous acyclovir administration, the patient presented with visual loss in both eyes 4 days after admission. Visual acuity in his right eye was 20/200 and his left eye had light perception alone. Both eyes showed panretinal arteritis diagnosed as acute retinal necrosis. Panretinal photocoagulation was performed for both eyes. Progression of retinal detachment was prevented in both eyes; however, visual acuity of the left eye was totally lost because of neovascular glaucoma. Visual acuity of the right eye recovered to 20/20.Conclusion: Although cases of bilateral acute retinal necrosis have been reported after herpetic encephalitis, this condition is rare after herpetic meningitis. Prophylactic acyclovir therapy and early panretinal photocoagulation may prevent retinal detachment and improve the prognosis. Neurologists and ophthalmologists should be aware that not only herpetic encephalitis but also herpetic meningitis can lead to acute retinal necrosis within a very short interval.Keywords: acute retinal necrosis, herpetic meningitis, herpes simplex, varicella zoster virus

  3. Retinitis pigmentosa, pigmentary retinopathies, and neurologic diseases.

    Science.gov (United States)

    Bhatti, M Tariq

    2006-09-01

    Retinitis pigmentosa (RP) refers to a group of inherited retinal diseases with phenotypic and genetic heterogeneity. The pathophysiologic basis of the progressive visual loss in patients with RP is not completely understood but is felt to be due to a primary retinal photoreceptor cell degenerative process mainly affecting the rods of the peripheral retina. In most cases RP is seen in isolation (nonsyndromic), but in some other cases it may be a part of a genetic, metabolic, or neurologic syndrome or disorder. Nyctalopia, or night blindness, is the most common symptom of RP. The classic fundus appearance of RP includes retinal pigment epithelial cell changes resulting in retinal hypo- or hyperpigmentation ("salt-and-pepper"), retinal granularity, and bone spicule formation. The retinal vessels are often narrowed or attenuated and there is a waxy pallor appearance of the optic nerve head. Electroretinography will demonstrate rod and cone photoreceptor cell dysfunction and is a helpful test in the diagnosis and monitoring of patients with RP. A detailed history with pedigree analysis, a complete ocular examination, and the appropriate paraclinical testing should be performed in patients complaining of visual difficulties at night or in dim light. This review discusses the clinical manifestations of RP as well as describing the various systemic diseases, with a special emphasis on neurologic diseases, associated with a pigmentary retinopathy.

  4. Genomic analysis of mouse retinal development.

    Directory of Open Access Journals (Sweden)

    Seth Blackshaw

    2004-09-01

    Full Text Available The vertebrate retina is comprised of seven major cell types that are generated in overlapping but well-defined intervals. To identify genes that might regulate retinal development, gene expression in the developing retina was profiled at multiple time points using serial analysis of gene expression (SAGE. The expression patterns of 1,051 genes that showed developmentally dynamic expression by SAGE were investigated using in situ hybridization. A molecular atlas of gene expression in the developing and mature retina was thereby constructed, along with a taxonomic classification of developmental gene expression patterns. Genes were identified that label both temporal and spatial subsets of mitotic progenitor cells. For each developing and mature major retinal cell type, genes selectively expressed in that cell type were identified. The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions. In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs" were found to be dynamically and specifically expressed in developing and mature retinal cell types. Finally, many photoreceptor-enriched genes that mapped to chromosomal intervals containing retinal disease genes were identified. These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

  5. Optical Coherence Tomography Angiography in Retinal Diseases.

    Science.gov (United States)

    Chalam, K V; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases.

  6. Silver nano - a trove for retinal therapies.

    Science.gov (United States)

    Kalishwaralal, Kalimuthu; Barathmanikanth, Selvaraj; Pandian, Sureshbabu Ram Kumar; Deepak, Venkatraman; Gurunathan, Sangiliyandi

    2010-07-14

    Pathological retinal angiogenesis (neovascularization) is one of the most feared complications among retinal diseases, leading to visual impairment and irreversible blindness. Recent findings made by us on therapeutic applications of biologically synthesized silver nanoparticles (AgNPs) against VEGF induced retinal endothelial cells, elucidates the effectual inhibitory activities of AgNPs over the downstream signaling pathways (Src and AKT/PI3K) leading to retinal angiogenesis. The current review focuses on the imperative role of VEGF induced angiogenesis in the development of retinal neovascularization and despite the fact that several VEGF targeting ocular drugs are available; the review examines the need for a cost economic alternative, thereby suggesting the role of AgNPs as an emerging economic ocular drug for retinal therapies. The current technologies available for the development of targeted and controlled release of drugs is being discussed and a model has been proposed for the amenable targeting mechanism, by which Poly gamma glutamic acid (PGA) capsulated AgNPs conjugated to cyclic RGD peptides carry out a sustained controlled release specifically targeting the neovascularization cells and induce apoptosis unaffecting the normal retinal cells. These constructs consequently affirm the futuristic application of silver nanoparticles as a boon to ocular therapies. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. 3D OCT imaging in clinical settings: toward quantitative measurements of retinal structures

    Science.gov (United States)

    Zawadzki, Robert J.; Fuller, Alfred R.; Zhao, Mingtao; Wiley, David F.; Choi, Stacey S.; Bower, Bradley A.; Hamann, Bernd; Izatt, Joseph A.; Werner, John S.

    2006-02-01

    The acquisition speed of current FD-OCT (Fourier Domain - Optical Coherence Tomography) instruments allows rapid screening of three-dimensional (3D) volumes of human retinas in clinical settings. To take advantage of this ability requires software used by physicians to be capable of displaying and accessing volumetric data as well as supporting post processing in order to access important quantitative information such as thickness maps and segmented volumes. We describe our clinical FD-OCT system used to acquire 3D data from the human retina over the macula and optic nerve head. B-scans are registered to remove motion artifacts and post-processed with customized 3D visualization and analysis software. Our analysis software includes standard 3D visualization techniques along with a machine learning support vector machine (SVM) algorithm that allows a user to semi-automatically segment different retinal structures and layers. Our program makes possible measurements of the retinal layer thickness as well as volumes of structures of interest, despite the presence of noise and structural deformations associated with retinal pathology. Our software has been tested successfully in clinical settings for its efficacy in assessing 3D retinal structures in healthy as well as diseased cases. Our tool facilitates diagnosis and treatment monitoring of retinal diseases.

