From retinal waves to activity-dependent retinogeniculate map development.

Science.gov (United States)

Markowitz, Jeffrey; Cao, Yongqiang; Grossberg, Stephen

2012-01-01

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

Development of a Guinea Pig Lung Deposition Model

Science.gov (United States)

2016-01-01

Development of a Guinea Pig Lung Deposition Model Distribution Statement A. Approved for public release; distribution is unlimited. January...4 Figure 2. Particle deposition in the lung of the guinea pig via endotracheal breathing...Particle deposition in the lungs of guinea pigs via nasal breathing. ......................................... 12 v PREFACE The research work

From retinal waves to activity-dependent retinogeniculate map development.

Directory of Open Access Journals (Sweden)

Jeffrey Markowitz

Full Text Available A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+-activated K(+ channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

Multifocal electroretinogram for functional evaluation of retinal injury following ischemia-reperfusion in pigs

DEFF Research Database (Denmark)

Morén, Håkan; Gesslein, Bodil; Andreasson, Sten

2010-01-01

Multifocal electroretinogram (mfERG) has the power to discriminate between localized functional losses and overall retinal changes when evaluating retinal injury. So far, full-field ERG has been the gold standard for examining retinal ischemia and the effects of different neuroprotectants...... in experimental conditions. The aim of the present study was to establish mfERG, with simultaneous fundus monitoring, for analyzing the localized functional response in the retina after ischemia-reperfusion in the porcine eye....

OCT as a convenient tool to assess the quality and application of organotypic retinal samples

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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.

Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

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Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke

2011-01-01

To investigate the feasibility of transplanting human neural progenitor cells (hNPCs) to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal ve...... that modulation of host immunity is likely necessary for prolonged xenograft survival in this model....

Peripheral retinal degenerations and the risk of retinal detachment.

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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.

Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

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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.

NUTRITION AND VASCULAR SUPPLY OF RETINAL GANGLION CELLS DURING HUMAN DEVELOPMENT

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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.

Leakage of colon anastomoses: development of an experimental model in pigs

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Nordentoft, Tyge; Sørensen, Michael

2007-01-01

model has only been developed in one gastric bypass study. The aim of the present study was to develop a leakage model of pig colon anastomoses. This type of study has never been performed before. Materials and Methods: Anastomosis was performed in 22 pigs. In all anastomoses a standardized rupture......: A model of anastomotic leakage on pig colon is developed with creation of a 21-mm rupture in the anastomotic line....

Imaging retinal progenitor lineages in developing zebrafish embryos.

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Jusuf, Patricia; Harris, William A; Poggi, Lucia

2013-03-01

In this protocol, we describe how to make and analyze four dimensional (4D) movies of retinal lineage in the zebrafish embryo in vivo. 4D consists of three spatial dimensions (3D) reconstructed from stacks of confocal planes plus one time dimension. Our imaging is performed on transgenic cells that express fluorescent proteins under the control of cell-specific promoters or on cells that transiently express such reporters in specific retinal cell progenitors. An important aspect of lineage tracing is the ability to follow individual cells as they undergo multiple cell divisions, final migration, and differentiation. This may mean many hours of 4D imaging, requiring that cells be kept healthy and maintained under conditions suitable for normal development. The longest movies we have made are ∼50 h. By analyzing these movies, we can see when a specific cell was born and who its sister was, allowing us to reconstruct its retinal lineages in vivo.

Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature.

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Luhmann, Ulrich F O; Lin, Jihong; Acar, Niyazi; Lammel, Stefanie; Feil, Silke; Grimm, Christian; Seeliger, Mathias W; Hammes, Hans-Peter; Berger, Wolfgang

2005-09-01

To characterize developmental defects and the time course of Norrie disease in retinal and hyaloid vasculature during retinal development and to identify underlying molecular angiogenic pathways that may be affected in Norrie disease, exudative vitreoretinopathy, retinopathy of prematurity, and Coats' disease. Norrie disease pseudoglioma homologue (Ndph)-knockout mice were studied during retinal development at early postnatal (p) stages (p5, p10, p15, and p21). Histologic techniques, quantitative RT-PCR, ELISA, and Western blot analyses provided molecular data, and scanning laser ophthalmoscopy (SLO) angiography and electroretinography (ERG) were used to obtain in vivo data. The data showed that regression of the hyaloid vasculature of Ndph-knockout mice occurred but was drastically delayed. The development of the superficial retinal vasculature was strongly delayed, whereas the deep retinal vasculature did not form because of the blockage of vessel outgrowth into the deep retinal layers. Subsequently, microaneurysm-like lesions formed. Several angiogenic factors were differentially transcribed during retinal development. Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse. These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks. They also suggest an early and a late phase of Norrie disease and may provide an explanation for similar phenotypic features of allelic retinal diseases in mice and patients as secondary consequences of pathologic hypoxia.

Effects of Constant Flickering Light on Refractive Status, 5-HT and 5-HT2A Receptor in Guinea Pigs.

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Li, Bing; Luo, Xiumei; Li, Tao; Zheng, Changyue; Ji, Shunmei; Ma, Yuanyuan; Zhang, Shuangshuang; Zhou, Xiaodong

2016-01-01

To investigate the effects of constant flickering light on refractive development, the role of serotonin (i.e.5-hydroxytryptamine, 5-HT)and 5-HT2A receptor in myopia induced by flickering light in guinea pigs. Forty-five guinea pigs were randomly divided into three groups: control, form deprivation myopia (FDM) and flickering light induced myopia (FLM) groups(n = 15 for each group). The right eyes of the FDM group were covered with semitransparent hemispherical plastic shells serving as eye diffusers. Guinea pigs in FLM group were raised with illumination of a duty cycle of 50% at a flash frequency of 0.5Hz. The refractive status, axial length (AL), corneal radius of curvature(CRC) were measured by streak retinoscope, A-scan ultrasonography and keratometer, respectively. Ultramicroscopy images were taken by electron microscopy. The concentrations of 5-HTin the retina, vitreous body and retinal pigment epithelium (RPE) were assessed by high performance liquid chromatography, the retinal 5-HT2A receptor expression was evaluated by immunohistofluorescence and western blot. The refraction of FDM and FLM eyes became myopic from some time point (the 4th week and the 6th week, respectively) in the course of the experiment, which was indicated by significantly decreased refraction and longer AL when compared with the controls (plight could cause progressive myopia in guinea pigs. 5-HT and 5-HT2A receptor increased both in form deprivation myopia and flickering light induced myopia, indicating that 5-HT possibly involved in myopic development via binding to5-HT2A receptor.

Incremental retinal-defocus theory of myopia development--schematic analysis and computer simulation.

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Hung, George K; Ciuffreda, Kenneth J

2007-07-01

Previous theories of myopia development involved subtle and complex processes such as the sensing and analyzing of chromatic aberration, spherical aberration, spatial gradient of blur, or spatial frequency content of the retinal image, but they have not been able to explain satisfactorily the diverse experimental results reported in the literature. On the other hand, our newly proposed incremental retinal-defocus theory (IRDT) has been able to explain all of these results. This theory is based on a relatively simple and direct mechanism for the regulation of ocular growth. It states that a time-averaged decrease in retinal-image defocus area decreases the rate of release of retinal neuromodulators, which decreases the rate of retinal proteoglycan synthesis with an associated decrease in scleral structural integrity. This increases the rate of scleral growth, and in turn the eye's axial length, which leads to myopia. Our schematic analysis has provided a clear explanation for the eye's ability to grow in the appropriate direction under a wide range of experimental conditions. In addition, the theory has been able to explain how repeated cycles of nearwork-induced transient myopia leads to repeated periods of decreased retinal-image defocus, whose cumulative effect over an extended period of time results in an increase in axial growth that leads to permanent myopia. Thus, this unifying theory forms the basis for understanding the underlying retinal and scleral mechanisms of myopia development.

Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.

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Townes-Anderson, Ellen; Wang, Jianfeng; Halász, Éva; Sugino, Ilene; Pitler, Amy; Whitehead, Ian; Zarbin, Marco

2017-06-01

Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM). In some animals, fasudil was injected intravitreally after BSS-induced detachment. After 2 to 4 hours, retinae were fixed for immunocytochemistry and confocal microscopy. Axon retraction was quantified by imaging synaptic vesicle label in the outer nuclear layer. Apoptosis was analyzed using propidium iodide staining. For biochemical analysis by Western blotting, retinal explants, detached from retinal pigmented epithelium, were cultured for 2 hours. Subretinal injection of fasudil (10 mM) reduced retraction of rod spherules by 51.3% compared to control detachments ( n = 3 pigs, P = 0.002). Intravitreal injection of 10 mM fasudil, a more clinically feasible route of administration, also reduced retraction (28.7%, n = 5, P ROCK, was decreased with 30 μM fasudil ( n = 8-10 explants, P ROCK signaling with fasudil reduced photoreceptor degeneration and preserved the rod-bipolar synapse after retinal detachment. These results support the possibility, previously tested with Y27632, that ROCK inhibition may attenuate synaptic damage in iatrogenic detachments.

Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption.

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Michelle Lajko

Full Text Available Bronchopulmonary dysplasia (BPD is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR, shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P0 to P14 to model BPD, then allowed to recover in room air for 1 (P15, 7 (P21, or 14 days (P28. We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80 and lymphocytes (CD45R. Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.

Focal retinal phlebitis.

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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.

Changes in the gut microbiota of cloned and non-cloned control pigs during development of obesity: gut microbiota during development of obesity in cloned pigs.

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Pedersen, Rebecca; Andersen, Anders Daniel; Mølbak, Lars; Stagsted, Jan; Boye, Mette

2013-02-07

Obesity induced by a high-caloric diet has previously been associated with changes in the gut microbiota in mice and in humans. In this study, pigs were cloned to minimize genetic and biological variation among the animals with the aim of developing a controlled metabolomic model suitable for a diet-intervention study. Cloning of pigs may be an attractive way to reduce genetic influences when investigating the effect of diet and obesity on different physiological sites. The aim of this study was to assess and compare the changes in the composition of the gut microbiota of cloned vs. non-cloned pigs during development of obesity by a high-fat/high-caloric diet. Furthermore, we investigated the association between diet-induced obesity and the relative abundance of the phyla Firmicutes and Bacteroidetes in the fecal-microbiota. The fecal microbiota from obese cloned (n = 5) and non-cloned control pigs (n= 6) was investigated biweekly over a period of 136 days, by terminal restriction fragment length polymorphism (T-RFLP) and quantitative real time PCR (qPCR). A positive correlation was observed between body-weight at endpoint and percent body-fat in cloned (r=0.9, Pmicrobiota between the cloned pigs or between cloned and non-cloned control pigs. Body-weight correlated positively with the relative abundance of Firmicutes in both cloned (r=0.37; Pgut microbiota in neither the obese nor the lean state. Diet-induced obesity was associated with an increase in the relative abundance of Firmicutes over time. Our results suggest that cloned pigs are not a more suitable animal model for gut microbiota-obesity related studies than non-cloned pigs. This study is the first to evaluate if cloned pigs provide a better animal model than conventional pigs in diet-intervention, obesity and gut microbiota research.

Effects of 530 nm green light on refractive status, melatonin, MT1 receptor, and melanopsin in the guinea pig.

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Wang, Fei; Zhou, Jiaqi; Lu, Yi; Chu, Renyuan

2011-02-01

To investigate (i) the effect of monochromatic light on inhibiting induction of light-induced melatonin and (ii) the roles of melanopsin and MT1 receptor in light-induced myopia in the guinea pig. Forty-eight guinea pigs were randomly distributed into three treatment groups: white-light (control), green-light (530 nm), and blue-light (480 nm) groups. Levels of pineal gland melatonin were measured twice daily--10:00 a.m. and 10:00 p.m.--10 days after initial light treatment. Thirty additional guinea pigs were also assigned to these groups and treated similarly. For these latter animals, refractive status, ocular length, and vitreous depth were measured before and after light treatment. Eight weeks after light treatment, retinal and sceral levels of melanopsin, melatonin receptor type (MT) 1, and mRNA protein were determined by Western blotting, real-time polymerase chain reaction (RT-PCR), and immunohistochemistry. The level of pineal gland melatonin in the green-light group was significantly higher than that in the blue-light group. Biometric measurements showed that guinea pigs in the green-light group had a somewhat myopic refractive status. Expressions of retinal melanopsin mRNA and protein were significantly higher in the blue-light group and lower in the green-light group when compared to controls. Conversely, expressions of MT1 receptor mRNA and protein in retina and sclera were significantly higher in the green-light group and lower in the blue-light group when compared to controls. Green light appears to suppress induction of melatonin production. In addition, 530 nm of green light is involved in the development of myopia. In the guinea pig, MT1 receptor and melanopsin appear to play roles in the development of myopia induced by 530 nm of light.

The effect of EGb 761 on retinal lipid peroxidation and glutathione peroxidase level in experimental lens induced uveitis.

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Bilgihan, A; Aricioğlu, A; Bilgihan, K; Onol, M; Hasanreisoğlu, B; Türközkan, N

1994-01-01

An acute lens-induced necrotizing intraocular inflammation was produced in pigmented guinea pigs. Treatment of these animals by 100 mg/kg/day EGb 761 a free oxygen radical scavenger for 10 days, reduced retinal lipid peroxidation (p > 0.05) and increased the retinal glutathione peroxidase level (p > 0.05). Although not significantly, these findings suggest that EGb 761 could be combined with other antiinflammatory drugs and may be beneficial in the treatment of uveitis.

Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity.

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Hong, Hye Kyoung; Lee, Hyun Ju; Ko, Jung Hwa; Park, Ji Hyun; Park, Ji Yeon; Choi, Chang Won; Yoon, Chang-Hwan; Ahn, Seong Joon; Park, Kyu Hyung; Woo, Se Joon; Oh, Joo Youn

2014-05-15

Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats. To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis. We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located. Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.

Raised intraocular pressure and recurrence of retinal detachment as complications of external retinal detachment surgery

International Nuclear Information System (INIS)

Jawwad, M.; Khan, B.; Shah, M.A.; Qayyum, I.; Aftab, M.; Qayyum, I.

2015-01-01

Patients with Rhegmatogenous retinal detachment may develop raised intraocular pressure and recurrence of retinal detachment when they undergo external retinal detachment surgery. The present study was conducted to determine the postoperative rise in intraocular pressure (IOP) and recurrence of retinal detachment. Methods: The present descriptive study was conducted at Eye department of Lady Reading Hospital, Peshawar on 25 patients of both genders from August 2012 to July 2014. Results: Of the 25 patients, 18 (72%) developed raised IOP in the immediate postoperative period; this figure decreased to 12 (48%) at one week. Following medical or surgical intervention in these 12 cases, there was only 1 (4%) case with mildly raised IOP at two weeks postoperative. Five (20%) cases developed recurrent retinal detachment which later resolved with treatment. There were no significant differences by age or gender. Conclusion: External Retinal Detachment Surgery raised intraocular pressure postoperatively and caused recurrence of retinal detachment. These complications were treated medically and surgically with resolution within two weeks. (author)

Efeito do ácido trans-retinóico na inibição de colesteatoma em cobaias Effect of trans-retinoic acid in the inhibition of cholesteatoma in guinea pigs

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Marcos Luiz Antunes

2008-02-01

Full Text Available O colesteatoma de orelha média atingia mais de 5 milhões de pessoas até a década de 80. Vários modelos animais já foram utilizados para alternativas de tratamento do colesteatoma sem sucesso. OBJETIVO: Estudar os efeitos do ácido trans-retinóico, uso tópico na orelha externa em cobaias, na inibição da formação do colesteatoma de orelha média induzido pelo propilenoglicol. Estudo experimental prospectivo. MATERIAL E MÉTODOS: 25 cobaias foram submetidas à aplicação de propilenoglicol a 100% na bula timpânica bilateralmente e uma solução de ácido trans-retinóico foi aplicada topicamente (total de 5 aplicações na orelha externa, região justa-timpânica, na orelha direita, enquanto na orelha esquerda aplicou-se solução fisiológica (orelha controle. As cobaias foram sacrificadas após 6 semanas do procedimento inicial e os ossos temporais foram separados, fixados e descalcificados, para análise macroscópica e histológica. RESULTADOS: Os achados macroscópicos evidenciaram a presença e suspeita de colesteatoma em 25% das orelhas direitas e 85% das orelhas esquerdas (P=0,0003*. Os achados histológicos dos 40 ossos temporais evidenciaram a presença de colesteatoma em 30% das orelhas direitas e 75% das orelhas esquerdas (P=0,0104*. CONCLUSÃO: O uso tópico do ácido trans-retinóico é efetivo na inibição da formação de colesteatoma induzido pelo propilenoglicol em cobaias.Middle ear cholesteatoma affected more than 5 million people until the 80`s. Many animal models were used, unsuccessfully, to study an alternative therapy to cholesteatoma. AIM: observe the effect of the trans-retinoic acid in the inhibition of middle ear cholesteatomas induced by propylene glycol. STUDY DESIGN: Clinical and Experimental. METHODS: 25 guinea pigs were submitted to the application of a 100% propylene glycol solution in their bulla bilaterally and a solution of trans-retinoic acid was applied locally in the external right ear, while

[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.

Retinal detachment and retinal holes in retinitis pigmentosa sine pigmento.

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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.

Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa.

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Miao Chen

Full Text Available Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP in one subset of cone bipolar cells (type 7 into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of cone bipolar cells in a background of retinal degeneration. Our data revealed that both the development and degeneration of cone bipolar cells are independent of the normal activity of cone photoreceptors. We found that type 7 cone bipolar cells achieved a uniform tiling of the retinal surface and developed normal dendritic and axonal arbors without the influence of cone photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar cells, contrary to our belief of central-to-peripheral progression, was spatially uniform across the retina independent of the spatiotemporal pattern of cone degeneration. The results have important implications for the design of more effective therapies to restore vision in retinal degeneration.

Giant Retinal Tear With Retinal Detachment in Regressed Aggressive Posterior Retinopathy of Prematurity Treated by Laser.

Science.gov (United States)

Chandra, Parijat; Tewari, Ruchir; Salunkhe, Nitesh; Kumawat, Devesh; Kumar, Vinod

2017-06-29

Rhegmatogenous retinal detachment after successfully regressed retinopathy of prematurity is a rare occurrence. Late onset rhegmatogenous retinal detachment has been reported infrequently. The authors report a case of aggressive posterior retinopathy of prematurity that underwent uneventful regression after laser photocoagulation and later developed an inoperable closed funnel retinal detachment due to a giant retinal tear. This case represents the earliest development of such complications in regressed aggressive posterior retinopathy of prematurity treated by laser. Development of a giant retinal tear has also not been previously reported after laser treatment. This case highlights that successful regression of severe retinopathy of prematurity does not safeguard against future complications and requires frequent long-term follow-up. [J Pediatr Ophthalmol Strabismus. 2017;54:e34-e36.]. Copyright 2017, SLACK Incorporated.

Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: Beneficial effects of the LpPLA2 inhibitor Darapladib.

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Acharya, Nimish K; Qi, Xin; Goldwaser, Eric L; Godsey, George A; Wu, Hao; Kosciuk, Mary C; Freeman, Theresa A; Macphee, Colin H; Wilensky, Robert L; Venkataraman, Venkat; Nagele, Robert G

2017-05-01

Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta 1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib. These findings suggest that chronic diabetes mellitus and hypercholesterolaemia induces increased blood-retina barrier permeability that may be linked to altered expression of blood-retina barrier-associated tight junction proteins, claudin and occludin, leading to structural changes in the retina consistent with diabetic retinopathy. Additionally, results suggest that drugs with vascular anti-inflammatory properties, such as Darapladib, may have beneficial effects on eye diseases strongly linked to vascular abnormalities such as diabetic retinopathy and age-related macular degeneration.

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...

Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

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Yuta Inokuchi

2006-01-01

Full Text Available Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retina in vitro and/or in vivo. In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2 exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation, as also did trolox (water-soluble vitamin E. In mice in vivo, propolis (100 mg kg−1; intraperitoneally administered four times reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer induced by intravitreal in vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage both in vitro and in vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

Missed retinal breaks in rhegmatogenous retinal detachment

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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.

Changes in the gut microbiota of cloned and non-cloned control pigs during development of obesity: gut microbiota during development of obesity in cloned pigs

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Pedersen, Rebecca; Andersen, Anders Daniel; Mølbak, Lars

2013-01-01

Background Obesity induced by a high-caloric diet has previously been associated with changes in the gut microbiota in mice and in humans. In this study, pigs were cloned to minimize genetic and biological variation among the animals with the aim of developing a controlled metabolomic model...... suitable for a diet-intervention study. Cloning of pigs may be an attractive way to reduce genetic influences when investigating the effect of diet and obesity on different physiological sites. The aim of this study was to assess and compare the changes in the composition of the gut microbiota of cloned vs....... non-cloned pigs during development of obesity by a high-fat/high-caloric diet. Furthermore, we investigated the association between diet-induced obesity and the relative abundance of the phyla Firmicutes and Bacteroidetes in the fecal-microbiota. The fecal microbiota from obese cloned (n = 5) and non...

Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

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Huang, Wenhu, E-mail: wenhu.huang@pfizer.com; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

2015-12-15

Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

International Nuclear Information System (INIS)

Huang, Wenhu; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

2015-01-01

Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

A hybrid discrete-continuum mathematical model of pattern prediction in the developing retinal vasculature.

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McDougall, S R; Watson, M G; Devlin, A H; Mitchell, C A; Chaplain, M A J

2012-10-01

Pathological angiogenesis has been extensively explored by the mathematical modelling community over the past few decades, specifically in the contexts of tumour-induced vascularisation and wound healing. However, there have been relatively few attempts to model angiogenesis associated with normal development, despite the availability of animal models with experimentally accessible and highly ordered vascular topologies: for example, growth and development of the vascular plexus layers in the murine retina. The current study aims to address this issue through the development of a hybrid discrete-continuum mathematical model of the developing retinal vasculature in neonatal mice that is closely coupled with an ongoing experimental programme. The model of the functional vasculature is informed by a range of morphological and molecular data obtained over a period of several days, from 6 days prior to birth to approximately 8 days after birth. The spatio-temporal formation of the superficial retinal vascular plexus (RVP) in wild-type mice occurs in a well-defined sequence. Prior to birth, astrocytes migrate from the optic nerve over the surface of the inner retina in response to a chemotactic gradient of PDGF-A, formed at an earlier stage by migrating retinal ganglion cells (RGCs). Astrocytes express a variety of chemotactic and haptotactic proteins, including VEGF and fibronectin (respectively), which subsequently induce endothelial cell sprouting and modulate growth of the RVP. The developing RVP is not an inert structure; however, the vascular bed adapts and remodels in response to a wide variety of metabolic and biomolecular stimuli. The main focus of this investigation is to understand how these interacting cellular, molecular, and metabolic cues regulate RVP growth and formation. In an earlier one-dimensional continuum model of astrocyte and endothelial migration, we showed that the measured frontal velocities of the two cell types could be accurately reproduced

Development of pig welfare assessment protocol integrating animal-, environment-, and management-based measures.

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Renggaman, Anriansyah; Choi, Hong L; Sudiarto, Sartika Ia; Alasaarela, Laura; Nam, Ok S

2015-01-01

Due to increased interest in animal welfare, there is now a need for a comprehensive assessment protocol to be used in intensive pig farming systems. There are two current welfare assessment protocols for pigs: Welfare Quality® Assessment Protocols (applicable in the Europe Union), that mostly focuses on animal-based measures, and the Swine Welfare Assurance Program (applicable in the United States), that mostly focuses on management- and environment-based measures. In certain cases, however, animal-based measures might not be adequate for properly assessing pig welfare status. Similarly, welfare assessment that relies only on environment- and management-based measures might not represent the actual welfare status of pigs. Therefore, the objective of this paper was to develop a new welfare protocol by integrating animal-, environment-, and management-based measures. The background for selection of certain welfare criteria and modification of the scoring systems from existing welfare assessment protocols are described. The developed pig welfare assessment protocol consists of 17 criteria that are related to four main principles of welfare (good feeding, good housing, good health, and appropriate behavior). Good feeding, good housing, and good health were assessed using a 3-point scale: 0 (good welfare), 1 (moderate welfare), and 2 (poor welfare). In certain cases, only a 2-point scale was used: 0 (certain condition is present) or 2 (certain condition is absent). Appropriate behavior was assessed by scan sampling of positive and negative social behaviors based on qualitative behavior assessment and human-animal relationship tests. Modification of the body condition score into a 3-point scale revealed pigs with a moderate body condition (score 1). Moreover, additional criteria such as feed quality confirmed that farms had moderate (score 1) or poor feed quality (score 2), especially those farms located in a high relative humidity region. The developed protocol can be

External Genital Development, Urethra Formation, and Hypospadias Induction in Guinea Pig: A Double Zipper Model for Human Urethral Development.

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Wang, Shanshan; Shi, Mingxin; Zhu, Dongqing; Mathews, Ranjiv; Zheng, Zhengui

2018-03-01

To determine whether the guinea pig phallus would be an appropriate model of human penile development, we characterized the embryology and sexual differentiation of guinea pig external genitalia and attended to induce hypospadias in males and tubular urethra formation in females pharmacologically. The external genitalia of guinea pig were collected from genital swelling initiation to newborn stages, and scanning electronic microscopy and histology were performed to visualize the morphology and structure. Immunohistochemistry was used to determine the androgen receptor localization. Bicalutamide and methyltestosterone were given to pregnant dams to reveal the role and timing of androgen in guinea pig penile masculinization. Canalization and dorsal-to-ventral movement of the urethral canal develops the urethral groove in both sexes, and then the males perform distal-opening-proximal-closing to form tubular urethra. More nuclear-localized androgen receptor is found in proximal genital tubercles of males than in females at (E) 29. Antiandrogen treatment at E26-E30 can cause hypospadias, and methyltestosterone administration at E27-E31 can induce tubular urethra formation in females. Fetal development of the guinea pig phallus is homologous to that of humans. Although guinea pig has structures similar to mouse, the urethral groove and the tubular urethra formation are more similar to humans. Antiandrogen treatment causes hypospadias in males and additional androgen induces tubular urethra formation in females. Thus, guinea pig is an appropriate model for further study of cellular and molecular mechanisms involved in distal-opening-proximal-closing in tubular urethra formation and the evaluation of the pathophysiological processes of hypospadias. Published by Elsevier Inc.

Fluorescein angiography and retinal vascular development in premature infants.

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Purcaro, Velia; Velia, Purcaro; Baldascino, Antonio; Antonio, Baldascino; Papacci, Patrizia; Patrizia, Papacci; Giannantonio, Carmen; Carmen, Giannantonio; Molisso, Anna; Anna, Molisso; Molle, Fernando; Fernando, Molle; Lepore, Domenico; Domenico, Lepore; Romagnoli, Costantino; Costantino, Romagnoli

2012-10-01

To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.

Retinal detachment following endophthalmitis.

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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.

Development of a radioimmunoassay for pig pancreatic kallikrein and its application in physiological studies

International Nuclear Information System (INIS)

Fink, E.; Guettel, C.; Seifert, J.

1978-01-01

A RIA for pig pancreatic kallikrein has been developed. Purified kallikrein was labelled with 125 I. The use of radioimmunoassays in investigating the intestinal absorption of pig pancreas kallikrein is dealt with. (VJ) [de

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment

Science.gov (United States)

Lee, Christine; Tu, Hong Anh; Weir, Mark; Holubowich, Corinne

2016-01-01

Background Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. Methods We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients’ lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. Results One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life

Retinal Vessels Segmentation Techniques and Algorithms: A Survey

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Jasem Almotiri

2018-01-01

Full Text Available Retinal vessels identification and localization aim to separate the different retinal vasculature structure tissues, either wide or narrow ones, from the fundus image background and other retinal anatomical structures such as optic disc, macula, and abnormal lesions. Retinal vessels identification studies are attracting more and more attention in recent years due to non-invasive fundus imaging and the crucial information contained in vasculature structure which is helpful for the detection and diagnosis of a variety of retinal pathologies included but not limited to: Diabetic Retinopathy (DR, glaucoma, hypertension, and Age-related Macular Degeneration (AMD. With the development of almost two decades, the innovative approaches applying computer-aided techniques for segmenting retinal vessels are becoming more and more crucial and coming closer to routine clinical applications. The purpose of this paper is to provide a comprehensive overview for retinal vessels segmentation techniques. Firstly, a brief introduction to retinal fundus photography and imaging modalities of retinal images is given. Then, the preprocessing operations and the state of the art methods of retinal vessels identification are introduced. Moreover, the evaluation and validation of the results of retinal vessels segmentation are discussed. Finally, an objective assessment is presented and future developments and trends are addressed for retinal vessels identification techniques.

A novel transgenic zebrafish model for blood-brain and blood-retinal barrier development

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Sugimoto Masahiko

2010-07-01

Full Text Available Abstract Background Development and maintenance of the blood-brain and blood-retinal barrier is critical for the homeostasis of brain and retinal tissue. Despite decades of research our knowledge of the formation and maintenance of the blood-brain (BBB and blood-retinal (BRB barrier is very limited. We have established an in vivo model to study the development and maintenance of these barriers by generating a transgenic zebrafish line that expresses a vitamin D-binding protein fused with enhanced green fluorescent protein (DBP-EGFP in blood plasma, as an endogenous tracer. Results The temporal establishment of the BBB and BRB was examined using this transgenic line and the results were compared with that obtained by injection of fluorescent dyes into the sinus venosus of embryos at various stages of development. We also examined the expression of claudin-5, a component of tight junctions during the first 4 days of development. We observed that the BBB of zebrafish starts to develop by 3 dpf, with expression of claudin-5 in the central arteries preceding it at 2 dpf. The hyaloid vasculature in the zebrafish retina develops a barrier function at 3 dpf, which endows the zebrafish with unique advantages for studying the BRB. Conclusion Zebrafish embryos develop BBB and BRB function simultaneously by 3 dpf, which is regulated by tight junction proteins. The Tg(l-fabp:DBP-EGFP zebrafish will have great advantages in studying development and maintenance of the blood-neural barrier, which is a new application for the widely used vertebrate model.

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

The Pig PeptideAtlas

DEFF Research Database (Denmark)

Hesselager, Marianne Overgaard; Codrea, Marius; Sun, Zhi

2016-01-01

Biological research of Sus scrofa, the domestic pig, is of immediate relevance for food production sciences, and for developing pig as a model organism for human biomedical research. Publicly available data repositories play a fundamental role for all biological sciences, and protein data...... repositories are in particular essential for the successful development of new proteomic methods. Cumulative proteome data repositories, including the PeptideAtlas, provide the means for targeted proteomics, system-wide observations, and cross-species observational studies, but pigs have so far been...... underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within...

Establishing the pig as a large animal model for vaccine development against human cancer

DEFF Research Database (Denmark)

Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

2015-01-01

Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer....

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

Science.gov (United States)

Pavesio, C E; Mitchell, S M; Barton, K; Schwartz, S D; Towler, H M; Lightman, S

1995-01-01

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

Developing guinea pig brain as a model for cortical folding.

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Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

2017-05-01

The cerebral cortex in mammals, the neocortex specifically, is highly diverse among species with respect to its size and morphology, likely reflecting the immense adaptiveness of this lineage. In particular, the pattern and number of convoluted ridges and fissures, called gyri and sulci, respectively, on the surface of the cortex are variable among species and even individuals. However, little is known about the mechanism of cortical folding, although there have been several hypotheses proposed. Recent studies on embryonic neurogenesis revealed the differences in cortical progenitors as a critical factor of the process of gyrification. Here, we investigated the gyrification processes using developing guinea pig brains that form a simple but fundamental pattern of gyri. In addition, we established an electroporation-mediated gene transfer method for guinea pig embryos. We introduce the guinea pig brain as a useful model system to understand the mechanisms and basic principle of cortical folding. © 2017 Japanese Society of Developmental Biologists.

Lipofection strategy for the study of Xenopus retinal development.