  8. Paediatric retinal detachment: aetiology, characteristics and outcomes

    Directory of Open Access Journals (Sweden)

    Elizabeth McElnea

    2018-02-01

    Full Text Available AIM: To provide contemporary data on the aetiology, clinical features and outcomes of paediatric retinal detachment. METHODS: A retrospective review of all those under 16y who underwent surgical repair for retinal detachment at a single centre between the years 2008 and 2015 inclusive was performed. In each case the cause of retinal detachment, the type of detachment, the presence or absence of macular involvement, the number and form of reparative surgeries undertaken, and the surgical outcome achieved was recorded. RESULTS: Twenty-eight eyes of 24 patients, 15 (62.5% of whom were male and 9 (37.5% of whom were female, their mean age being 11.6y and range 2-16y developed retinal detachment over the eight year period studied. Trauma featured in the development of retinal detachment in 14 (50.0% cases. Retinal detachment was associated with other ocular and/or systemic conditions in 11 (39.3% cases. A mean of 3.0 procedures with a range of 1-9 procedures per patient were undertaken in the management of retinal detachment. Complex vitrectomy combined with scleral buckling or complex vitrectomy alone were those most frequently performed. Mean postoperative visual acuity was 1.2 logMAR with range 0.0-3.0 logMAR. In 22 of 26 (84.6% cases which underwent surgical repair the retina was attached at last follow-up. CONCLUSION: Aggressive management of paediatric retinal detachment including re-operation increases the likelihood of anatomical success. In cases where the retinal detachment can be repaired by an external approach alone there is a more favourable visual outcome.

  9. Paediatric retinal detachment: aetiology, characteristics and outcomes.

    Science.gov (United States)

    McElnea, Elizabeth; Stephenson, Kirk; Gilmore, Sarah; O'Keefe, Michael; Keegan, David

    2018-01-01

    To provide contemporary data on the aetiology, clinical features and outcomes of paediatric retinal detachment. A retrospective review of all those under 16y who underwent surgical repair for retinal detachment at a single centre between the years 2008 and 2015 inclusive was performed. In each case the cause of retinal detachment, the type of detachment, the presence or absence of macular involvement, the number and form of reparative surgeries undertaken, and the surgical outcome achieved was recorded. Twenty-eight eyes of 24 patients, 15 (62.5%) of whom were male and 9 (37.5%) of whom were female, their mean age being 11.6y and range 2-16y developed retinal detachment over the eight year period studied. Trauma featured in the development of retinal detachment in 14 (50.0%) cases. Retinal detachment was associated with other ocular and/or systemic conditions in 11 (39.3%) cases. A mean of 3.0 procedures with a range of 1-9 procedures per patient were undertaken in the management of retinal detachment. Complex vitrectomy combined with scleral buckling or complex vitrectomy alone were those most frequently performed. Mean postoperative visual acuity was 1.2 logMAR with range 0.0-3.0 logMAR. In 22 of 26 (84.6%) cases which underwent surgical repair the retina was attached at last follow-up. Aggressive management of paediatric retinal detachment including re-operation increases the likelihood of anatomical success. In cases where the retinal detachment can be repaired by an external approach alone there is a more favourable visual outcome.

  10. A clinical approach to the diagnosis of retinal vasculitis.

    Science.gov (United States)

    El-Asrar, Ahmed M Abu; Herbort, Carl P; Tabbara, Khalid F

    2010-04-01

    Retinal vasculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and is confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.

  11. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment

    OpenAIRE

    Mathew, David J.; Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were al...

  12. In vivo imaging of the retinal pigment epithelial cells

    Science.gov (United States)

    Morgan, Jessica Ijams Wolfing

    The retinal pigment epithelial (RPE) cells form an important layer of the retina because they are responsible for providing metabolic support to the photoreceptors. Techniques to image the RPE layer include autofluorescence imaging with a scanning laser ophthalmoscope (SLO). However, previous studies were unable to resolve single RPE cells in vivo. This thesis describes the technique of combining autofluorescence, SLO, adaptive optics (AO), and dual-wavelength simultaneous imaging and registration to visualize the individual cells in the RPE mosaic in human and primate retina for the first time in vivo. After imaging the RPE mosaic non-invasively, the cell layer's structure and regularity were characterized using quantitative metrics of cell density, spacing, and nearest neighbor distances. The RPE mosaic was compared to the cone mosaic, and RPE imaging methods were confirmed using histology. The ability to image the RPE mosaic led to the discovery of a novel retinal change following light exposure; 568 nm exposures caused an immediate reduction in autofluorescence followed by either full recovery or permanent damage in the RPE layer. A safety study was conducted to determine the range of exposure irradiances that caused permanent damage or transient autofluorescence reductions. Additionally, the threshold exposure causing autofluorescence reduction was determined and reciprocity of radiant exposure was confirmed. Light exposures delivered by the AOSLO were not significantly different than those delivered by a uniform source. As all exposures tested were near or below the permissible light levels of safety standards, this thesis provides evidence that the current light safety standards need to be revised. Finally, with the retinal damage and autofluorescence reduction thresholds identified, the methods of RPE imaging were modified to allow successful imaging of the individual cells in the RPE mosaic while still ensuring retinal safety. This thesis has provided a

  13. Smart image processing system for retinal prosthesis.

    Science.gov (United States)

    Weiland, James D; Parikh, Neha; Pradeep, Vivek; Medioni, Gerard

    2012-01-01

    Retinal prostheses for the blind have demonstrated the ability to provide the sensation of light in otherwise blind individuals. However, visual task performance in these patients remains poor relative to someone with normal vision. Computer vision algorithms for navigation and object detection were evaluated for their ability to improve task performance. Blind subjects navigating a mobility course had fewer collisions when using a wearable camera system that guided them on a safe path. Subjects using a retinal prosthesis simulator could locate objects more quickly when an object detection algorithm assisted them. Computer vision algorithms can assist retinal prosthesis patients and low-vision patients in general.

  14. Photostress Testing Device for Diagnosing Retinal Disease

    Directory of Open Access Journals (Sweden)

    Elizabeth Swan

    2014-08-01

    Full Text Available Retinal diseases such as Age-Related Macular Degeneration (ARMD affect nearly one in three elderly patients. ARMD damages the central vision photoreceptors in the fovea. The Photostress Test is a simple technique for testing for the early effects of ARMD. Here, the illumination sources in a novel self-administered Photostress Testing device were modeled for safety and distribution in illumination software. After satisfying the design constraints in the model, a prototype of the illumination system was fabricated and tested to confirm the modeling results. The resultant prototype can be used to aid in the diagnosis of retinal disease and is well within retinal safety levels.

  15. Mapping the Distribution of Cloud Forests Using MODIS Imagery

    Science.gov (United States)

    Douglas, M. W.; Mejia, J.; Murillo, J.; Orozco, R.

    2007-05-01

    Tropical cloud forests - those forests that are frequently immersed in clouds or otherwise very humid, are extremely difficult to map from the ground, and are not easily distinguished in satellite imagery from other forest types, but they have a very different flora and fauna than lowland rainforest. Cloud forests, although found in many parts of the tropics, have a very restricted vertical extent and thus are also restricted horizontally. As a result, they are subject to both human disturbance (coffee growing for example) and the effects of possible climate change. Motivated by a desire to seek meteorological explanations for the distribution of cloud forests, we have begun to map cloudiness using MODIS Terra and Aqua visible imagery. This imagery, at ~1030 LT and 1330 LT, is an approximation for mid-day cloudiness. In tropical regions the amount of mid-day cloudiness strongly controls the shortwave radiation and thus the potential for evaporation (and aridity). We have mapped cloudiness using a simple algorithm that distinguishes between the cloud-free background brightness and the generally more reflective clouds to separate clouds from the underlying background. A major advantage of MODIS imagery over many other sources of satellite imagery is its high spatial resolution (~250m). This, coupled with precisely navigated images, means that detailed maps of cloudiness can be produced. The cloudiness maps can then be related to the underlying topography to further refine the location of the cloud forests. An advantage of this technique is that we are mapping the potential cloud forest, based on cloudiness, rather than the actual cloud forest, which are commonly based on forest estimates from satellite and digital elevation data. We do not derive precipitation, only estimates of daytime cloudiness. Although only a few years of MODIS imagery has been used in our studies, we will show that this is sufficient to describe the climatology of cloudiness with acceptable

  16. Treatment of Retinal Separation in HIV-infected Patients with Cytomegalovirus Retinitis

    Directory of Open Access Journals (Sweden)

    A. L. Onischenko

    2017-01-01

    Full Text Available HIV infection — is a socially significant problem for many countries, as the infected die in an average of 10-11 years due to the immunodeficiency virus. Up to 20% of patients with AIDS lose their sight because of cytomegalovirus retinitis (CMV retinitis, which occurs in 70% of HIV-infected people. In some patients with HIV infection blindness occurs because of acute retinal necrosis of CMV etiology. The algorithm of CMV retinitis treatment in HIV-infected patients is described in modern manuals (ganciclovir, valganciclovir, foscarnet and others on the background of antiretroviral therapy, but the tactics of treatment of retinal separation in these patients is not clearly defined. It may be “wait and see”, providing conservative treatment with antiviral drugs, and the active tactics — vitreoretinal surgery. In this article the authors present their personal clinical observations of three HIV-infected patients with CMV retinitis at the age of 8 to 36 years with a detailed analysis of the clinical data and the results of the laboratory tests. In particular, the authors give their own results of intravitreal introduction of ganciclovir in patients with CMV retinitis. Given the poor prognosis for the life of these patients, the authors put a deontological question of justification of active treatment of retinal separation in AIDS patients with CMV retinitis.

  17. Retinal Endovascular Surgery with Tissue Plasminogen Activator Injection for Central Retinal Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Yuta Takata

    2018-06-01

    Full Text Available Purpose: To report 2 cases of central retinal artery occlusion (CRAO who underwent retinal endovascular surgery with injection of tissue plasminogen activator (tPA into the retinal artery and showed a remarkable improvement in visual acuity and retinal circulation. Methods: Standard 25-G vitrectomy was performed under local anesthesia. Simultaneously, tPA (80,000 units/mL solution was injected into the retinal artery of the optic disc for 2–3 min using a microneedle. Changes in visual acuity, fundus photography, optical coherence tomography (OCT, fluorescein angiography, and laser speckle flowgraphy (LSFG results were examined. Results: Both cases could be treated within 12 h after the onset of CRAO. Case 1 was a 47-year-old woman. Her visual acuity improved from counting fingers before operation to 0.08 logMAR 1 month after the surgery. However, thinning of the retina at the macula was observed by OCT. Case 2 was a 70-year-old man. His visual acuity improved from counting fingers to 0.1 logMAR 2 months after the surgery. Both fluorescein angiography and LSFG showed improvement in retinal circulation after the surgery in case 2. Conclusions: Retinal endovascular surgery with injection of tPA into the retinal artery was feasible and may be a way to improve visual acuity and retinal circulation when performed in the acute phase of CRAO.

  18. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti...... fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0.......0002) in monozygotic twins than in dizygotic twins (0.108, P = 0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, dominant genetic effects explained 54% of the variation and 46% was individually environmentally determined. Conclusions: In young adult twins...

  19. Musical Imagery Involves Wernicke's Area in Bilateral and Anti-Correlated Network Interactions in Musicians.

    Science.gov (United States)

    Zhang, Yizhen; Chen, Gang; Wen, Haiguang; Lu, Kun-Han; Liu, Zhongming

    2017-12-06

    Musical imagery is the human experience of imagining music without actually hearing it. The neural basis of this mental ability is unclear, especially for musicians capable of engaging in accurate and vivid musical imagery. Here, we created a visualization of an 8-minute symphony as a silent movie and used it as real-time cue for musicians to continuously imagine the music for repeated and synchronized sessions during functional magnetic resonance imaging (fMRI). The activations and networks evoked by musical imagery were compared with those elicited by the subjects directly listening to the same music. Musical imagery and musical perception resulted in overlapping activations at the anterolateral belt and Wernicke's area, where the responses were correlated with the auditory features of the music. Whereas Wernicke's area interacted within the intrinsic auditory network during musical perception, it was involved in much more complex networks during musical imagery, showing positive correlations with the dorsal attention network and the motor-control network and negative correlations with the default-mode network. Our results highlight the important role of Wernicke's area in forming vivid musical imagery through bilateral and anti-correlated network interactions, challenging the conventional view of segregated and lateralized processing of music versus language.

  20. Automated analysis of autoradiographic imagery

    International Nuclear Information System (INIS)

    Bisignani, W.T.; Greenhouse, S.C.