Science.gov (United States)

Ohnuma, Shin-ichi; Mann, Fanny; Boy, Sébastien; Perron, Muriel; Harris, William A

2002-12-01

The analysis of gene function during retinal development can be addressed by perturbing gene expression either by inhibition or by overexpression in desired regions and at defined stages of development. An in vivo lipofection strategy has been applied for stage-specific and region-specific expression of genes in Xenopus retina. Due to colipofection efficiency, this strategy enables us to study functional interaction of genes by lipofecting multiple expression constructs. This lipofection technique also allows us to transfect morpholino oligonucleotides into retinoblasts to block gene function. We present here various aspects of this technique, including recent improvements and modifications.

Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats.

Science.gov (United States)

Kiss, Peter; Szogyi, Donat; Reglodi, Dora; Horvath, Gabor; Farkas, Jozsef; Lubics, Andrea; Tamas, Andrea; Atlasz, Tamas; Szabadfi, Krisztina; Babai, Norbert; Gabriel, Robert; Koppan, Miklos

2009-02-19

Perinatal asphyxia during delivery produces long-term deficits and represents a major problem in both neonatal and pediatric care. Several morphological, biochemical and behavioral changes have been described in rats exposed to perinatal asphyxia. The aim of the present study was to evaluate how perinatal asphyxia affects the complex early neurobehavioral development and retinal structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by cesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily during the first 3 weeks, and motor coordination tests were performed on postnatal weeks 3-5. After completion of the testing procedure, retinas were removed for histological analysis. We found that in spite of the fast catch-up-growth of asphyctic pups, nearly all examined reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting reflexes, development of fore- and hindlimb grasp and placing, gait and auditory startle reflexes. Time to perform negative geotaxis, surface righting and gait reflexes was significantly longer during the first few weeks in asphyctic pups. Among the motor coordination tests, a markedly weaker performance was observed in the grid walking and footfault test and in the walk initiation test. Retinal structure showed severe degeneration in the layer of the photoreceptor and bipolar cell bodies. In summary, our present study provided a detailed description of reflex and motor development following perinatal asphyxia, showing that asphyxia led to a marked delay in neurobehavioral development and a severe retinal degeneration.

Status of Taenia solium cysticercosis and predisposing factors in developing countries involved in pig farming

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Joseph M. Kungu

2015-05-01

Full Text Available Taenia solium cysticercosis is a disease of pigs and humans populations considered endemic in many developing countries of Latin America, Africa, and South East Asia having serious impact on public health and agriculture. We conducted an in-depth comparative analysis of literature on the disease situation and predisposing factors in selected countries known to be at the interface of poverty-emerging livestock systems-zoonoses and with a growing small holder pig industry. Transmission, methods of diagnosis and employed control strategies of T. solium infection in pig and human populations in these countries are also discussed. Limited knowledge on porcine cysticercosis (PC by various stakeholders expected to be key players in its control has undermined efforts for eliminating this potentially eradicable condition. Poor pig production practices, poor hygiene, and sanitation habits have also been important in the maintenance of the T. solium life-cycle. The major gaps identified in this review include scanty current information on PC prevalence in pigs with hardly any reports on the condition in humans in most developing countries. Factors affecting pattern of the infection and how they interact at the different levels of the pig value chain have not been exhaustively studied. Information on socioeconomic and public health impact is inadequate and not current.

Retinal Cell Degeneration in Animal Models

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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.

Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig.

Science.gov (United States)

Wei, Lihua; Ge, Li; Qin, Shucun; Shi, Yunzhi; Du, Changqing; Du, Hui; Liu, Liwei; Yu, Yang; Sun, Xuejun

2012-01-01

Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Targeted disruption of CD1d prevents NKT cell development in pigs.

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Yang, Guan; Artiaga, Bianca L; Hackmann, Timothy J; Samuel, Melissa S; Walters, Eric M; Salek-Ardakani, Shahram; Driver, John P

2015-06-01

Studies in mice genetically lacking natural killer T (NKT) cells show that these lymphocytes make important contributions to both innate and adaptive immune responses. However, the usefulness of murine models to study human NKT cells is limited by the many differences between mice and humans, including that their NKT cell frequencies, subsets, and distribution are dissimilar. A more suitable model may be swine that share many metabolic, physiological, and growth characteristics with humans and are also similar for NKT cells. Thus, we analyzed genetically modified pigs made deficient for CD1d that is required for the development of Type I invariant NKT (iNKT) cells that express a semi-invariant T-cell receptor (TCR) and Type II NKT cells that use variable TCRs. Peripheral blood analyzed by flow cytometry and interferon-γ enzyme-linked immuno spot assays demonstrated that CD1d-knockout pigs completely lack iNKT cells, while other leukocyte populations remain intact. CD1d and NKT cells have been shown to be involved in shaping the composition of the commensal microbiota in mice. Therefore, we also compared the fecal microbiota profile between pigs expressing and lacking NKT cells. However, no differences were found between pigs lacking or expressing CD1d. Our results are the first to show that knocking-out CD1d prevents the development of NKT cells in a non-rodent species. CD1d-deficient pigs should offer a useful model to more accurately determine the contribution of NKT cells for human immune responses. They also have potential for understanding how NKT cells impact the health of commercial swine.

Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion

DEFF Research Database (Denmark)

Cehofski, Lasse Jørgensen; Kruse, Anders; Magnusdottir, Sigriður Olga

2018-01-01

while the left control eye was given an identical injection without an implant. Fifteen days after BRVO and DEX implant intervention the retinas were excised and analyzed with tandem mass tag based mass spectrometry. A total of 26 significantly changed proteins were identified. Dexamethasone...... following an intervention with a dexamethasone (DEX) implant this study combined an experimental model of BRVO with proteomic techniques. In six Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser. After inducing BRVO a DEX implant was injected in the right eye of each animal......-α and caveolin-1 were confirmed with immunohistochemistry. DEX implant intervention may inhibit PDGF signaling by decreasing the retinal level of PDGFR-α while an increased content of caveolin-1 may help maintain the integrity of the blood-retinal barrier....

Silver nano - a trove for retinal therapies.

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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.

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.

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...

Changes in guinea-pig dermal collagen during development

International Nuclear Information System (INIS)

Shuttleworth, C.A.; Forrest, L.

1975-01-01

Guinea-pig dermis was digested with pepsin and the solubilized collagen molecules separated by differential salt precipitation at pH 7.5. Differences in subunit composition and amino acid analysis were noted between type I and type III collagen. Incorporation of radioactive proline into the developing foetus enabled isolation of labelled type I and type III collagens. Comparison of the specific activity of the isolated collagen molecules showed that type III collagen had a high specific activity in the early stages of foetal development, which decreased dramatically during foetal development. The specific activity of pepsin-solubilized type I collagen remained fairly constant during foetal development. (orig.) [de

Progranulin deficiency causes the retinal ganglion cell loss during development.

Science.gov (United States)

Kuse, Yoshiki; Tsuruma, Kazuhiro; Mizoguchi, Takahiro; Shimazawa, Masamitsu; Hara, Hideaki

2017-05-10

Astrocytes are glial cells that support and protect neurons in the central nervous systems including the retina. Retinal ganglion cells (RGCs) are in contact with the astrocytes and our earlier findings showed the reduction of the number of cells in the ganglion cell layer in adult progranulin deficient mice. In the present study, we focused on the time of activation of the astrocytes and the alterations in the number of RGCs in the retina and optic nerve in progranulin deficient mice. Our findings showed that the number of Brn3a-positive cells was reduced and the expression of glial fibrillary acidic protein (GFAP) was increased in progranulin deficient mice. The progranulin deficient mice had a high expression of GFAP on postnatal day 9 (P9) but not on postnatal day 1. These mice also had a decrease in the number of the Brn3a-positive cells on P9. Taken together, these findings indicate that the absence of progranulin can affect the survival of RGCs subsequent the activation of astrocytes during retinal development.

Macrolides and lincosamides in cattle and pigs: use and development of antimicrobial resistance.

Science.gov (United States)

Pyörälä, Satu; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Greko, Christina; Moreno, Miguel A; Pomba, M Constança Matias Ferreira; Rantala, Merja; Ružauskas, Modestas; Sanders, Pascal; Threlfall, E John; Torren-Edo, Jordi; Törneke, Karolina

2014-05-01

Macrolides and lincosamides are important antibacterials for the treatment of many common infections in cattle and pigs. Products for in-feed medication with these compounds in combination with other antimicrobials are commonly used in Europe. Most recently approved injectable macrolides have very long elimination half-lives in both pigs and cattle, which allows once-only dosing regimens. Both in-feed medication and use of long-acting injections result in low concentrations of the active substance for prolonged periods, which causes concerns related to development of antimicrobial resistance. Acquired resistance to macrolides and lincosamides among food animal pathogens, including some zoonotic bacteria, has now emerged. A comparison of studies on the prevalence of resistance is difficult, since for many micro-organisms no agreed standards for susceptibility testing are available. With animal pathogens, the most dramatic increase in resistance has been seen in the genus Brachyspira. Resistance towards macrolides and lincosamides has also been detected in staphylococci isolated from pigs and streptococci from cattle. This article reviews the use of macrolides and lincosamides in cattle and pigs, as well as the development of resistance in target and some zoonotic pathogens. The focus of the review is on European conditions. Copyright © 2014. Published by Elsevier Ltd.

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

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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.

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.

Long non-coding RNAs and mRNAs profiling during spleen development in pig.

Science.gov (United States)

Che, Tiandong; Li, Diyan; Jin, Long; Fu, Yuhua; Liu, Yingkai; Liu, Pengliang; Wang, Yixin; Tang, Qianzi; Ma, Jideng; Wang, Xun; Jiang, Anan; Li, Xuewei; Li, Mingzhou

2018-01-01

Genome-wide transcriptomic studies in humans and mice have become extensive and mature. However, a comprehensive and systematic understanding of protein-coding genes and long non-coding RNAs (lncRNAs) expressed during pig spleen development has not been achieved. LncRNAs are known to participate in regulatory networks for an array of biological processes. Here, we constructed 18 RNA libraries from developing fetal pig spleen (55 days before birth), postnatal pig spleens (0, 30, 180 days and 2 years after birth), and the samples from the 2-year-old Wild Boar. A total of 15,040 lncRNA transcripts were identified among these samples. We found that the temporal expression pattern of lncRNAs was more restricted than observed for protein-coding genes. Time-series analysis showed two large modules for protein-coding genes and lncRNAs. The up-regulated module was enriched for genes related to immune and inflammatory function, while the down-regulated module was enriched for cell proliferation processes such as cell division and DNA replication. Co-expression networks indicated the functional relatedness between protein-coding genes and lncRNAs, which were enriched for similar functions over the series of time points examined. We identified numerous differentially expressed protein-coding genes and lncRNAs in all five developmental stages. Notably, ceruloplasmin precursor (CP), a protein-coding gene participating in antioxidant and iron transport processes, was differentially expressed in all stages. This study provides the first catalog of the developing pig spleen, and contributes to a fuller understanding of the molecular mechanisms underpinning mammalian spleen development.

Delayed development of systemic immunity in preterm pigs as a model for preterm infants

DEFF Research Database (Denmark)

Nguyen, Duc Ninh; Jiang, Pingping; Frøkiær, Hanne

2016-01-01

-mediated IL-6 and TNF-α production. These immune parameters remained different between preterm and near-term pigs at 2-3 weeks, even when adjusted for post-conceptional age. Our data suggest that systemic immunity follows a distinct developmental trajectory following preterm birth that may be influenced......Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life......, relative to those born at near-term or term. Using pigs as a model, we characterized blood leukocyte subsets, antimicrobial activities and TLR-mediated cytokine production during the first weeks after preterm birth. Relative to near-term and term pigs, newborn preterm pigs had low blood leukocyte counts...

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.

Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Science.gov (United States)

Twenhafel, N A; Shaia, C I; Bunton, T E; Shamblin, J D; Wollen, S E; Pitt, L M; Sizemore, D R; Ogg, M M; Johnston, S C

2015-01-01

Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. © The Author(s) 2014.

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.

Development of Pipe Inspection Gauge (PIG) for leak detection in buried pipelines using radiotracer technique

International Nuclear Information System (INIS)

Pendharkar, A.S.; Sharma, V.K.; Pant, H.J.; Singh, Gursharan

2004-01-01

This paper discusses the development of a portable battery operated radioisotope based pipeline inspection gauge( PIG) for detection and location of leaks as well as to examine the condition of the underground pipelines. The system consists of a scintillation detector, power supply for detector and other electronic circuits. Pulse processing amplifier data acquisition system, readout unit and software to transfer data to computer for further processing. The microcontroller based pig is very useful in a field in an underground pipeline of 6 inch diameter and above. The battery operated pig system developed indigenously is rugged and portable with data storage capacity up to 20 hours. The system was tested under simulated leak conditions and field trials are being planned. (author)

Activation of retinal stem cells in the proliferating marginal region of RCS rats during development of retinitis pigmentosa.

Science.gov (United States)

Jian, Qian; Xu, Haiwei; Xie, Hanping; Tian, Chunyu; Zhao, Tongtao; Yin, ZhengQin

2009-11-06

Retinal stem cells (RSCs) have been demonstrated at the proliferating marginal regions from the pars plana of ciliary body to the ciliary marginal zone (CMZ) in adult lower vertebrates and mammals. Investigations in the lower vertebrates have provided some evidence that RSCs can proliferate following retinal damage; however, the evidence that this occurs in mammals is not clear. In this study, we explored RSCs proliferation potential of adult mammalian in proliferating marginal regions of Royal College of Surgeons (RCS) rats, an animal model for retinitis pigmentosa (RP). The proliferation was evaluated using BrdU labeling, and Chx-10 as markers to discern progenitor cell of CMZ in Long-Evan's and RCS rats at different postnatal day (PND) after eye opening. We found that few Chx-10 and BrdU labeled cells in the proliferating marginal regions of Long-Evan's rats, which significantly increased in RCS rats at PND30 and PND60. Consistent with this, Chx-10/Vimentin double staining cells in the center retina of RCS rats increased significantly at PND30 after eye opening. In addition, mRNA expression of Shh, Ptch1 and Smo was up-regulated in RCS rats at PND60 compared to age-matched Long-Evan's rats, which revealed Shh/ptc pathway involving in the activation of RSCs. These results suggest that RSCs in the mammalian retinal proliferating marginal regions has the potential to regenerate following degeneration.

Recent developments in retinal lasers and delivery systems

Directory of Open Access Journals (Sweden)

Naresh Kumar Yadav

2014-01-01

Full Text Available Photocoagulation is the standard of care for several ocular disorders and in particular retinal conditions. Technology has offered us newer lasing mediums, wavelengths and delivery systems. Pattern scan laser in proliferative diabetic retinopathy and diabetic macular edema allows laser treatment that is less time consuming and less painful. Now, it is possible to deliver a subthreshold micropulse laser that is above the threshold of biochemical effect but below the threshold of a visible, destructive lesion thereby preventing collateral damage. The advent of solid-state diode yellow laser allows us to treat closer to the fovea, is more effective for vascular structures and offers a more uniform effect in patients with light or irregular fundus pigmentation. Newer retinal photocoagulation options along with their advantages is discussed in this review.

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.

Interventions for asymptomatic retinal breaks and lattice degeneration for preventing retinal detachment.

Science.gov (United States)

Wilkinson, Charles P

2014-09-05

Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these lesions frequently is recommended, in spite of the fact that the effectiveness of this therapy is unproven. The objective of this review was to assess the effectiveness and safety of techniques used to treat asymptomatic retinal breaks and lattice degeneration for the prevention of retinal detachment. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), PubMed (January 1948 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials

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.

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.

Feed- and feed additives-related aspects of gut health and development in weanling pigs.