    1975-01-01

    A research programme is described which has as its objective the automated characterization of neurological tissue regions from autoradiographs by utilizing hybrid-resolution image processing techniques. An experimental system is discussed which includes raw imagery, scanning an digitizing equipments, feature-extraction algorithms, and regional characterization techniques. The parameters extracted by these algorithms are presented as well as the regional characteristics which are obtained by operating on the parameters with statistical sampling techniques. An approach is presented for validating the techniques and initial experimental results are obtained from an anlysis of an autoradiograph of a region of the hypothalamus. An extension of these automated techniques to other biomedical research areas is discussed as well as the implications of applying automated techniques to biomedical research problems. (author)

  1. Accommodative loss after retinal cryotherapy.

    Science.gov (United States)

    Uno, Tsuyoshi; Okuyama, Michiko; Tanabe, Tatsuro; Kawamura, Ryosuke; Ideta, Hidenao

    2009-01-01

    To investigate the effects of peripheral retinal cryotherapy on accommodative amplitude in patients with retinal lattice degeneration. Prospective, observational case series. We studied 92 eyes in 69 patients (age range, 13 to 79 years) treated with cryotherapy for lattice degeneration between December 2001 and September 2004. Pretreatment and posttreatment accommodative amplitudes were measured. Acute accommodative loss was calculated from the difference between accommodative amplitudes before treatment and one week after treatment. We investigated the time course of accommodative amplitudes, acute accommodative loss in different age groups and in pretreatment accommodative amplitude groups, the influence of cryotherapy numbers on accommodative amplitude, and the influence of cryotherapy sites on accommodative amplitude. No significant difference was noted between pretreatment and posttreatment accommodative amplitudes in the overall subject cohort. Dividing subjects by age revealed significant decreases in accommodative amplitude only among patients in their 10s and 20s at one and three weeks after treatment. Accommodative amplitude was lowest among those in their 10s, followed by that among those in their 20s (P < .01). Accommodative amplitudes recovered to pretreatment level by six weeks. Acute accommodative loss was greatest in those in their 10s compared with other age groups (P < .01). A significant correlation was observed between acute accommodative loss and cryotherapy numbers (P = .03; r = 0.41). The decrease in accommodative amplitude was greatest at one week after treatment and recovered to pretreatment levels after six weeks. Accommodative amplitude showed the greatest decrease after cryotherapy among patients in their 10s and 20s. A decrease in accommodative amplitude was observed with increased numbers of cryotherapy spots administered.

  2. The neural correlates of visual imagery: A co-ordinate-based meta-analysis.

    Science.gov (United States)

    Winlove, Crawford I P; Milton, Fraser; Ranson, Jake; Fulford, Jon; MacKisack, Matthew; Macpherson, Fiona; Zeman, Adam

    2018-01-02

    Visual imagery is a form of sensory imagination, involving subjective experiences typically described as similar to perception, but which occur in the absence of corresponding external stimuli. We used the Activation Likelihood Estimation algorithm (ALE) to identify regions consistently activated by visual imagery across 40 neuroimaging studies, the first such meta-analysis. We also employed a recently developed multi-modal parcellation of the human brain to attribute stereotactic co-ordinates to one of 180 anatomical regions, the first time this approach has been combined with the ALE algorithm. We identified a total 634 foci, based on measurements from 464 participants. Our overall comparison identified activation in the superior parietal lobule, particularly in the left hemisphere, consistent with the proposed 'top-down' role for this brain region in imagery. Inferior premotor areas and the inferior frontal sulcus were reliably activated, a finding consistent with the prominent semantic demands made by many visual imagery tasks. We observed bilateral activation in several areas associated with the integration of eye movements and visual information, including the supplementary and cingulate eye fields (SCEFs) and the frontal eye fields (FEFs), suggesting that enactive processes are important in visual imagery. V1 was typically activated during visual imagery, even when participants have their eyes closed, consistent with influential depictive theories of visual imagery. Temporal lobe activation was restricted to area PH and regions of the fusiform gyrus, adjacent to the fusiform face complex (FFC). These results provide a secure foundation for future work to characterise in greater detail the functional contributions of specific areas to visual imagery. Copyright © 2017. Published by Elsevier Ltd.

  3. Mental imagery of gravitational motion.

    Science.gov (United States)

    Gravano, Silvio; Zago, Myrka; Lacquaniti, Francesco

    2017-10-01

    There is considerable evidence that gravitational acceleration is taken into account in the interaction with falling targets through an internal model of Earth gravity. Here we asked whether this internal model is accessed also when target motion is imagined rather than real. In the main experiments, naïve participants grasped an imaginary ball, threw it against the ceiling, and caught it on rebound. In different blocks of trials, they had to imagine that the ball moved under terrestrial gravity (1g condition) or under microgravity (0g) as during a space flight. We measured the speed and timing of the throwing and catching actions, and plotted ball flight duration versus throwing speed. Best-fitting duration-speed curves estimate the laws of ball motion implicit in the participant's performance. Surprisingly, we found duration-speed curves compatible with 0g for both the imaginary 0g condition and the imaginary 1g condition, despite the familiarity with Earth gravity effects and the added realism of performing the throwing and catching actions. In a control experiment, naïve participants were asked to throw the imaginary ball vertically upwards at different heights, without hitting the ceiling, and to catch it on its way down. All participants overestimated ball flight durations relative to the durations predicted by the effects of Earth gravity. Overall, the results indicate that mental imagery of motion does not have access to the internal model of Earth gravity, but resorts to a simulation of visual motion. Because visual processing of accelerating/decelerating motion is poor, visual imagery of motion at constant speed or slowly varying speed appears to be the preferred mode to perform the tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. A consonant construction of the hyaloid and retinal vascular systems by the angiogenic process.

    Science.gov (United States)

    Gergely, K; Gerinec, A

    2011-01-01

    There has been much debate as to whether the retinal vasculature forms by angiogenesis or vasculogenesis, thus angiogenesis is now accepted. We suppose that signals necessary for proper localization and development of the hyaloid and retinal vascular systems are already in place prior to the time at which these systems are developed. The remarkable conservation of vascular patterning suggests that specific genetic programs coordinate its formation. Evidence for a genetic program comes particularly from the characterization of gene-targeted mice and mutational analysis in zebrafish, but the exact genetic pathways remain poorly defined. Considering all the things from the aspect of angiogenesis significant differences exist between the mentioned vascular systems only in their lifetime (a) and location (b): (a) The hyaloid vasculature is a complex of transient intraocular vessels, while the retinal vessels are adapted for the whole life. (b) The hyaloid system fills the interior of the optic cup and this way "occupies" three-dimensional space while the distribution of the retinal vessels is relatively planar (two-dimensional) in the retina. We assume that retinal vessels are "built" in the same manner as the hyaloid vasculature and the outcomes at the embryological, histological, cellular and molecular levels confirm it. We show a consonant construction of both systems. The human organism does not have any rational reason to build up one system (i.e. the hyaloid vasculature) by angiogenesis and practically the same system (i.e. the retinal vessels) by another, de novo process, in the eye. It would be a waste of energy and various essential molecules. Thus, it seems that the retinal vascular system is an advanced copy of the hyaloid vessels (Tab. 1, Ref. 143).

  5. Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.

    Science.gov (United States)

    Fu, Jinling; Nagashima, Mikiko; Guo, Chuanyu; Raymond, Pamela A; Wei, Xiangyun

    2018-01-01

    Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts. Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.

  6. Conventional Microscopy vs. Computer Imagery in Chiropractic Education.

    Science.gov (United States)

    Cunningham, Christine M; Larzelere, Elizabeth D; Arar, Ilija

    2008-01-01

    As human tissue pathology slides become increasingly difficult to obtain, other methods of teaching microscopy in educational laboratories must be considered. The purpose of this study was to evaluate our students' satisfaction with newly implemented computer imagery based laboratory instruction and to obtain input from their perspective on the advantages and disadvantages of computerized vs. traditional microscope laboratories. This undertaking involved the creation of a new computer laboratory. Robbins and Cotran Pathologic Basis of Disease, 7(th)ed, was chosen as the required text which gave students access to the Robbins Pathology website, including complete content of text, Interactive Case Study Companion, and Virtual Microscope. Students had experience with traditional microscopes in their histology and microbiology laboratory courses. Student satisfaction with computer based learning was assessed using a 28 question survey which was administered to three successive trimesters of pathology students (n=193) using the computer survey website Zoomerang. Answers were given on a scale of 1-5 and statistically analyzed using weighted averages. The survey data indicated that students were satisfied with computer based learning activities during pathology laboratory instruction. The most favorable aspect to computer imagery was 24-7 availability (weighted avg. 4.16), followed by clarification offered by accompanying text and captions (weighted avg. 4.08). Although advantages and disadvantages exist in using conventional microscopy and computer imagery, current pathology teaching environments warrant investigation of replacing traditional microscope exercises with computer applications. Chiropractic students supported the adoption of computer-assisted instruction in pathology laboratories.

  7. Rhegmatogenous retinal detachment following intravitreal ocriplasmin

    NARCIS (Netherlands)

    Madi, Haifa A.; Haynes, Richard J.; Depla, Diana; de la Cour, Morten D.; Lesnik-Oberstein, Sarit; Muqit, Mahi M. K.; Patton, Niall; Price, Nick; Steel, David H. W.

    2016-01-01

    To describe the characteristics and outcomes of patients presenting with rhegmatogenous retinal detachment (RRD) after ocriplasmin (OCP) injection. Retrospective, multi-centre, observational case series with case note review. Eight patients with symptomatic vitreomacular traction (six with

  8. [Paediatric retinal detachment and hereditary vitreoretinal disorders].

    Science.gov (United States)

    Meier, P

    2013-09-01

    The number of retinal detachments in children is very low in comparison to the number in adults. One predisposing factor for development of paediatric retinal detachment is suffering from hereditary vitreoretinal degeneration (e.g., Stickler syndrome, Wagner syndrome, Kniest dysplasia, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, Knobloch syndrome, incontinentia pigmenti, Norrie disease). Hereditary vitreoretinopathies are characterised by an abnormal-appearing vitreous gel with associated retinal changes. In most of these eyes further ocular abnormalities can be diagnosed. A group of hereditary disorders is associated with characteristic systemic abnormalities. Allied conditions should be considered in the clinical diagnosis. Vitreoretinopathies are the most common cause of inherited retinal detachment. In most eyes primary vitrectomy is necessary, and disease-specific surgical treatment is discussed. Georg Thieme Verlag KG Stuttgart · New York.

  9. Retinal Detachment: Torn or Detached Retina Diagnosis

    Science.gov (United States)

    ... Feb 20, 2018 Gene Therapy May Be a Game-Changer for People With Inherited Retinal Disease Dec 19, 2017 ... the Academy Jobs at the Academy Financial Relationships with Industry Medical Disclaimer Privacy Policy Terms of Service For ...

  10. Retinal Detachment: Torn or Detached Retina Treatment

    Science.gov (United States)

    ... Feb 20, 2018 Gene Therapy May Be a Game-Changer for People With Inherited Retinal Disease Dec 19, 2017 ... the Academy Jobs at the Academy Financial Relationships with Industry Medical Disclaimer Privacy Policy Terms of Service For ...

  11. Retinal Detachment: Torn or Detached Retina Symptoms

    Science.gov (United States)

    ... Feb 20, 2018 Gene Therapy May Be a Game-Changer for People With Inherited Retinal Disease Dec 19, 2017 ... the Academy Jobs at the Academy Financial Relationships with Industry Medical Disclaimer Privacy Policy Terms of Service For ...

  12. Adaptive optics imaging of inherited retinal diseases.

    Science.gov (United States)

    Georgiou, Michalis; Kalitzeos, Angelos; Patterson, Emily J; Dubra, Alfredo; Carroll, Joseph; Michaelides, Michel

    2017-11-15

    Adaptive optics (AO) ophthalmoscopy allows for non-invasive retinal phenotyping on a microscopic scale, thereby helping to improve our understanding of retinal diseases. An increasing number of natural history studies and ongoing/planned interventional clinical trials exploit AO ophthalmoscopy both for participant selection, stratification and monitoring treatment safety and efficacy. In this review, we briefly discuss the evolution of AO ophthalmoscopy, recent developments and its application to a broad range of inherited retinal diseases, including Stargardt disease, retinitis pigmentosa and achromatopsia. Finally, we describe the impact of this in vivo microscopic imaging on our understanding of disease pathogenesis, clinical trial design and outcome metrics, while recognising the limitation of the small cohorts reported to date. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Regulatory and Economic Considerations of Retinal Drugs.

    Science.gov (United States)

    Shah, Ankoor R; Williams, George A

    2016-01-01

    The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs. © 2016 S. Karger AG, Basel.