Science.gov (United States)

Pluske, John R

2013-01-07

The development of new/different management and feeding strategies to stimulate gut development and health in newly-weaned pigs, in order to improve growth performance while minimizing the use of antimicrobial compounds such as antibiotic growth promotants (AGP) and heavy mineral compounds, is essential for the long-term sustainability of the pig industry. Factors including the sub-optimal intake of nutrients and energy, inappropriate microbiota biomass and (or) balance, immature and compromised immune function, and psychosomatic factors caused by weaning can compromise both the efficiency of digestion and absorption and intestinal barrier function through mucosal damage and alteration of tight junction integrity. As a consequence, pigs at weaning are highly susceptible to pathogenic enteric conditions such as post-weaning diarrhea that may be caused by serotypes of enterotoxigenic Escherichia coli. Many dietary components, e.g., protein, fiber, feed additives and minerals, are known to influence microbial growth in the gastrointestinal tract that in turn can impact upon pig growth and health, although the relationships between these are sometimes not necessarily apparent or obvious. In a world climate of increased scrutiny over the use of antibiotics per se in pig production, certain feed additives are seen as alternatives/replacements to antibiotics, and have evolved in some cases to have important roles in everyday commercial pig nutrition. Nevertheless and in general, there remains inconsistency and variability in the efficacy of some feed additives and in cases of severe disease outbreaks, for example, therapeutic antibiotics and/or heavy minerals such as zinc oxide (ZnO) are generally relied upon. If feed ingredients and (or) feed additives are to be used with greater regularity and reliability, then it is necessary to better understand the mechanisms whereby antibiotics and minerals such as ZnO influence animal physiology, in conjunction with the use of

Development of the micro-architecture and mineralization of the basilar part of the pig occipital bone

NARCIS (Netherlands)

Sips, R.J.A.; Mulder, L.; Koolstra, J.H.; Eijden, van T.M.G.J.

2008-01-01

In this study, the development of the architecture and the degree and distribution of mineralization in the basilar part of the pig occipital bone, one of the contact points between the spine and skull base, was investigated. Multiple regions of the basiocciput of pig specimens of different

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.

Risk of Retinal Detachment After Pediatric Cataract Surgery

DEFF Research Database (Denmark)

Haargaard, Birgitte; Andersen, Elisabeth W; Oudin, Anna

2014-01-01

PURPOSE: To determine the long-term risk of retinal detachment following pediatric cataract surgery and to identify risk factors for retinal detachment. METHODS: We included all children (aged 0 to 17 years) who during the time period of 1977 to 2005 underwent pediatric cataract surgery in Denmark...... was based on medical chart review. RESULTS: Among 1043 eyes of 656 children undergoing surgery for pediatric cataract, 25 eyes (23 children) developed retinal detachment at a median time of 9.1 years after surgery. The overall 20-year risk of retinal detachment was 7% (95% confidence interval [CI]: 3...... (16% [95% CI: 6%-24%]). CONCLUSIONS: The estimated overall risk of retinal detachment 20 years after pediatric cataract surgery was 7%, but only 3% for isolated cataract. Particularly high risks of retinal detachment after cataract surgery were associated with mental retardation and having other...

Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

Science.gov (United States)

Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

2011-01-18

Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pigpig). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Multi-diameter pigging: factors affecting the design and selection of pigging tools for multi-diameter pipelines

Energy Technology Data Exchange (ETDEWEB)

Dawson, Karl [Pipeline Engineering and Supply Co. Ltd., Richmond, NY (United States)

2009-07-01

This paper will consider the process involved in pigging tool selection for pipelines with two or more significant internal diameters which require pigging tools capable of negotiating the different internal diameters whilst also carrying out the necessary pipeline cleaning operation. The paper will include an analysis of pipeline features that affect pigging tool selection and then go on to look at other variables that determine the pigging tool design; this will include a step by step guide outlining how the tool is designed, the development of prototype pigs and the importance of testing and validation prior to final deployment in operational pigging programmes. (author)

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.

Brain-inspired algorithms for retinal image analysis

NARCIS (Netherlands)

ter Haar Romeny, B.M.; Bekkers, E.J.; Zhang, J.; Abbasi-Sureshjani, S.; Huang, F.; Duits, R.; Dasht Bozorg, Behdad; Berendschot, T.T.J.M.; Smit-Ockeloen, I.; Eppenhof, K.A.J.; Feng, J.; Hannink, J.; Schouten, J.; Tong, M.; Wu, H.; van Triest, J.W.; Zhu, S.; Chen, D.; He, W.; Xu, L.; Han, P.; Kang, Y.

2016-01-01

Retinal image analysis is a challenging problem due to the precise quantification required and the huge numbers of images produced in screening programs. This paper describes a series of innovative brain-inspired algorithms for automated retinal image analysis, recently developed for the RetinaCheck

Pig but not Human Interferon-γ Initiates Human Cell-Mediated Rejection of Pig Tissue in vivo

Science.gov (United States)

Sultan, Parvez; Murray, Allan G.; McNiff, Jennifer M.; Lorber, Marc I.; Askenase, Philip W.; Bothwell, Alfred L. M.; Pober, Jordan S.

1997-08-01

Split-thickness pig skin was transplanted on severe combined immunodeficient mice so that pig dermal microvessels spontaneously inosculated with mouse microvessels and functioned to perfuse the grafts. Pig endothelial cells in the healed grafts constitutively expressed class I and class II major histocompatibility complex molecules. Major histocompatibility complex molecule expression could be further increased by intradermal injection of pig interferon-γ (IFN-γ ) but not human IFN-γ or tumor necrosis factor. Grafts injected with pig IFN-γ also developed a sparse infiltrate of mouse neutrophils and eosinophils without evidence of injury. Introduction of human peripheral blood mononuclear cells into the animals by intraperitoneal inoculation resulted in sparse perivascular mononuclear cell infiltrates in the grafts confined to the pig dermis. Injection of pig skin grafts on mice that received human peripheral blood mononuclear cells with pig IFN-γ (but not human IFN-γ or heat-inactivated pig IFN-γ ) induced human CD4+ and CD8+ T cells and macrophages to more extensively infiltrate the pig skin grafts and injure pig dermal microvessels. These findings suggest that human T cell-mediated rejection of xenotransplanted pig organs may be prevented if cellular sources of pig interferon (e.g., passenger lymphocytes) are eliminated from the graft.

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.

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.

Isolation of progenitor cells from GFP-transgenic pigs and transplantation to the retina of allorecipients

DEFF Research Database (Denmark)

Klassen, Henry; Warfvinge, Karin; Schwartz, Philip H

2008-01-01

to survival as allografts and integrate into the host retinal architecture, we isolated donor cells from fetal green fluorescent protein (GFP)-transgenic pigs. Cultures were propagated from the brain, retina, and corneo-scleral limbus. GFP expression rapidly increased with time in culture, although lower...... in conjunction with photoreceptor markers and glial fibrillary acid protein (GFAP), thus suggesting downregulation of GFP during differentiation. Following transplantation, GFP expression allowed histological visualization of integrated cells and extension of fine processes to adjacent plexiform layers. GFP...

Simultaneous Mutation Detection in 90 Retinal Disease Genes in Multiple Patients Using a Custom-designed 300-kb Retinal Resequencing Chip

NARCIS (Netherlands)

Booij, Judith C.; Bakker, Arne 1; Kulumbetova, Jamilia; Moutaoukil, Youssef; Smeets, Bert; Verheij, Joke; Kroes, Hester Y.; Klaver, Caroline C. W.; van Schooneveld, Mary; Bergen, Arthur A. B.; Florijn, Ralph J.

Purpose: To develop a high-throughput, cost-effective diagnostic strategy for the identification of known and new mutations in 90 retinal disease genes. Design: Evidence-based study. Participants: Sixty patients with a variety of retinal disorders, including Leber's congenital amaurosis, ocular

Circadian perinatal photoperiod has enduring effects on retinal dopamine and visual function.

Science.gov (United States)

Jackson, Chad R; Capozzi, Megan; Dai, Heng; McMahon, Douglas G

2014-03-26

Visual system development depends on neural activity, driven by intrinsic and light-sensitive mechanisms. Here, we examined the effects on retinal function due to exposure to summer- and winter-like circadian light cycles during development and adulthood. Retinal light responses, visual behaviors, dopamine content, retinal morphology, and gene expression were assessed in mice reared in seasonal photoperiods consisting of light/dark cycles of 8:16, 16:8, and 12:12 h, respectively. Mice exposed to short, winter-like, light cycles showed enduring deficits in photopic retinal light responses and visual contrast sensitivity, but only transient changes were observed for scotopic measures. Dopamine levels were significantly lower in short photoperiod mice, and dopaminergic agonist treatment rescued the photopic light response deficits. Tyrosine hydroxylase and Early Growth Response factor-1 mRNA expression were reduced in short photoperiod retinas. Therefore, seasonal light cycles experienced during retinal development and maturation have lasting influence on retinal and visual function, likely through developmental programming of retinal dopamine.

Manipulating early pig embryos.

Science.gov (United States)

Niemann, H; Reichelt, B

1993-01-01

On the basis of established surgical procedures for embryo recovery and transfer, the early pig embryo can be subjected to various manipulations aimed at a long-term preservation of genetic material, the generation of identical multiplets, the early determination of sex or the alteration of the genetic make-up. Most of these procedures are still at an experimental stage and despite recent considerable progress are far from practical application. Normal piglets have been obtained after cryopreservation of pig blastocysts hatched in vitro, whereas all attempts to freeze embryos with intact zona pellucida have been unsuccessful. Pig embryos at the morula and blastocyst stage can be bisected microsurgically and the resulting demi-embryos possess a high developmental potential in vitro, whereas their development in vivo is impaired. Pregnancy rates are similar (80%) but litter size is reduced compared with intact embryos and twinning rate is approximately 2%. Pig blastomeres isolated from embryos up to the 16-cell stage can be grown in culture and result in normal blastocysts. Normal piglets have been born upon transfer of blastocysts derived from isolated eight-cell blastomeres, clearly underlining the totipotency of this developmental stage. Upon nuclear transfer the developmental capacity of reconstituted pig embryos is low and culture. Sex determination can be achieved either by separation of X and Y chromosome bearing spermatozoa by flow cytometry or by analysing the expression of the HY antigen in pig embryos from the eight-cell to morula stage. Microinjection of foreign DNA has been successfully used to alter growth and development of transgenic pigs, and to produce foreign proteins in the mammary gland or in the bloodstream, indicating that pigs can be used as donors for valuable human pharmaceutical proteins. Another promising area of gene transfer is the increase of disease resistance in transgenic lines of pigs. Approximately 30% of pig spermatozoa bind

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)

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.

Recent developments in cattle, pig, sheep and horse breeding - a review

Directory of Open Access Journals (Sweden)

Alena Svitáková

2014-01-01

Full Text Available The aim of this review was to summarize new genetic approaches and techniques in the breeding of cattle, pigs, sheep and horses. Often production and reproductive traits are treated separately in genetic evaluations, but advantages may accrue to their joint evaluation. A good example is the system in pig breeding. Simplified breeding objectives are generally no longer appropriate and consequently becoming increasingly complex. The goal of selection for improved animal performance is to increase the profit of the production system; therefore, economic selection indices are now used in most livestock breeding programmes. Recent developments in dairy cattle breeding have focused on the incorporation of molecular information into genetic evaluations and on increasing the importance of longevity and health in breeding objectives to maximize the change in profit. For a genetic evaluation of meat yield (beef, pig, sheep, several types of information can be used, including data from performance test stations, records from progeny tests and measurements taken at slaughter. The standard genetic evaluation method of evaluation of growth or milk production has been the multi-trait animal model, but a test-day model with random regression is becoming the new standard, in sheep as well. Reviews of molecular genetics and pedigree analyses for performance traits in horses are described. Genome – wide selection is becoming a world standard for dairy cattle, and for other farm animals it is under development.

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.

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.

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.

Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion

Directory of Open Access Journals (Sweden)

Mason lll JO

2015-06-01

Full Text Available John O Mason III,1,2 Shyam A Patel,1 Richard M Feist,1,2 Michael A Albert Jr,1,2 Carrie Huisingh,1 Gerald McGwin Jr,1,3 Martin L Thomley1,2 1Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL, USA; 2Retina Consultants of Alabama, Callahan Eye Foundation Hospital, Birmingham, AL, USA; 3Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: To investigate the ocular neovascularization (ONV rate in eyes with a branch retinal artery occlusion (BRAO or a central retinal artery occlusion (CRAO, and to study factors that may influence the ONV rate secondary to CRAO.Methods: This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development.Results: Twelve (14.5% of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7% had iris neovascularization, ten of 12 eyes (83.3% had neovascular glaucoma, and two of 12 eyes (16.7% had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0% of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8 (P=0.02.Conclusion: ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV. Keywords: neovascularization, neovascular glaucoma, retinal artery occlusion, central

Towards a Completely Implantable, Light-Sensitive Intraocular Retinal Prosthesis

National Research Council Canada - National Science Library

Humayun, M

2001-01-01

An electronic retinal prosthesis is under development to treat retinitis pigmentosa and age-related macular degeneration, two presently incurable diseases of the outer retina that afflict millions world-wide...

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 ...

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 ...

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.

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.

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.

Relationship between blood-retinal barrier development and formation of selenite nuclear cataract in rat

Directory of Open Access Journals (Sweden)

Ping Lu

2017-12-01

Full Text Available AIM: To investigate the relationship between development of blood-retinal barrier and formation of selenite nuclear cataract in rat. METHODS: Activity of GPx, MDA level in lens and selenium content in the eyeballs of different ages rats were determined. Besides, lanthanum hydroxide \\〖La(OH3\\〗 tracer method was used to detect development status of blood-retina barrier at different ages. RESULTS: The result showed that the enzyme activity of GPx was highest in young rats before open eyes, but then decreased gradually with age. Distribution of La(OH3 in retinal pigment epithelial layer of 20-day-old rats was significantly less than 11-day-old rats. Injecting sodium selenite to 9-day-old rats, lanthanum hydroxide increased obviously and extended to the inner layers of the retina after 48h, and the retinal pigment epithelial layer was damaged seriously; while injecting sodium selenite to 18-day-old rats with the same dose, number of lanthanum hydroxide decreased significantly and did not extend to the inner layer after 48h.Before opening eyes, the content of MDA in the lens of rats was the highest, and decreased significantly after opening eyes. The Se group was 5 times as that of the control group. Besides, in these groups of rats, selenium content in the eyeballs and MDA level in the lens were in agreement with the change of La(OH3 distribution. CONCLUSION: These results indicated that antioxidant capacity in the eyelid unopened rats is not the main reason for selenite induced cataract formation. The real reason is that blood-retina barrier development is not mature in the eyelid unopened rats.

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.

Coats-like retinitis pigmentosa: Reports of three cases.

Science.gov (United States)

Kan, Emrah; Yilmaz, Turgut; Aydemir, Orhan; Güler, Mete; Kurt, Jülide

2007-06-01

Describing the ophthalmic findings of an exudative vasculopathy called as Coats-like retinitis pigmentosa on three patients. The etiology of the Coats-like retinitis pigmentosa is obscure. The principal theories have been discussed in this article. Three observational case series have been discussed. Complete ophthalmic examinations and color fundus photos, visual field, and fluorescein angiography have been performed. We have identified 3 patients who have some typical clinical features of Coats-like retinitis pigmentosa; peripheral serous retinal detachment, telangiectasia, prominent lipid deposition, pigmentary changes in peripheral retina, and loss of vision. None of the three patients had positive family history. All of the patients have had symptoms of nyctalopia, decreased central vision, and two of them have had constriction of visual field. All of the patients have had cataracts and two of them underwent cataract surgery. Fundus examination and fluorescein angiography of patients revealed typical retinitis pigmentosa with Coats-type changes in bilateral inferiotemporal quadrants. A better understanding of clinical features and genetic etiology of Coats-type retinitis pigmentosa will aid diagnosis and development of new therapies. If sufficient conditions arise, genetic factors that influence the expression of CRB1 mutations in Coats-like retinitis pigmentosa should be detected.