  14. A CNGB1 frameshift mutation in Papillon and Phalene dogs with progressive retinal atrophy.

    Directory of Open Access Journals (Sweden)

    Saija J Ahonen

    Full Text Available Progressive retinal degenerations are the most common causes of complete blindness both in human and in dogs. Canine progressive retinal atrophy (PRA or degeneration resembles human retinitis pigmentosa (RP and is characterized by a progressive loss of rod photoreceptor cells followed by a loss of cone function. The primary clinical signs are detected as vision impairment in a dim light. Although several genes have been associated with PRAs, there are still PRAs of unknown genetic cause in many breeds, including Papillons and Phalènes. We have performed a genome wide association and linkage studies in cohort of 6 affected Papillons and Phalènes and 14 healthy control dogs to map a novel PRA locus on canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs. Parallel exome sequencing of a trio identified an indel mutation, including a 1-bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes a frameshift and premature stop codon leading to probable nonsense mediated decay (NMD of the CNGB1 mRNA. The mutation segregated with the disease and was confirmed in a larger cohort of 145 Papillons and Phalènes (PFisher = 1.4×10(-8 with a carrier frequency of 17.2 %. This breed specific mutation was not present in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other breeds. CNGB1 is important for the photoreceptor cell function its defects have been previously associated with retinal degeneration in both human and mouse. Our study indicates that a frameshift mutation in CNGB1 is a cause of PRA in Papillons and Phalènes and establishes the breed as a large functional animal model for further characterization of retinal CNGB1 biology and possible retinal gene therapy trials. This study enables also the development of a genetic test for breeding purposes.

  15. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress.

    Science.gov (United States)

    Arredondo Zamarripa, David; Díaz-Lezama, Nundehui; Meléndez García, Rodrigo; Chávez Balderas, Jesús; Adán, Norma; Ledesma-Colunga, Maria G; Arnold, Edith; Clapp, Carmen; Thebault, Stéphanie

    2014-01-01

    Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK) production contributes to the increased transport through the blood-retina barrier (BRB) in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE) components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO) synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC), blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC) monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19) cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS) in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  16. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress

    Directory of Open Access Journals (Sweden)

    David eArredondo Zamarripa

    2014-10-01

    Full Text Available Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK production contributes to the increased transport through the blood-retina barrier (BRB in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC, blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19 cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  17. The Sport Imagery Questionnaire for Children (SIQ-C)

    Science.gov (United States)

    Hall, C. R.; Munroe-Chandler, K. J.; Fishburne, G. J.; Hall, N. D.

    2009-01-01

    Athletes of all ages report using imagery extensively to enhance their sport performance. The Sport Imagery Questionnaire (Hall, Mack, Paivio, & Hausenblas, 1998) was developed to assess cognitive and motivational imagery used by adult athletes. No such instrument currently exists to measure the use of imagery by young athletes. The aim of the…

  18. Optic Disc Pit with Sectorial Retinitis Pigmentosa

    OpenAIRE

    Balikoglu-Yilmaz, Melike; Taskapili, Muhittin; Yilmaz, Tolga; Teke, Mehmet Yasin

    2013-01-01

    Sectorial retinitis pigmentosa (RP) and optic disc pit (ODP) are rare clinical conditions. We present a 40-year-old woman with a history of mild night blindness and decreased vision in the right eye for about 5 years. Fundus examination revealed retinal pigmentary changes in the superior and inferotemporal sectors covering the macula and reduced arterial calibre and ODP at the temporal edge of the optic disc. In addition, fundus autofluorescence, spectral-domain optical coherence tomography, ...

  19. Retinal function in deaf-blind syndromes

    OpenAIRE

    Malm, Eva

    2011-01-01

    A variety of disorders can cause retinal degeneration and hearing impairment, and it is of great value to have an early diagnosis since there is a large variation in phenotype and prognosis both within and between the different disorders. The general aim of this thesis was to characterize the retinal function, to describe the phenotype, and – where appropriate – to relate the phenotype to genotype in patients with combined visual and hearing impairment. Alström syndrome is a rare auto...

  20. Branch retinal artery occlusion in Susac's syndrome

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2015-02-01

    Full Text Available Susac's syndrome is a rare disease attribuited to a microangiopathy involving the arterioles of the cochlea, retina and brain. Encefalopathy, hearing loss, and visual deficits are the hallmarks of the disease. Visual loss is due to multiple, recurrent branch arterial retinal occlusions. We report a case of a 20-year-old women with Susac syndrome presented with peripheral vestibular syndrome, hearing loss, ataxia, vertigo, and vision loss due occlusion of the retinal branch artery.

  1. Current surgery of retinal detachment recurrence. Review

    Directory of Open Access Journals (Sweden)

    V. D. Zakharov

    2012-01-01

    Full Text Available this review presents a detailed analysis and an experience of surgical treatment of retinal detachment recurrence associated with light silicone oil tamponade of vitreous cavity. Approaches and variants of treatment were described in the historical aspect and till now. there are considered general and particular issues in case of retinal detachment recurrence appearance, expediency and volume of intraoperative manipulations, time of operation and choice of temporary substitute of vitreous body for a purpose of postoperative tamponade of vitreous cavity.

  2. CCR7 signaling pathway and retinal neovascularization

    Directory of Open Access Journals (Sweden)

    Lin-Hui Yuan

    2015-11-01

    Full Text Available Retinal neovascularization diseases are the major causes of blindness. C-C chemokine receptor type 7(CCR7can promote the expression of vascular endothelial growth factor(VEGFthrough the extracellular signal regulated kinase(ERKpathway, leading to vascular leakage, proliferation of vascular endothelial cell, neovascularization and etc. The detection of CCR7 can guide the diagnosis and treatments of retinal neovascularization diseases.