Retinal, visual, and refractive development in retinopathy of prematurity

Science.gov (United States)

Moskowitz, Anne; Hansen, Ronald M; Fulton, Anne B

2016-01-01

The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria. On the other hand, deficits in post-receptor sensitivity are present in infancy regardless of the severity of the ROP but are not present in older children if the ROP was so mild that it never required treatment and resolved without a clinical trace. Accompanying the persistent deficits in photoreceptor sensitivity, there is increased receptive field size and thickening of the post-receptor retinal laminae in the peripheral retina of ROP subjects. In the late maturing central retina, which mediates visual acuity, attenuation of multifocal electroretinogram activity in the post-receptor retina led us to the discovery of a shallow foveal pit and significant thickening of the post-receptor retinal laminae in the macular region; this is most likely due to failure of the normal centrifugal movement of the post-receptor cells during foveal development. As for refractive development, myopia, at times high, is more common in ROP subjects than in control subjects, in accord with refractive findings in other populations of former preterms. This information about the neurosensory retina enhances understanding of vision in patients with a history of ROP, and taken as a whole, raises the possibility that the neurosensory retina is a target for therapeutic intervention. PMID:28539805

Spectrally optimal illuminations for diabetic retinopathy detection in retinal imaging

Science.gov (United States)

Bartczak, Piotr; Fält, Pauli; Penttinen, Niko; Ylitepsa, Pasi; Laaksonen, Lauri; Lensu, Lasse; Hauta-Kasari, Markku; Uusitalo, Hannu

2017-04-01

Retinal photography is a standard method for recording retinal diseases for subsequent analysis and diagnosis. However, the currently used white light or red-free retinal imaging does not necessarily provide the best possible visibility of different types of retinal lesions, important when developing diagnostic tools for handheld devices, such as smartphones. Using specifically designed illumination, the visibility and contrast of retinal lesions could be improved. In this study, spectrally optimal illuminations for diabetic retinopathy lesion visualization are implemented using a spectrally tunable light source based on digital micromirror device. The applicability of this method was tested in vivo by taking retinal monochrome images from the eyes of five diabetic volunteers and two non-diabetic control subjects. For comparison to existing methods, we evaluated the contrast of retinal images taken with our method and red-free illumination. The preliminary results show that the use of optimal illuminations improved the contrast of diabetic lesions in retinal images by 30-70%, compared to the traditional red-free illumination imaging.

Retinal Endovascular Surgery with Tissue Plasminogen Activator Injection for Central Retinal Artery Occlusion

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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.

Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen

Directory of Open Access Journals (Sweden)

Hadanny A

2016-12-01

Full Text Available Amir Hadanny,1,2 Amit Maliar,1 Gregory Fishlev,1 Yair Bechor,1 Jacob Bergan,1 Mony Friedman,1 Isaac Avni,2,3 Shai Efrati1,2,4,5 1Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Zerifin, Israel; 2Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 3Opthalmology Department, Assaf Harofeh Medical Center, Zeirifin, Israel; 4Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel; 5Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel Purpose: Ischemic retinal damage can be reversed by hyperbaric oxygen therapy (HBOT as long as irreversible infarction damage has not developed. However, the time window till irreversible damage develops is still unknown. The study aim was to evaluate the effect of HBOT and determine possible markers for irreversible retinal damage.Materials and methods: Retrospective analysis of 225 patients treated with HBOT for central retinal artery occlusion (CRAO in 1999–2015. One hundred and twenty-eight patients fulfilled inclusion/exclusion criteria: age >18 years, symptoms <20 hours, and best-corrected visual acuity (BCVA <0.5 logMAR.Results: Time delay from symptoms to treatment was 7.8±3.8 hours. The BCVA was significantly improved after HBOT, from 2.14±0.50 to 1.61±0.78 (P<0.0001. The proportion of patients with clinically meaningful visual improvement was significantly higher in patients without cherry-red spot (CRS compared to patients with CRS at presentation (86.0% vs 57.6%, P<0.0001. The percentage of patients with final BCVA better than 1.0 was also significantly higher in patients without CRS vs patients with CRS at presentation (61.0% vs 7.1%, P<0.0001. There was no correlation between CRS and the time from symptoms. HBOT was found to be safe, and only 5.5% of patients had minor, reversible, adverse events.Conclusion: HBOT is an effective treatment for non-arteritic CRAO as long as CRS has not formed. The fundus findings, rather

[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.

Retinal image restoration by means of blind deconvolution

Science.gov (United States)

Marrugo, Andrés G.; Šorel, Michal; Šroubek, Filip; Millán, María S.

2011-11-01

Retinal imaging plays a key role in the diagnosis and management of ophthalmologic disorders, such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Because of the acquisition process, retinal images often suffer from blurring and uneven illumination. This problem may seriously affect disease diagnosis and progression assessment. Here we present a method for color retinal image restoration by means of multichannel blind deconvolution. The method is applied to a pair of retinal images acquired within a lapse of time, ranging from several minutes to months. It consists of a series of preprocessing steps to adjust the images so they comply with the considered degradation model, followed by the estimation of the point-spread function and, ultimately, image deconvolution. The preprocessing is mainly composed of image registration, uneven illumination compensation, and segmentation of areas with structural changes. In addition, we have developed a procedure for the detection and visualization of structural changes. This enables the identification of subtle developments in the retina not caused by variation in illumination or blur. The method was tested on synthetic and real images. Encouraging experimental results show that the method is capable of significant restoration of degraded retinal images.

Hypoxia inducible factor-2α regulates the development of retinal astrocytic network by maintaining adequate supply of astrocyte progenitors.

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Li-Juan Duan

Full Text Available Here we investigate the role of hypoxia inducible factor (HIF-2α in coordinating the development of retinal astrocytic and vascular networks. Three Cre mouse lines were used to disrupt floxed Hif-2α, including Rosa26(CreERT2, Tie2(Cre, and GFAP(Cre. Global Hif-2α disruption by Rosa26(CreERT2 led to reduced astrocytic and vascular development in neonatal retinas, whereas endothelial disruption by Tie2(Cre had no apparent effects. Hif-2α deletion in astrocyte progenitors by GFAP(Cre significantly interfered with the development of astrocytic networks, which failed to reach the retinal periphery and were incapable of supporting vascular development. Perplexingly, the abundance of strongly GFAP(+ mature astrocytes transiently increased at P0 before they began to lag behind the normal controls by P3. Pax2(+ and PDGFRα(+ astrocytic progenitors and immature astrocytes were dramatically diminished at all stages examined. Despite decreased number of astrocyte progenitors, their proliferation index or apoptosis was not altered. The above data can be reconciled by proposing that HIF-2α is required for maintaining the supply of astrocyte progenitors by slowing down their differentiation into non-proliferative mature astrocytes. HIF-2α deficiency in astrocyte progenitors may accelerate their differentiation into astrocytes, a change which greatly interferes with the replenishment of astrocyte progenitors due to insufficient time for proliferation. Rapidly declining progenitor supply may lead to premature cessation of astrocyte development. Given that HIF-2α protein undergoes oxygen dependent degradation, an interesting possibility is that retinal blood vessels may regulate astrocyte differentiation through their oxygen delivery function. While our findings support the consensus that retinal astrocytic template guides vascular development, they also raise the possibility that astrocytic and vascular networks may mutually regulate each other

Scleral buckling for retinal detachment in patients with retinoblastoma

International Nuclear Information System (INIS)

Buzney, S.M.; Pruett, R.C.; Regan, C.D.; Walton, D.S.; Smith, T.R.

1984-01-01

Three children (two girls and one boy) with bilateral retinoblastoma each developed a presumed rhegmatogenous retinal detachment in one eye. All three eyes had previously received radiation and cryotherapy. In each case the retinal detachment responded promptly to conventional surgical methods via scleral buckling in the area of treated retinoblastoma and presumed retinal break. All three eyes have retained useful vision for follow-up periods of 3.5 to 12 years

Scleral buckling for retinal detachment in patients with retinoblastoma

Energy Technology Data Exchange (ETDEWEB)

Buzney, S.M.; Pruett, R.C.; Regan, C.D.; Walton, D.S.; Smith, T.R.

1984-10-15

Three children (two girls and one boy) with bilateral retinoblastoma each developed a presumed rhegmatogenous retinal detachment in one eye. All three eyes had previously received radiation and cryotherapy. In each case the retinal detachment responded promptly to conventional surgical methods via scleral buckling in the area of treated retinoblastoma and presumed retinal break. All three eyes have retained useful vision for follow-up periods of 3.5 to 12 years.

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

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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

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.

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.

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment Update

Science.gov (United States)

Lee, Christine; Tu, Hong Anh; Wells, David; Holubowich, Corinne

2017-01-01

Background Retinitis pigmentosa is a group of inherited disorders characterized by the degeneration of the photoreceptors in the retina, resulting in progressive vision loss. The Argus II system is designed to restore partial functional vision in patients with profound vision loss from advanced retinitis pigmentosa. At present, it is the only treatment option approved by Health Canada for this patient population. In June 2016, Health Quality Ontario published a health technology assessment of the Argus II retinal prosthesis system for patients with advanced retinitis pigmentosa. Based on that assessment, the Ontario Health Technology Advisory Committee recommended against publicly funding the Argus II system for this population. It also recommended that Health Quality Ontario re-evaluate the evidence in 1 year. The objective of this report was to examine new evidence published since the 2016 health technology assessment. Methods We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences related to the Argus II system. We performed a systematic literature search for studies published since the 2016 Argus II health technology assessment. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care, and we calculated incremental cost-effectiveness ratios over a 20-year time horizon. We also conducted a five-year budget impact analysis. Finally, we interviewed people with retinitis pigmentosa about their lived experience with vision loss, and with the Argus II system. Results Four publications from one multicentre international study were included in the clinical review. Patients showed significant improvements in visual function and functional outcomes with the Argus II system, and these outcomes were sustained up to a 5-year follow-up (moderate quality of evidence). The safety profile was generally acceptable. In

Optic nerve head and intraocular pressure in the guinea pig eye.

Science.gov (United States)

Ostrin, Lisa A; Wildsoet, Christine F

2016-05-01

The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I-V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were

Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development

DEFF Research Database (Denmark)

Petersen, Y. M.; Hartmann, B.; Holst, Jens Juul

2003-01-01

increased before birth, peaked in suckling 1-d-old pigs (87 +/- 14 pmol/L, P anorexia (34 +/- 5 pmol/L, P ... in these pigs. We conclude that the introduction of enteral feeding transiently increases plasma GLP-2 concentrations and decreases small intestinal GLP-2R mRNA levels during pig development. GLP-2 may play a role in the growth of the small intestine around birth and weaning via a response to enteral nutrition....

Programming Pig

CERN Document Server

Gates, Alan

2011-01-01

This guide is an ideal learning tool and reference for Apache Pig, the open source engine for executing parallel data flows on Hadoop. With Pig, you can batch-process data without having to create a full-fledged application-making it easy for you to experiment with new datasets. Programming Pig introduces new users to Pig, and provides experienced users with comprehensive coverage on key features such as the Pig Latin scripting language, the Grunt shell, and User Defined Functions (UDFs) for extending Pig. If you need to analyze terabytes of data, this book shows you how to do it efficiently

Retinal stem cells and potential cell transplantation treatments

Directory of Open Access Journals (Sweden)

Tai-Chi Lin

2014-11-01

Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

Adenocarcinoma of the gallbladder in guinea pigs

International Nuclear Information System (INIS)

Hoch-Ligeti, C.; Congdon, C.C.; Deringer, M.K.; Stewart, H.L.

1979-01-01

Adenocarcinoma of the gallbladder developed in 17 of 68 untreated and in 26 of 83 irradiated guinea pigs of inbred strains 2 and 13. The carcinomas spread widely by direct extension and through lymphatic and blood vessels to lymph nodes, mesenteries, omenta, abdominal wall, liver, lungs, bones, and spleen. Whole-body exposure to gamma or x radiation increased both the number of tumors and metastases in male inbred guinea pigs but not in females. Significantly fewer (9 of 98) noninbred than inbred guinea pigs developed gallbladder carcinomas after irradiation. In 9 untreated noninbred guinea pigs gallbladder carcinomas were not found. Inasmuch as the effect of irradiation was not dose-dependent, an indirect systemic effect of irradiation was postulated. This is the first report on the occurrence of spontaneous gallbladder adenocarcinomas in guinea pigs

Instrumented PIG's field performance; Desenvolvimento de PIG MFL de alta resolucao

Energy Technology Data Exchange (ETDEWEB)

Camerini, Claudio Soligo; Oliveira, Carlos H.F. de; Nazario, Fabiana; Sant' Anna, Antonio Claudio [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES); Silva, Jos Augusto; Janvrot, Ivan Vicente [PipeWay Engenharia, Rio de Janeiro, RJ (Brazil); Weid, Jean Pierre Van Der; Lima, Vinicius; Freitas, Miguel; Domingos, Luis Carlos [Pontificia Univ. Catolica do Rio de Janeiro, RJ (Brazil). Centro de Estudos em Telecomunicacoes; Silva, Guttemberg C. da [Chemtech Ltda., Rio de Janeiro, RJ (Brazil)

2003-07-01

About ten years ago PETROBRAS and PUC-Rio started a cooperation agreement aiming the development of intelligent PIG technology for pipeline inspection. The PETROBRAS R and D center (CENPES) and PUC' Center for Telecommunications Studies (CETUC) were the research units involved in this technological partnership. Many different results were generated from this 10-year work, including a spin-off company for the commercialization of the results. Within this work, the development of a high resolution magnetic PIG - MFL PIG - which is the main pipeline inspection tool and central theme of the technological partnership. Technical features of the development are described, such as the evolution of the detected signal quality and resolution, test beds, etc. The cooperation between PETROBRAS and PUC-Rio, the financial support of the government agency FINEP, as well as the technology license, which allowed the commercial use of the technology, are also described. (author)

Repetitive magnetic stimulation improves retinal function in a rat model of retinal dystrophy

Science.gov (United States)

Rotenstreich, Ygal; Tzameret, Adi; Levi, Nir; Kalish, Sapir; Sher, Ifat; Zangen, Avraham; Belkin, Michael

2014-02-01

Vision incapacitation and blindness associated with retinal dystrophies affect millions of people worldwide. Retinal degeneration is characterized by photoreceptor cell death and concomitant remodeling of remaining retinal cells. Repetitive Magnetic Stimulation (RMS) is a non-invasive technique that creates alternating magnetic fields by brief electric currents transmitted through an insulated coil. These magnetic field generate action potentials in neurons, and modulate the expression of neurotransmitter receptors, growth factors and transcription factors which mediate plasticity. This technology has been proven effective and safe in various psychiatric disorders. Here we determined the effect of RMS on retinal function in Royal College of Surgeons (RCS) rats, a model for retinal dystrophy. Four week-old RCS and control Spargue Dawley (SD) rats received sham or RMS treatment over the right eye (12 sessions on 4 weeks). RMS treatment at intensity of at 40% of the maximal output of a Rapid2 stimulator significantly increased the electroretinogram (ERG) b-wave responses by up to 6- or 10-fold in the left and right eye respectively, 3-5 weeks following end of treatment. RMS treatment at intensity of 25% of the maximal output did not significant effect b-wave responses following end of treatment with no adverse effect on ERG response or retinal structure of SD rats. Our findings suggest that RMS treatment induces delayed improvement of retinal functions and may induce plasticity in the retinal tissue. Furthermore, this non-invasive treatment may possibly be used in the future as a primary or adjuvant treatment for retinal dystrophy.

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.

The Edge Detectors Suitable for Retinal OCT Image Segmentation

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Su Luo

2017-01-01

Full Text Available Retinal layer thickness measurement offers important information for reliable diagnosis of retinal diseases and for the evaluation of disease development and medical treatment responses. This task critically depends on the accurate edge detection of the retinal layers in OCT images. Here, we intended to search for the most suitable edge detectors for the retinal OCT image segmentation task. The three most promising edge detection algorithms were identified in the related literature: Canny edge detector, the two-pass method, and the EdgeFlow technique. The quantitative evaluation results show that the two-pass method outperforms consistently the Canny detector and the EdgeFlow technique in delineating the retinal layer boundaries in the OCT images. In addition, the mean localization deviation metrics show that the two-pass method caused the smallest edge shifting problem. These findings suggest that the two-pass method is the best among the three algorithms for detecting retinal layer boundaries. The overall better performance of Canny and two-pass methods over EdgeFlow technique implies that the OCT images contain more intensity gradient information than texture changes along the retinal layer boundaries. The results will guide our future efforts in the quantitative analysis of retinal OCT images for the effective use of OCT technologies in the field of ophthalmology.