  3. Safety of iPhone retinal photography.

    Science.gov (United States)

    Hong, Sheng Chiong; Wynn-Williams, Giles; Wilson, Graham

    2017-04-01

    With the advancement in mobile technology, smartphone retinal photography is becoming a popular practice. However, there is limited information about the safety of the latest smartphones used for retinal photography. This study aims to determine the photobiological risk of iPhone 6 and iPhone 6 plus when used in conjunction with a 20Diopter condensing lens for retinal photography. iPhone 6 and iPhone 6 plus (Apple, Cupertino, CA) were used in this study. The geometrical setup of the study was similar to the indirect ophthalmoscopy technique. The phone was set up at one end of the bench with its flash turned on at maximal brightness; a 20 Dioptre lens was placed 15 cm away from the phone. The light that passes through the lens was measured with a spectroradiometer and an illuminance probe at the other end to determine the spectral profile, spatial irradiance, radiant power emitted by the phone's flash. Trigonometric and lens formula were applied to determine the field of view and retinal surface in order to determine the weighted retinal irradiance and weighted retinal radiant exposure. Taking ocular transmission and the distribution of the beam's spatial irradiance into account, the weighted retinal irradiance is 1.40 mW/cm 2 and the weighted retinal radiant exposure is 56.25 mJ/cm 2 . The peak weighted foveal irradiance is 1.61 mW/cm 2 . Our study concluded that the photobiological risk posed by iPhone 6 indirect ophthalmoscopy was at least 1 order of magnitude below the safety limits set by the ISO15004-2.2.

  4. Multipoint linkage analysis and homogeneity tests in 15 Dutch X-linked retinitis pigmentosa families

    NARCIS (Netherlands)

    Bergen, A. A.; van den Born, L. I.; Schuurman, E. J.; Pinckers, A. J.; van Ommen, G. J.; Bleekers-Wagemakers, E. M.; Sandkuijl, L. A.

    1995-01-01

    Linkage analysis and homogeneity tests were carried out in 15 Dutch families segregating X-linked retinitis pigmentosa (X L R P). The study included segregation data for eight polymorphic DNA markers from the short arm of the human X chromosome. The results of both multipoint linkage analysis in

  5. Connective tissue growth factor is necessary for retinal capillary basal lamina thickening in diabetic mice

    NARCIS (Netherlands)

    Kuiper, Esther J.; van Zijderveld, Rogier; Roestenberg, Peggy; Lyons, Karen M.; Goldschmeding, Roel; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Schlingemann, Reinier O.

    2008-01-01

    Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components. We hypothesize

  6. Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration.

    NARCIS (Netherlands)

    Yang, Z.; Alvarez, B.V.; Chakarova, C.; Jiang, L.; Karan, G.; Frederick, J.M.; Zhao, Y.; Sauve, Y.; Li, X.; Zrenner, E.; Wissinger, B.; Hollander, A.I. den; Katz, B.; Baehr, W.; Cremers, F.P.M.; Casey, J.R.; Bhattacharya, S.S.; Zhang, K.

    2005-01-01

    Retina and retinal pigment epithelium (RPE) belong to the metabolically most active tissues in the human body. Efficient removal of acid load from retina and RPE is a critical function mediated by the choriocapillaris. However, the mechanism by which pH homeostasis is maintained is largely unknown.

  7. An approach for flood monitoring by the combined use of Landsat 8 optical imagery and COSMO-SkyMed radar imagery

    Science.gov (United States)

    Tong, Xiaohua; Luo, Xin; Liu, Shuguang; Xie, Huan; Chao, Wei; Liu, Shuang; Liu, Shijie; Makhinov, A. N.; Makhinova, A. F.; Jiang, Yuying

    2018-02-01

    Remote sensing techniques offer potential for effective flood detection with the advantages of low-cost, large-scale, and real-time surface observations. The easily accessible data sources of optical remote sensing imagery provide abundant spectral information for accurate surface water body extraction, and synthetic aperture radar (SAR) systems represent a powerful tool for flood monitoring because of their all-weather capability. This paper introduces a new approach for flood monitoring by the combined use of both Landsat 8 optical imagery and COSMO-SkyMed radar imagery. Specifically, the proposed method applies support vector machine and the active contour without edges model for water extent determination in the periods before and during the flood, respectively. A map difference method is used for the flood inundation analysis. The proposed approach is particularly suitable for large-scale flood monitoring, and it was tested on a serious flood that occurred in northeastern China in August 2013, which caused immense loss of human lives and properties. High overall accuracies of 97.46% for the optical imagery and 93.70% for the radar imagery are achieved by the use of the techniques presented in this study. The results show that about 12% of the whole study area was inundated, corresponding to 5466 km2 of land surface.

  8. Assessing Deep Sea Communities Through Seabed Imagery

    Science.gov (United States)

    Matkin, A. G.; Cross, K.; Milititsky, M.

    2016-02-01

    The deep sea still remains virtually unexplored. Human activity, such as oil and gas exploration and deep sea mining, is expanding further into the deep sea, increasing the need to survey and map extensive areas of this habitat in order to assess ecosystem health and value. The technology needed to explore this remote environment has been advancing. Seabed imagery can cover extensive areas of the seafloor and investigate areas where sampling with traditional coring methodologies is just not possible (e.g. cold water coral reefs). Remotely operated vehicles (ROVs) are an expensive option, so drop or towed camera systems can provide a more viable and affordable alternative, while still allowing for real-time control. Assessment of seabed imagery in terms of presence, abundance and density of particular species can be conducted by bringing together a variety of analytical tools for a holistic approach. Sixteen deep sea transects located offshore West Africa were investigated with a towed digital video telemetry system (DTS). Both digital stills and video footage were acquired. An extensive data set was obtained from over 13,000 usable photographs, allowing for characterisation of the different habitats present in terms of community composition and abundance. All observed fauna were identified to the lowest taxonomic level and enumerated when possible, with densities derived after the seabed area was calculated for each suitable photograph. This methodology allowed for consistent assessment of the different habitat types present, overcoming constraints, such as specific taxa that cannot be enumerated, such as sponges, corals or bryozoans, the presence of mobile and sessile species, or the level of taxonomic detail. Although this methodology will not enable a full characterisation of a deep sea community, in terms of species composition for instance, itt will allow a robust assessment of large areas of the deep sea in terms of sensitive habitats present and community

  9. Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

    Directory of Open Access Journals (Sweden)

    Michele Bertacchi

    2015-10-01

    Full Text Available Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine.

  10. User-guided segmentation for volumetric retinal optical coherence tomography images

    Science.gov (United States)

    Yin, Xin; Chao, Jennifer R.; Wang, Ruikang K.