Hemi-central retinal artery occlusion in young adults

Directory of Open Access Journals (Sweden)

Rishi Pukhraj

2010-01-01

Full Text Available Amongst the clinical presentations of retinal artery occlusion, hemi-central retinal artery occlusion (Hemi-CRAO is rarely described. This case series of four adults aged between 22 and 36 years attempts to describe the clinical profile, etiology and management of Hemi-CRAO. Case 1 had an artificial mitral valve implant. Polycythemia and malignant hypertension were noted in Case 2. The third patient had Leiden mutation while the fourth patient had Eisenmenger′s syndrome. Clinical examination and fundus fluorescein angiography revealed a bifurcated central retinal artery at emergence from the optic nerve head, in all cases. Color Doppler examination of the central retinal artery confirmed branching of the artery behind the lamina cribrosa. It is hypothesized that bifurcation of central retinal artery behind the lamina cribrosa may predispose these hemi-trunks to develop an acute occlusion if associated with underlying risk factors. The prognosis depends upon arterial recanalisation and etiology of the thromboembolic event.

All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice

Science.gov (United States)

Strazzeri, Jennifer M.; Williams, David R.; Merigan, William H.

2018-01-01

Here we demonstrate the application of a method that could accelerate the development of novel therapies by allowing direct and repeatable visualization of cellular function in the living eye, to study loss of vision in animal models of retinal disease, as well as evaluate the time course of retinal function following therapeutic intervention. We use high-resolution adaptive optics scanning light ophthalmoscopy to image fluorescence from the calcium sensor GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored visual responses in ganglion cell layer neurons expressing the red-shifted channelrhodopsin ChrimsonR over a six-week period following significant loss of visual responses. Combining a fluorescent calcium sensor, a channelrhodopsin, and adaptive optics enables all-optical stimulation and recording of retinal neurons in the living eye. Because the retina is an accessible portal to the central nervous system, our method also provides a novel non-invasive method of dissecting neuronal processing in the brain. PMID:29596518

ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

OpenAIRE

Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

2011-01-01

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and i...

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.

Development of a guinea pig cutaneous radiation injury model using low penetrating X-rays.

Science.gov (United States)

Rodgers, Kathleen E; Tan, Alick; Kim, Lila; Espinoza, Theresa; Meeks, Christopher; Johnston, William; Maulhardt, Holly; Donald, Melissa; Hill, Colin; diZerega, Gere S

2016-08-01

A guinea pig skin model was developed to determine the dose-dependent response to soft X-ray radiation into the dermis. X-ray exposure (50 kVp) was defined to a 4.0 × 4.0 cm area on the lateral surface of a guinea pig using lead shielding. Guinea pigs were exposed to a single fraction of X-ray irradiation ranging from 25-79 Gy via an XRAD320ix Biological Irradiator with the collimator removed. Gross skin changes were measured using clinical assessments defined by the Kumar scale. Skin contracture was assessed, as well as histological evaluations. Loss of dermal integrity was shown after a single dose of soft X-ray radiation at or above 32 Gy with the central 2.0 × 2.0 cm of the exposed site being the most affected. Hallmarks of the skin injury included moist desquamation, ulceration and wound contracture, as well as alterations in epithelium, dermis, muscle and adipose. Changes in the skin were time- and radiation dose-dependent. Full-thickness injury occurred without animal mortality or gross changes in the underlying organs. The guinea pig is an appropriate small animal model for the short-term screening of countermeasures for cutaneous radiation injury (CRI).

Retinal oxygen saturation in relation to retinal thickness in diabetic macular edema

DEFF Research Database (Denmark)

Blindbæk, Søren Leer; Peto, Tunde; Grauslund, Jakob

to retinal thickness in patients with diabetic macular edema (DME). Methods: We included 18 patients with DME that all had central retinal thickness (CRT) >300 µm and were free of active proliferative diabetic retinopathy. Optical coherence tomography (Topcon 3D OCT-2000 spectral domain OCT) was used...... for paracentral edema, the oxygen saturation in the upper and lower temporal arcade branches were compared to the corresponding upper and lower subfield thickness. Spearman’s rank was used to calculate correlation coefficients between CRT and retinal oximetry. Results: Median age and duration of diabetes was 59....... 92.3%, p=0.52). We found no correlation between CRT and retinal oxygen saturation, even when accounting for paracentral edema (p>0.05). Furthermore, there was no difference in retinal oxygen saturation between the macular hemisphere that was more or less affected by DME (p>0.05). Conclusion: Patients...

ROLE OF TYROSINE-SULFATED PROTEINS IN RETINAL STRUCTURE AND FUNCTION

Science.gov (United States)

Kanan, Y.; Al-Ubaidi, M.R.

2014-01-01

The extracellular matrix (ECM) plays a significant role in cellular and retinal health. The study of retinal tyrosine-sulfated proteins is an important first step toward understanding the role of ECM in retinal health and diseases. These secreted proteins are members of the retinal ECM. Tyrosine sulfation was shown to be necessary for the development of proper retinal structure and function. The importance of tyrosine sulfation is further demonstrated by the evolutionary presence of tyrosylprotein sulfotransferases, enzymes that catalyze proteins’ tyrosine sulfation, and the compensatory abilities of these enzymes. Research has identified four tyrosine-sulfated retinal proteins: fibulin 2, vitronectin, complement factor H (CFH), and opticin. Vitronectin and CFH regulate the activation of the complement system and are involved in the etiology of some cases of age-related macular degeneration. Analysis of the role of tyrosine sulfation in fibulin function showed that sulfation influences the protein's ability to regulate growth and migration. Although opticin was recently shown to exhibit anti-angiogenic properties, it is not yet determined what role sulfation plays in that function. Future studies focusing on identifying all of the tyrosine-sulfated retinal proteins would be instrumental in determining the impact of sulfation on retinal protein function in retinal homeostasis and diseases. PMID:25819460

Retinal complications after aqueous shunt surgical procedures for glaucoma.

Science.gov (United States)

Law, S K; Kalenak, J W; Connor, T B; Pulido, J S; Han, D P; Mieler, W F

1996-12-01

To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

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Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

2016-12-01

To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs.

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Bierle, Craig J; Fernández-Alarcón, Claudia; Hernandez-Alvarado, Nelmary; Zabeli, Jason C; Janus, Bradley C; Putri, Dira S; Schleiss, Mark R

2017-01-01

Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development.

Hypoxia-ischemia and retinal ganglion cell damage

Directory of Open Access Journals (Sweden)

Charanjit Kaur

2008-08-01

Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

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...

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.

Development of Bacillus subtilis mutants to produce tryptophan in pigs

DEFF Research Database (Denmark)

Bjerre, Karin; Cantor, Mette D.; Nørgaard, Jan Værum

2017-01-01

Objectives To generate tryptophan-overproducing Bacillus subtilis strains for in situ use in pigs, to reduce the feed cost for farmers and nitrogen pollution. Results A novel concept has been investigated—to generate B. subtilis strains able to produce tryptophan (Trp) in situ in pigs. Mutagenesis......-excreting B. subtilis strains were obtained with UV-mutagenesis and analogue selection and can be used in animal feed applications....

Development of bio-gas using crop wastes and pig dung ...

African Journals Online (AJOL)

Effect of crop wastes on the production of pig dung bio-gas was investigated. Beans husks, peels of cassava, plantain and yam were processed with fresh dung of pig. Bacterial and fungal counts in the digesting materials ranged from 1.5 x 1011cfu/ml to 3.5 x 1011cfu/ml and 0.8 x 1011sfu/ml to 1.4 x1011sfu/ml respectively.

Retinal single-layer analysis with optical coherence tomography shows inner retinal layer thinning in Huntington's disease as a potential biomarker.

Science.gov (United States)

Gulmez Sevim, Duygu; Unlu, Metin; Gultekin, Murat; Karaca, Cagatay

2018-02-12

There have been ongoing clinical trials of therapeutic agents in Huntington's disease (HD) which requires development of reliable biomarkers of disease progression. There have been studies in the literature with conflicting results on the involvement of retina in HD, and up to date there is not a study evaluating the single retinal layers in HD. We aimed to evaluate the specific retinal changes in HD and their usability as potential disease progression markers. This cross-sectional study used spectral-domain optical coherence tomography with automatic segmentation to measure peripapillary retinal nerve fiber layer (pRNFL) thickness and the thickness and volume of retinal layers in foveal scans of 15 patients with HD and 15 age- and sex-matched controls. Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scales motor scores were acquired for the patients. Temporal pRNFL, macular RNFL (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer and outer plexiform layer thicknesses and IPL, retinal pigment epithelium and outer macular volume were found lower in HD compared to controls, while outer nuclear layer and outer retinal layer thickness were increased (p layer thicknesses, most significantly with mRNFL and GCL and disease progression markers. The outcomes of this study points out that retinal layers, most significantly mRNFL and GCL, are strongly correlated with the disease progression in HD and could serve as useful biomarkers for disease progression.

Study of the orientation of retinal in bovine rhodopsin: the use of a photoactivatable retinal analog

International Nuclear Information System (INIS)

Nakayama, T.

1987-01-01

Rhodopsin is the major transmembrane protein in the photoreceptor cells of vertebrate and invertebrate retina. Bovine rhodopsin consists of a polypeptide chain of 348 amino acids of known sequence in which the chromophore, 11-cis-retinal, is linked to Lys-296 as a Schiff base. To investigate the orientation of retinal in the protein and to study the interactions between retinal and the protein, the authors have developed a crosslinking approach using a 3 H-labeled photoactivatable analog of retinal. Bleached rhodopsin in rod outer segments was reconstituted with the analog to give a pigment with λ/sub max/ at 460nm. Reduction of the Schiff base with borane dimenthylamine, followed by degradation with CNBr and sequencing of the radioactive fragment showed that the analog is attached to Lys-296, as in the native rhodopsin. Further, the reconstitute protein after photolysis was phosphorylated by rhodopsin kinase. Photolysis of the reconstituted pigment at -15 0 C resulted in crosslinking of the analog to the opsin to the extent of 30% as analyzed by SDS electrophoresis. The site(s) of crosslinking in the protein are under investigation

Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan

Science.gov (United States)

Chen, San-Ni; Hwang, Jiunn-Feng; Wu, Wen-Chuan

2016-01-01

This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. PMID:26909812

Genetic characterization and disease mechanism of retinitis pigmentosa; current scenario.

Science.gov (United States)

Ali, Muhammad Umar; Rahman, Muhammad Saif Ur; Cao, Jiang; Yuan, Ping Xi

2017-08-01

Retinitis pigmentosa is a group of genetically transmitted disorders affecting 1 in 3000-8000 individual people worldwide ultimately affecting the quality of life. Retinitis pigmentosa is characterized as a heterogeneous genetic disorder which leads by progressive devolution of the retina leading to a progressive visual loss. It can occur in syndromic (with Usher syndrome and Bardet-Biedl syndrome) as well as non-syndromic nature. The mode of inheritance can be X-linked, autosomal dominant or autosomal recessive manner. To date 58 genes have been reported to associate with retinitis pigmentosa most of them are either expressed in photoreceptors or the retinal pigment epithelium. This review focuses on the disease mechanisms and genetics of retinitis pigmentosa. As retinitis pigmentosa is tremendously heterogeneous disorder expressing a multiplicity of mutations; different variations in the same gene might induce different disorders. In recent years, latest technologies including whole-exome sequencing contributing effectively to uncover the hidden genesis of retinitis pigmentosa by reporting new genetic mutations. In future, these advancements will help in better understanding the genotype-phenotype correlations of disease and likely to develop new therapies.

RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis

International Nuclear Information System (INIS)

Liu, Chang; Li, Chao-peng; Wang, Jia-Jian; Shan, Kun; Liu, Xin; Yan, Biao

2016-01-01

Retinal reactive gliosis is an important pathological feature of diabetic retinopathy. Identifying the underlying mechanisms causing reactive gliosis will be important for developing new therapeutic strategies for treating diabetic retinopathy. Herein, we show that long noncoding RNA-RNCR3 knockdown significantly inhibits retinal reactive gliosis. RNCR3 knockdown leads to a marked reduction in the release of several cytokines. RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration, as shown by less apoptotic retinal cells and ameliorative visual function. RNCR3 knockdown could also decrease Müller glial cell viability and proliferation, and reduce the expression of glial reactivity-related genes including GFAP and vimentin in vitro. Collectively, this study shows that RNCR3 knockdown may be a promising strategy for the prevention of diabetes mellitus-induced retinal neurodegeneration. - Highlights: • RNCR3 knockdown inhibits retinal reactive gliosis. • RNCR3 knockdown causes a significant change in cytokine profile. • RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration. • RNCR3 knockdown affects Müller glial cell function in vitro.

Bilateral retinal vein occlusion and rubeosis irides: lessons to learn.

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Md Noh, Umi Kalthum; Ahem, Amin; Mustapha, Mushawiahti

2013-01-01

Uncontrolled hypertension is well- known to give rise to systemic complications involving multiple central organs. Artherosclerosis leads to damage of the retinal vessels wall, contributing to venous stasis, thrombosis and finally, occlusion. Retinal vein occlusions compromise vision through development of ischaemic maculopathy, macular oedema, and rubeotic glaucoma. Laser photocoagulation remains the definitive treatment for ischaemic vein occlusion with secondary neovascularization. Timely treatment with anti- vascular endothelial growth factor prevents development of rubeotic glaucoma. We hereby report an unusual case of bilateral retinal vein occlusion complicated by rubeosis irides, which was successfully managed to improve vision and prevent rubeotic glaucoma.

Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration.

Science.gov (United States)

Burnight, Erin R; Gupta, Manav; Wiley, Luke A; Anfinson, Kristin R; Tran, Audrey; Triboulet, Robinson; Hoffmann, Jeremy M; Klaahsen, Darcey L; Andorf, Jeaneen L; Jiao, Chunhua; Sohn, Elliott H; Adur, Malavika K; Ross, Jason W; Mullins, Robert F; Daley, George Q; Schlaeger, Thorsten M; Stone, Edwin M; Tucker, Budd A

2017-09-06

Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function. We developed a homology-directed repair strategy targeting a homozygous Alu insertion in exon 9 of male germ cell-associated kinase (MAK) and demonstrated restoration of the retinal transcript and protein in patient cells. We generated a CRISPR-Cas9-mediated non-homologous end joining (NHEJ) approach to excise a major contributor to Leber congenital amaurosis, the IVS26 cryptic-splice mutation in CEP290, and demonstrated correction of the transcript and protein in patient iPSCs. Lastly, we designed allele-specific CRISPR guides that selectively target the mutant Pro23His rhodopsin (RHO) allele, which, following delivery to both patient iPSCs in vitro and pig retina in vivo, created a frameshift and premature stop that would prevent transcription of the disease-causing variant. The strategies developed in this study will prove useful for correcting a wide range of genetic variants in genes that cause inherited retinal degeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

Science.gov (United States)

Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

2014-06-30

The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea in nursery pigs on treatment-efficacy and resistance development

DEFF Research Database (Denmark)

Larsen, I.; Mellerup, Anders; Zachariasen, C.

2015-01-01

A Danish research project, MINIRESIST, investigated the consequences of varying doses and treatment strategies for oxytetracycline treatment of Lawsonia intracellularis diarrhea in nursery pigs. Batches of nursery pigs in five herds were randomly allocated to one of five treatment protocols (batch...... scores, which have low sensitivity for diarrhea. Simulation studies suggested that resistance development was mostly dependent on the duration of the treatment and the total amount of oxytetracycline used per pig. Ongoing field testing has been initiated to confirm this conclusion, since no field...

Developing an item bank to measure the coping strategies of people with hereditary retinal diseases.

Science.gov (United States)

Prem Senthil, Mallika; Khadka, Jyoti; De Roach, John; Lamey, Tina; McLaren, Terri; Campbell, Isabella; Fenwick, Eva K; Lamoureux, Ecosse L; Pesudovs, Konrad

2018-05-05

Our understanding of the coping strategies used by people with visual impairment to manage stress related to visual loss is limited. This study aims to develop a sophisticated coping instrument in the form of an item bank implemented via Computerised adaptive testing (CAT) for hereditary retinal diseases. Items on coping were extracted from qualitative interviews with patients which were supplemented by items from a literature review. A systematic multi-stage process of item refinement was carried out followed by expert panel discussion and cognitive interviews. The final coping item bank had 30 items. Rasch analysis was used to assess the psychometric properties. A CAT simulation was carried out to estimate an average number of items required to gain precise measurement of hereditary retinal disease-related coping. One hundred eighty-nine participants answered the coping item bank (median age = 58 years). The coping scale demonstrated good precision and targeting. The standardised residual loadings for items revealed six items grouped together. Removal of the six items reduced the precision of the main coping scale and worsened the variance explained by the measure. Therefore, the six items were retained within the main scale. Our CAT simulation indicated that, on average, less than 10 items are required to gain a precise measurement of coping. This is the first study to develop a psychometrically robust coping instrument for hereditary retinal diseases. CAT simulation indicated that on an average, only four and nine items were required to gain measurement at moderate and high precision, respectively.

Detection of retinal nerve fiber layer defects in retinal fundus images using Gabor filtering

Science.gov (United States)

Hayashi, Yoshinori; Nakagawa, Toshiaki; Hatanaka, Yuji; Aoyama, Akira; Kakogawa, Masakatsu; Hara, Takeshi; Fujita, Hiroshi; Yamamoto, Tetsuya

2007-03-01

Retinal nerve fiber layer defect (NFLD) is one of the most important findings for the diagnosis of glaucoma reported by ophthalmologists. However, such changes could be overlooked, especially in mass screenings, because ophthalmologists have limited time to search for a number of different changes for the diagnosis of various diseases such as diabetes, hypertension and glaucoma. Therefore, the use of a computer-aided detection (CAD) system can improve the results of diagnosis. In this work, a technique for the detection of NFLDs in retinal fundus images is proposed. In the preprocessing step, blood vessels are "erased" from the original retinal fundus image by using morphological filtering. The preprocessed image is then transformed into a rectangular array. NFLD regions are observed as vertical dark bands in the transformed image. Gabor filtering is then applied to enhance the vertical dark bands. False positives (FPs) are reduced by a rule-based method which uses the information of the location and the width of each candidate region. The detected regions are back-transformed into the original configuration. In this preliminary study, 71% of NFLD regions are detected with average number of FPs of 3.2 per image. In conclusion, we have developed a technique for the detection of NFLDs in retinal fundus images. Promising results have been obtained in this initial study.

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Directory of Open Access Journals (Sweden)

Andreas Ebneter

Full Text Available Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001 compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001. Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

Relationship between retinal lattice degeneration and open angle glaucoma.

Science.gov (United States)

Rahimi, Mansour

2005-01-01

Patients with retinal disorders may develop glaucoma of both a primary and secondary type. Pigment may contribute to trabecular obstruction in some patients with open-angle glaucoma. Lattice degeneration of the retina in its typical form is a sharply demarcated, circumferentially oriented, degenerative process with significant alterations of retinal pigmentation. The association between myopia, open angle glaucoma and pigment dispersion is striking. Therefore, it could be postulated that there is significant prevalence of open angle glaucoma in patients with retinal lattice degeneration, especially in combination with myopia.

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

CERKL knockdown causes retinal degeneration in zebrafish.

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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.

Development and characterization of a guinea pig model for Marburg virus

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Gary Wong

2018-01-01

Full Text Available The Angolan strain of Marburg virus (MARV/Ang can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang-GA. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7–9 days after infection, and the LD50 was calculated to be 1.1×10–1 TCID50 (median tissue culture infective dose. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

Retinal changes in pregnancy-induced hypertension

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Akash Pankaj Shah

2015-01-01

Full Text Available Aims: The aim was to determine the prevalence of retinal changes in pregnancy-induced hypertension (PIH and any association between the retinal changes and age, parity, blood pressure, proteinuria, and severity of the disease. Settings and Design: Hospital-based cross-sectional study. Materials and Methods: All the patients admitted with a diagnosis of PIH were included in this study. Age, gravida, gestation period, blood pressure, and proteinuria were noted from the case records. Fundus examination was done with a direct ophthalmoscope. The findings were noted and were analyzed using SPSS program. Results: A total of 150 patients of PIH were examined. The mean age of patients was 25.1 years. The gestation period ranged from 27 weeks to 42 weeks; 76 (50.67% were the primi gravida. 92 (61.33% patients had gestational hypertension, 49 (32.67% patients had preeclampsia, and 9 (6% had eclampsia. Retinal changes (hypertensive retinopathy were noted in 18 (12% patients - Grade 1 in 12 (8% and Grade 2 in 6 (4%. Hemorrhages or exudates or retinal detachment were not seen in any patient. There was statistically significant positive association of retinal changes and blood pressure (P = 0.037, proteinuria (P = 0.0005, and severity of the PIH (P = 0.004. Conclusions: Retinal changes were seen in 12% of patients with PIH. Occurrence of hypertensive retinopathy in PIH cases has been decreased due to better antenatal care and early detection and treatment of PIH cases. There is a greater chance of developing retinopathy with increase in blood pressure, severity of PIH, and proteinuria in cases of PIH.

Domestication and cereal feeding developed domestic pig-type intestinal microbiota in animals of suidae.

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Ushida, Kazunari; Tsuchida, Sayaka; Ogura, Yoshitoshi; Toyoda, Atsushi; Maruyama, Fumito

2016-06-01

Intestinal microbiota are characterized by host-specific microorganisms, which have been selected through host-microbe interactions under phylogenetic evolution and transition of feeding behavior by the host. Although many studies have focused on disease-related intestinal microbiota, the origin and evolution of host-specific intestinal microbiota have not been well elucidated. Pig is the ideal mammal model to reveal the origin and evolution of host-specific intestinal microbiota because their direct wild ancestor and close phylogenetic neighbors are available for comparison. The pig has been recognized as a Lactobacillus-type animal. We analyzed the intestinal microbiota of various animals in Suidae: domestic pigs, wild boars and Red river hogs to survey the origin and evolution of Lactobacillus-dominated intestinal microbiota by metagenomic approach and following quantitative PCR confirmation. The metagenomic datasets were separated in two clusters; the wild animal cluster being characterized by a high abundance of Bifidobacterium, whereas the domesticated (or captured) animal cluster by Lactobacillus. In addition, Enterobacteriaceae were harbored as the major family only in domestic Sus scrofa. We conclude that domestication may have induced a larger Enterobacteriaceae population in pigs, and the introduction of modern feeding system further caused the development of Lactobacillus-dominated intestinal microbiota, with genetic and geographical factors possibly having a minor impact. © 2015 Japanese Society of Animal Science.

Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs.

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Craig J Bierle

Full Text Available Primary Zika virus (ZIKV infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development.

Risk factor profile in retinal detachment

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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.

Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

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Welling JD

2012-04-01

Full Text Available John D Welling, Ahmad B Tarabishy, John ChristoforidisDepartment of Ophthalmology, Havener Eye Institute, Ohio State University, Columbus, OH, USAAbstract: Cytomegalovirus (CMV retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants.Keywords: cytomegalovirus retinitis, central retinal vein occlusion, immunosuppression, solid organ transplant, venous stasis, risk factor

WIDEFIELD SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING OF PERIPHERAL ROUND RETINAL HOLES WITH OR WITHOUT RETINAL DETACHMENT.

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Casswell, Edward J; Abou Ltaif, Sleiman; Carr, Thomas; Keane, Pearse A; Charteris, David G; Wickham, Louisa

2018-03-02

To describe the widefield spectral-domain optical coherence tomography features of peripheral round retinal holes, with or without associated retinal detachment (RD). Retrospective, observational study of 28 eyes with peripheral round retinal holes, with and without RD. Patients underwent imaging with a widefield 50-degree spectral-domain optical coherence tomography (Heidelberg Engineering, Germany) and Optos ultra-widefield imaging systems (Optos, United Kingdom). Vitreous attachment at the site of the retinal hole was detected in 27/28 (96.4%) cases. Cases were split into three groups: RHs with RD (n = 12); RHs with subretinal fluid (n = 5), and flat RHs (n = 11), with minimal or no subretinal fluid. 91.6% retinal holes associated with subretinal fluid or RD had vitreous attachment at the site of the hole. Eighty percent had vitreous attachment at both edges of the retinal hole, in a U-shape configuration, which appeared to exert traction. By contrast, flat retinal holes had visible vitreous attachment only at one edge of the retinal hole in 45.4%. Vitreous attachment was commonly seen at the site of round retinal holes. Vitreous attachment at both edges of the retinal hole in a U-shape configuration was more commonly seen at holes associated with subretinal fluid or RD.

Retinal vessels caliber assessment in patients with arterial hypertension

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N. S. Semenova

2014-07-01

Full Text Available Purpose: to evaluate the diagnostic capability of automated retinal vessels (RV caliber estimation for hypertensive angiopathy.Methods: this study included 146 patients (292 eyes with arterial hypertension. All the subjects underwent fundus photography and RV caliber estimation. the latter was performed using newly developed computer-based method for automated vessel detection and central retinal arteriolar and venular equivalents determination (CRAE & CRVE. Sensitivity, specificity, and reproducibility of the method were estimated.Results: the method of RV caliber assessment showed good reproducibility. the overall specificity and sensitivity were 74% and 80.77%, respectively. Computer-based method of retinal vascular caliber assessment revealed higher predictive value comparing with ophthalmoscopic assessment (AUC = 0.903 and 0.85, respectively. Retinal arteriolar and venular caliber and AVR tend to decrease with age. Higher blood pressure is associated with narrower retinal arterioles.Conclusion: Novel method of RV caliber estimation demonstrated high information value. these findings are in good agreementwith data from major population-based studies.

Retinal vessels caliber assessment in patients with arterial hypertension

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N. S. Semenova

2012-01-01

Full Text Available Purpose: to evaluate the diagnostic capability of automated retinal vessels (RV caliber estimation for hypertensive angiopathy.Methods: this study included 146 patients (292 eyes with arterial hypertension. All the subjects underwent fundus photography and RV caliber estimation. the latter was performed using newly developed computer-based method for automated vessel detection and central retinal arteriolar and venular equivalents determination (CRAE & CRVE. Sensitivity, specificity, and reproducibility of the method were estimated.Results: the method of RV caliber assessment showed good reproducibility. the overall specificity and sensitivity were 74% and 80.77%, respectively. Computer-based method of retinal vascular caliber assessment revealed higher predictive value comparing with ophthalmoscopic assessment (AUC = 0.903 and 0.85, respectively. Retinal arteriolar and venular caliber and AVR tend to decrease with age. Higher blood pressure is associated with narrower retinal arterioles.Conclusion: Novel method of RV caliber estimation demonstrated high information value. these findings are in good agreementwith data from major population-based studies.

Development of real-time PCR and hybridization methods for detection and identification of thermophilic Campylobacter spp. in pig faecal samples

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Jensen, Annette Nygaard; Andersen, M. T.; Dalsgaard, Anders

2005-01-01

species-specific detection of Campylobacter spp. in naturally infected pig faecal samples after an enrichment step, whereas the hybridization approach enhanced the specific isolation of C. jejuni (present in minority to C. coli) from pigs. Conclusions: The rt-PCR was specific for Campylobacter jejuni, C...... by phenotypic methods and the developed rt-PCR provides an easy and fast method for such differentiation. Detection of C. jejuni by colony hybridization may increase the isolation rate of this species from pig faeces....

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

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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.

Measurements of the degree of development of rigor mortis as an indicator of stress in slaughtered pigs.

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Warriss, P D; Brown, S N; Knowles, T G

2003-12-13

The degree of development of rigor mortis in the carcases of slaughter pigs was assessed subjectively on a three-point scale 35 minutes after they were exsanguinated, and related to the levels of cortisol, lactate and creatine kinase in blood collected at exsanguination. Earlier rigor development was associated with higher concentrations of these stress indicators in the blood. This relationship suggests that the mean rigor score, and the frequency distribution of carcases that had or had not entered rigor, could be used as an index of the degree of stress to which the pigs had been subjected.

Hmga2 regulates self-renewal of retinal progenitors.

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Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

2014-11-01

In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

Smallholder Pig Marketing Systems in the Southern Highlands of Tanzania

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Kimbi, Eliakunda C.; Mlangwa, James; Thamsborg, Stig Milan

2016-01-01

A study using two cross-sectional and a longitudinal research designs was undertaken to assess smallholder pig marketing system to explore basic information for improving smallholder pig production and marketing systems. The first design involved a cross-sectional survey of 300 pig farmers randomly...... by informal marketing channels, hence, limit the effectiveness of pig production and marketing. Marketed pigs had smaller weights compared to their ages, therefore contributing to poor returns to pig farmers and sub-optimal pork market supply. The study recommends strategic development of pig value chain...... villages who had also participated in the first design. Results showed that, pig-marketing systems had various channels and segments moving mainly pigs and pork to farmers, traders and consumers. Major market participants in the pig market chain were the pig farmers who played a dual role as pig producers...

The microRNA, miR-29c, participates in muscle development through targeting the YY1 gene and is associated with postmortem muscle pH in pigs

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Weiya ZHANG,Wei WEI,Yuanyuan ZHAO,Shuhong ZHAO,Xinyun LI

2015-12-01

Full Text Available Previous studies indicated that miR-29c is important for muscle development in mice and human, but its role in pigs is unknown. In this study, we detected the expression of miR-29c in Meishan longissimus lumborum (LL muscle. The results showed that miR-29c was gradually upregulated during development of skeletal muscle in pig. Moreover, the expression of YY1 and Akt3 genes, which were confirmed to be targeted by miR-29c in mice, was decreased along with muscle development. Furthermore, the expression level of miR-29c was significantly higher in adult Meishan pigs than Large White pigs, while the expression of YY1 and Akt3 genes was significantly lower in Meishan pigs. These results indicated that the expression pattern of miR-29c was opposite to that of YY1 and Akt3 genes in pigs. Also, the luciferase assay indicated that miR-29s can target the YY1 gene in pigs. In addition, we identified a T to C mutation in the primary transcript of miR-29c, which was associated with the postmortem muscle pH in pigs. Based on these results, we concluded that miR-29c is also important in skeletal muscle development of pigs.

Effect of pharmacologically induced retinal degeneration on retinal autofluorescence lifetimes in mice.

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Dysli, Chantal; Dysli, Muriel; Zinkernagel, Martin S; Enzmann, Volker

2016-12-01

Fluorescence lifetime imaging ophthalmoscopy (FLIO) was used to investigate retinal autofluorescence lifetimes in mouse models of pharmacologically induced retinal degeneration over time. Sodium iodate (NaIO 3 , 35 mg/kg intravenously) was used to induce retinal pigment epithelium (RPE) degeneration with subsequent loss of photoreceptors (PR) whereas N-methyl-N-nitrosourea (MNU, 45 mg/kg intraperitoneally) was employed for degeneration of the photoreceptor cell layer alone. All mice were measured at day 3, 7, 14, and 28 after the respective injection of NaIO 3 , MNU or NaCl (control). Fluorescence lifetime imaging was performed using a fluorescence lifetime imaging ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany). Fluorescence was excited at 473 nm and fluorescence lifetimes were measured in a short and a long spectral channel (498-560 nm and 560-720 nm). Corresponding optical coherence tomography (OCT) images were consecutively acquired and histology was performed at the end of the experiments. Segmentation of OCT images and histology verified the cell type-specific degeneration process over time. Retinal autofluorescence lifetimes increased from day 3 to day 28 in mice after NaIO 3 treatment. Finally, at day 28, fluorescence lifetimes were prolonged by 8% in the short and 61% in the long spectral channel compared to control animals (p = 0.21 and p = 0.004, respectively). In mice after MNU treatment, the mean retinal autofluorescence lifetimes were already decreased at day 3 and retinal lifetimes were finally shortened by 27% in the short and 51% in the long spectral channel at day 28 (p = 0.0028). In conclusion, degeneration of the RPE with subsequent photoreceptor degeneration by NaIO 3 lead to longer mean fluorescence lifetimes of the retina compared to control mice, whereas during specific degeneration of the photoreceptor layer induced by MNU shorter lifetimes were measured. Therefore, short retinal fluorescence lifetimes may originate

Peripheral Retinal Vascular Patterns in Patients with Rhegmatogenous Retinal Detachment in Taiwan.

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San-Ni Chen

Full Text Available This is an observational study of fluorescein angiography (FA in consecutive patients with rhegmatogenous retinal detachment (RRD in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL, and refraction status (RF recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8% in group 1, 3 eyes (4.1% in group 2, 40 eyes (54.8% in group 3 and 17 eyes (23.3% in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion.