    2014-01-01

    Abstract. Despite the existence of automatic segmentation techniques, trained graders still rely on manual segmentation to provide retinal layers and features from clinical optical coherence tomography (OCT) images for accurate measurements. To bridge the gap between this time-consuming need of manual segmentation and currently available automatic segmentation techniques, this paper proposes a user-guided segmentation method to perform the segmentation of retinal layers and features in OCT images. With this method, by interactively navigating three-dimensional (3-D) OCT images, the user first manually defines user-defined (or sketched) lines at regions where the retinal layers appear very irregular for which the automatic segmentation method often fails to provide satisfactory results. The algorithm is then guided by these sketched lines to trace the entire 3-D retinal layer and anatomical features by the use of novel layer and edge detectors that are based on robust likelihood estimation. The layer and edge boundaries are finally obtained to achieve segmentation. Segmentation of retinal layers in mouse and human OCT images demonstrates the reliability and efficiency of the proposed user-guided segmentation method. PMID:25147962

  11. Protective effect of basic fibroblast growth factor on retinal injury induced by argon laser photocoagulation

    International Nuclear Information System (INIS)

    Chen, P; San, Q; Wang, C Z; Yang, Z F; Kang, H X; Qian, H W; Zhang, C P

    2010-01-01

    Laser photocoagulation treatment is often complicated by a side effect of visual impairment, which is caused by the unavoidable laser-induced retinal destruction. At present no specific is found to cure this retinopathy. The aim of this study was to observe the neuroprotective effect of bFGF on laser-induced retinal injury. Chinchilla rabbits were divided into three groups and argon laser lesions were created in the retinas. Then bFGF or dexamethasone, a widely used ophthalmic preparation, or saline was given severally by retrobulbar injection. The retinal lesions were evaluated histologically and morphometrically, and visual function was examined by ERG. The results showed that bFGF administration better preserved morphology of retinal photoreceptors and significantly diminished the area of the lesions. Furthermore, bFGF promoted the restoration of the ERG b-wave amplitude. In rabbits treated with dexamethasone, however, the lesions showed almost no ameliorative changes. This is the first study to investigate the potential role of bFGF as a remedial agent in laser photocoagulation treatment. These findings suggest that bFGF has significant neuroprotective properties in the retina and this type of neuroprotection may be of clinical significance in reducing iatrogenic laser-induced retinal injuries in humans

  12. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

    Science.gov (United States)

    Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

  13. Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

    Science.gov (United States)

    Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

    2018-02-14

    Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

  14. Technical brief: a comparison of two methods of euthanasia on retinal dopamine levels.

    Science.gov (United States)

    Hwang, Christopher K; Iuvone, P Michael

    2013-01-01

    Mice are commonly used in biomedical research, and euthanasia is an important part of mouse husbandry. Approved, humane methods of euthanasia are designed to minimize the potential for pain or discomfort, but may also influence the measurement of experimental variables. We compared the effects of two approved methods of mouse euthanasia on the levels of retinal dopamine. We examined the level of retinal dopamine, a commonly studied neuromodulator, following euthanasia by carbon dioxide (CO₂)-induced asphyxiation or by cervical dislocation. We found that the level of retinal dopamine in mice euthanized through CO₂ overdose substantially differed from that in mice euthanized through cervical dislocation. The use of CO₂ as a method of euthanasia could result in an experimental artifact that could compromise results when studying labile biologic processes.

  15. 2012 Oconee County, Georgia ADS80 Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — All imagery was collected during the 2012 Spring flying season during leaf-off conditions for deciduous vegetation in the State of Georgia. The sun angle was at...

  16. Competence imagery: a case study treating emetophobia.

    Science.gov (United States)

    Moran, Daniel J; O'Brien, Richard M

    2005-06-01

    An emetophobic child is nonresponsive to conventional systematic desensitization and has her anxiety responses counterconditioned by using Competence Imagery instead of physical relaxation responses while progressing through her fear hierarchy.

  17. Mental imagery boosts music compositional creativity.

    Science.gov (United States)

    Wong, Sarah Shi Hui; Lim, Stephen Wee Hun

    2017-01-01

    We empirically investigated the effect of mental imagery on young children's music compositional creativity. Children aged 5 to 8 years participated in two music composition sessions. In the control session, participants based their composition on a motif that they had created using a sequence of letter names. In the mental imagery session, participants were given a picture of an animal and instructed to imagine the animal's sounds and movements, before incorporating what they had imagined into their composition. Six expert judges independently rated all music compositions on creativity based on subjective criteria (consensual assessment). Reliability analyses indicated that the expert judges demonstrated a high level of agreement in their ratings. The mental imagery compositions received significantly higher creativity ratings by the expert judges than did the control compositions. These results provide evidence for the effectiveness of mental imagery in enhancing young children's music compositional creativity.

  18. Mental imagery boosts music compositional creativity

    Science.gov (United States)

    Lim, Stephen Wee Hun

    2017-01-01

    We empirically investigated the effect of mental imagery on young children’s music compositional creativity. Children aged 5 to 8 years participated in two music composition sessions. In the control session, participants based their composition on a motif that they had created using a sequence of letter names. In the mental imagery session, participants were given a picture of an animal and instructed to imagine the animal’s sounds and movements, before incorporating what they had imagined into their composition. Six expert judges independently rated all music compositions on creativity based on subjective criteria (consensual assessment). Reliability analyses indicated that the expert judges demonstrated a high level of agreement in their ratings. The mental imagery compositions received significantly higher creativity ratings by the expert judges than did the control compositions. These results provide evidence for the effectiveness of mental imagery in enhancing young children’s music compositional creativity. PMID:28296965

  19. Evolution of Outer Retinal Folds Occurring after Vitrectomy for Retinal Detachment Repair

    NARCIS (Netherlands)

    Dell'Omo, Roberto; Tan, H. Stevie; Schlingemann, Reinier O.; Bijl, Heico M.; Lesnik Oberstein, Sarit Y.; Barca, Francesco; Mura, Marco

    2012-01-01

    PURPOSE. To assess the evolution of outer retinal folds (ORFs) occurring after repair of rhegmatogenous retinal detachment (RRD) using spectral domain-optical coherence tomography (sd-OCT) and fundus autofluorescence (FAF), and to discuss their pathogenesis. METHODS. Twenty patients were operated on

  20. Protein kinase C in porcine retinal arteries and neuroretina following retinal ischemia-reperfusion

    DEFF Research Database (Denmark)

    Gesslein, Bodil; Gustafsson, Lotta; Wackenfors, Angelica

    2009-01-01

    Identification of the intracellular signal-transduction pathways activated in retinal ischemia may be important in revealing novel pharmacological targets. To date, most studies have focused on identifying neuroprotective agents. The retinal blood vessels are key organs in circulatory failure, an...