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

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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.

Development of large intestinal attaching and effacing lesions in pigs in association with the feeding of a particular diet.

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Neef, N A; McOrist, S; Lysons, R J; Bland, A P; Miller, B G

1994-10-01

Hysterotomy-derived piglets were kept in gnotobiotic isolators and artificially colonized at 7 days of age with an adult bovine enteric microflora. At 3 weeks of age, the pigs were transferred to conventional experimental accommodation and weaned, either onto a solid diet that had been associated with field cases of typhlocolitis in pigs or onto a solid control diet. At necropsy at 5 weeks of age, groups of pigs fed the diet associated with field cases of typhlocolitis were found to have developed typhlocolitis. This was absent from the groups fed the control diet. The typhlocolitis was characterized by attaching and effacing lesions typical of those described following experimental inoculation of various species with enteropathogenic Escherichia coli. A nonverocytotoxic, eae probe-positive E. coli serotype O116 was isolated from pigs on the colitis-associated diet but not from any of the pigs on the control diet. Coliform bacteria attached to the colonic lesions reacted with polyclonal antiserum to E. coli O116 in an immunoperoxidase assay of histological sections of affected tissue. No reaction with this antiserum was observed in corresponding tissue sections taken from pigs on the control diet. No colon lesions were observed in germfree pigs fed either of the diets. It is postulated that proliferation and possibly expression of pathogenicity of the attaching and effacing E. coli responsible for the lesions are strongly influenced by diet.

Pharmacology of Myopia and Potential Role for Intrinsic Retinal Circadian Rhythms

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Stone, Richard A.; Pardue, Machelle T.; Iuvone, P. Michael; Khurana, Tejvir S.

2013-01-01

Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetycholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine’s role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude

Advances in Retinal Stem Cell Biology

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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.

Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development.

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Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J; Rutland, Catrin S

2014-01-01

The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8-12 months and life expectancy is ∼5-6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0-1 month, 1-3 months, 3-6 months, 6 months-1 year and 1-4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have

Sector retinitis pigmentosa.

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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.

Applications of CRISPR/Cas9 in retinal degenerative diseases

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Peng, Ying-Qian; Tang, Luo-Sheng; Yoshida, Shigeo; Zhou, Ye-Di

2017-01-01

Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs). In this review, we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also emphasize the potential applications of this technique in treating retinal degenerative diseases. PMID:28503441

Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening.

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Sobacı, Güngör; Ozge, Gökhan; Gündoğan, Fatih Ç

2012-01-01

To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port(®) system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = -0.55, P = 0.004, r = 0.68, P = 0.001, r = -0.65, P = 0.001, and r = -0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system.

Subretinal posterior pole injury induces selective proliferation of RPE cells in the periphery in in vivo studies in pigs

DEFF Research Database (Denmark)

Kiilgaard, Jens Folke; Prause, Jan U; Prause, Michala

2007-01-01

PURPOSE: To study topographical differences in porcine retinal pigment epithelial (RPE) cell proliferation (1) in vivo, after experimental central surgical subretinal injury, and (2) in vitro. METHODS: Domestic pigs underwent either experimental RPE debridement (n = 5), subretinal amniotic membrane...... cells. This observation was true of both types of experimental surgery performed. In vitro, RPE isolates from the pre-equatorial region consistently yielded higher cell densities than did RPE cell isolates from more central parts of the epithelium. This was apparent through the three first passages...

A characteristic phenotypic retinal appearance in Norrie disease.

Science.gov (United States)

Drenser, Kimberly A; Fecko, Alice; Dailey, Wendy; Trese, Michael T

2007-02-01

To describe a striking retinal finding that the authors have only seen in Norrie disease eyes and to determine if a particular genotype corresponds to this dramatic presentation. This is a retrospective, interventional case report of four patients seen in the clinic over a 1-year period. All patients had analysis of the Norrie gene by direct sequencing. All patients presented with a similar retinal appearance of dense stalk tissue, globular dystrophic retina, and peripheral avascular retina with pigmentary changes. Each patient was found to have a mutation in the Norrie gene affecting a cystine residue in the cystine knot domain. The mutations are predicted to disrupt the structure of the protein product, norrin, which is required for activation of the Wnt receptor:beta-catenin pathway. No other vitreoretinopathy that the authors have seen demonstrates this characteristic retinal presentation of severe retinal dysplasia. All four patients were found to have mutations in the Norrie gene which alter the cystine knot motif. Mutations affecting this domain appear to have devastating effects on retinal development and indicate phenotype correlates with mutations affecting the cystine knot domain.

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.

Effect of internal limiting membrane peeling on the development of epiretinal membrane after pars plana vitrectomy for primary rhegmatogenous retinal detachment.

Science.gov (United States)

Nam, Ki Yup; Kim, Jung Yeul

2015-05-01

To investigate the difference in the occurrence of postoperative epiretinal membranes (ERMs) in vitrectomy for rhegmatogenous retinal detachment with and without peeling of the internal limiting membrane (ILM). The medical records of the 135 patients, who underwent vitrectomy for primary rhegmatogenous retinal detachment from November 2007 to August 2011, were analyzed retrospectively. Of the subjects, 70 patients underwent ILM peeling during the surgery and 65 did not. The best-corrected visual acuity, fundus photograph, and optical coherence tomography were collected 3, 6, and 12 months postoperatively. The relationship between ILM peeling and the preoperative findings of rhegmatogenous retinal detachment and development of a postoperative ERM was analyzed. No ERM occurred in the ILM peeling group, whereas an ERM occurred in 14 of 65 patients who underwent vitrectomy without ILM peeling (21.5%). This difference was significant (P peeling group and was significantly higher 12 months postoperatively (P = 0.03). Internal limiting membrane peeling seems to prevent the occurrence of a postoperative ERM in patients with primary rhegmatogenous retinal detachment.

Retinal Detachment

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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

Peripapillary retinal thermal coagulation following electrical injury

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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.

Automatic detection and classification of malarial retinopathy- associated retinal whitening in digital retinal images

International Nuclear Information System (INIS)

Akram, M.U.; Alvi, A.B.N.; Khan, S.A.

2017-01-01

Malarial retinopathy addresses diseases that are characterized by abnormalities in retinal fundus imaging. Macular whitening is one of the distinct signs of cerebral malaria but has hardly been explored as a critical bio-marker. The paper proposes a computerized detection and classification method for malarial retinopathy using retinal whitening as a bio-marker. The paper combines various statistical and color based features to form a sound feature set for accurate detection of retinal whitening. All features are extracted at image level and feature selection is performed to detect most discriminate features. A new method for macula location is also presented. The detected macula location is further used for grading of whitening as macular or peripheral whitening. Support vector machine along with radial basis function is used for classification of normal and malarial retinopathy patients. The evaluation is performed using a locally gathered dataset from malarial patients and it achieves an accuracy of 95% for detection of retinal whitening and 100% accuracy for grading of retinal whitening as macular or non-macular. One of the major contributions of proposed method is grading of retinal whitening into macular or peripheral whitening. (author)

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

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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

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

Retinitis pigmentosa, Coats disease and uveitis.

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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.

Live-cell imaging: new avenues to investigate retinal regeneration

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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.

Retinitis pigmentosa: genes and disease mechanisms.

Science.gov (United States)

Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Ponzin, Diego; Sorrentino, Francesco S; Parmeggiani, Francesco

2011-06-01

Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.

Alterations of sodium and potassium channels of RGCs in RCS rat with the development of retinal degeneration.

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Chen, Zhongshan; Song, Yanping; Yao, Junping; Weng, Chuanhuang; Yin, Zheng Qin

2013-11-01

All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.

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

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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.

Regulation of Taurine transporter activity in cultured rat retinal ganglion cells and rat retinal Muller Cells

International Nuclear Information System (INIS)

Eissa, Laila A.; Smith, Sylvia B.; El-sherbeny, Amira A.

2006-01-01

Diabetic retinopathy is one of the most common complications of diabetes. The amino acid taurine is believed to play an antioxidant protective role in diabetic retinopathy through the scavenging of the reactive species. It is not well established whether taurine uptake is altered in retina cells during diabetic conditions. Thus, the present study was designed to investigate the changes in taurine transport in cultures of rat retinal Muller cells and rat retinal ganglion cells under conditions associated with diabetes. Taurine was abundantly taken up by retinal Muller cells and rat retinal ganglion cells under normal glycemic condition. Taurine was actively transported to rat Muller cells and rat retinal ganglion cells in a Na and Cl dependant manner. Taurine uptake further significantly elevated in both type of cells after the incubation with high glucose concentration. This effect could be attributed to the increase in osmolarity. Because Nitric Oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we also determined the activity of taurine transporter in cultured rat retinal Muller cells and rat retinal ganglion cells in the presence of the NO donors, SIN-1 and SNAP. Taurine uptake was elevated above control value after 24-h incubation with low concentration of NO donors. We finally investigated the ability of neurotoxic glutamate to change taurine transporter activity in both types of cells. Uptake of taurine was significantly increased in rat retinal ganglion cells when only incubated with high concentration of glutamate. Our data provide evidence that taurine transporter is present in cultured rat retinal ganglion and Muller cells and is regulated by hyperosmolarity. The data are relevant to disease such as diabetes and neuronal degeneration where retinal cell volume may dramatically change. (author)

Outcomes in bullous retinal detachment

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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.

Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus.

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Kelly E O'Quin

Full Text Available The retina is the light-sensitive tissue of the eye that facilitates vision. Mutations within genes affecting eye development and retinal function cause a host of degenerative visual diseases, including retinitis pigmentosa and anophthalmia/microphthalmia. The characin fish Astyanax mexicanus includes both eyed (surface fish and eyeless (cavefish morphs that initially develop eyes with normal retina; however, early in development, the eyes of cavefish degenerate. Since both surface and cave morphs are members of the same species, they serve as excellent evolutionary mutant models with which to identify genes causing retinal degeneration. In this study, we crossed the eyed and eyeless forms of A. mexicanus and quantified the thickness of individual retinal layers among 115 F(2 hybrid progeny. We used next generation sequencing (RAD-seq and microsatellite mapping to construct a dense genetic map of the Astyanax genome, scan for quantitative trait loci (QTL affecting retinal thickness, and identify candidate genes within these QTL regions. The map we constructed for Astyanax includes nearly 700 markers assembled into 25 linkage groups. Based on our scans with this map, we identified four QTL, one each associated with the thickness of the ganglion, inner nuclear, outer plexiform, and outer nuclear layers of the retina. For all but one QTL, cavefish alleles resulted in a clear reduction in the thickness of the affected layer. Comparative mapping of genetic markers within each QTL revealed that each QTL corresponds to an approximately 35 Mb region of the zebrafish genome. Within each region, we identified several candidate genes associated with the function of each affected retinal layer. Our study is the first to examine Astyanax retinal degeneration in the context of QTL mapping. The regions we identify serve as a starting point for future studies on the genetics of retinal degeneration and eye disease using the evolutionary mutant model Astyanax.

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

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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.

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.

Effect of fenbendazole in water on pigs infected with Ascaris suum in finishing pigs under field conditions.

Science.gov (United States)

Lassen, Brian; Oliviero, Claudio; Orro, Toomas; Jukola, Elias; Laurila, Tapio; Haimi-Hakala, Minna; Heinonen, Mari

2017-04-15

The husbandry of pigs for meat production is a constantly developing industry. Most studies on the effects of Ascaris suum infection in pigs and its prevention with anthelmintics are over a decade old. We examined the effect of 2.5mg fenbendazole per kg bodyweight administered in drinking water for two consecutive days on A. suum infection 1 and 6 weeks after pigs arrived to fattening units. We hypothesised that the treatment would reduce the presence of A. suum-infections, improve the average daily weight gain of pigs, reduce the percentage of liver rejections in pens by 50% and increase the lean meat percentage at slaughter by 1%. The study included a placebo group (427 pigs) and a treatment group (420 pigs) spanning four different farms previously reporting ≥15% liver rejection. The treatment was given for 2 consecutive days 1 and 6 weeks after the pigs arrived to the fattening unit. Faecal samples were collected during weeks 1, 6 and 12 from all pigs and examined for A. suum eggs. Blood was collected during weeks 1 and 12 from a subgroup of the pigs and examined for anti-A. suum antibodies and clinical blood parameters. Data on liver rejection and lean meat percentage were collected post-mortem. The proportion of Ascaris seropositive pigs changed from 8.6% to 22.2% and 20.3% to 16.3% in the placebo and treatment group respectively. Fenbendazole reduced the presence of A. suum eggs in faeces the percentage of liver rejections by 69.8%. The treatment did not affect daily weight gain or lean meat percentage. Pigs with A. suum eggs in faeces at week 6 had a lower average daily weight gain of 61.8g/day compared with pigs without parasite eggs. Fenbendazole treatment may be a useful option for farms struggling with persistent A. suum problems and demonstrate a beneficial effect on the weight gain of the animals shedding eggs in faeces and result in fewer condemned livers at slaughter. Copyright © 2017 Elsevier B.V. All rights reserved.

Bilateral Simultaneous Rhegmatogenous Retinal Detachment following Laser in situ Keratomileusis

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Erhan Yumusak

2016-06-01

Full Text Available A 21-year-old woman developed simultaneous rhegmatogenous retinal detachment after laser in situ keratomileusis (LASIK in both eyes. She underwent pars plana vitrectomy surgery combined with endolaser photocoagulation and silicone oil tamponade in the right eye. A week later, pneumatic retinopexy was done in the left eye. As the retinal tear did not seal, 360° scleral buckling surgery was performed and retina was attached. Bilateral simultaneous rhegmatogenous retinal detachment after LASIK for correction of myopia can be a serious complication. Patients should be informed about the possibility of this complication.

Prolactin family of the guinea pig, Cavia porcellus.

Science.gov (United States)

Alam, S M Khorshed; Konno, Toshihiro; Rumi, M A Karim; Dong, Yafeng; Weiner, Carl P; Soares, Michael J

2010-08-01

Prolactin (PRL) is a multifunctional hormone with prominent roles in regulating growth and reproduction. The guinea pig (Cavia porcellus) has been extensively used in endocrine and reproduction research. Thus far, the PRL cDNA and protein have not been isolated from the guinea pig. In the present study, we used information derived from the public guinea pig genome database as a tool for identifying guinea pig PRL and PRL-related proteins. Guinea pig PRL exhibits prominent nucleotide and amino acid sequence differences when compared with PRLs of other eutherian mammals. In contrast, guinea pig GH is highly conserved. Expression of PRL and GH in the guinea pig is prominent in the anterior pituitary, similar to known expression patterns of PRL and GH for other species. Two additional guinea pig cDNAs were identified and termed PRL-related proteins (PRLRP1, PRLRP2). They exhibited a more distant relationship to PRL and their expression was restricted to the placenta. Recombinant guinea pig PRL protein was generated and shown to be biologically active in the PRL-responsive Nb2 lymphoma cell bioassay. In contrast, recombinant guinea pig PRLRP1 protein did not exhibit PRL-like bioactivity. In summary, we have developed a new set of research tools for investigating the biology of the PRL family in an important animal model, the guinea pig.

Platform image processing to study the structural properties of retinal vessel

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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. 

Effect of fenbendazole in water on pigs infected with Ascaris suum in finishing pigs under field conditions

DEFF Research Database (Denmark)

Lassen, Brian; Oliviero, Claudio; Orro, Toomas

2017-01-01

The husbandry of pigs for meat production is a constantly developing industry. Most studies on the effects of Ascaris suum infection in pigs and its prevention with anthelmintics are over a decade old. We examined the effect of 2.5 mg fenbendazole per kg bodyweight administered in drinking water...... post-mortem. The proportion of Ascaris seropositive pigs changed from 8.6% to 22.2% and 20.3% to 16.3% in the placebo and treatment group respectively. Fenbendazole reduced the presence of A. suum eggs in faeces the percentage of liver rejections by 69.8%. The treatment did not affect daily weight gain...... or lean meat percentage. Pigs with A. suum eggs in faeces at week 6 had a lower average daily weight gain of 61.8 g/day compared with pigs without parasite eggs. Fenbendazole treatment may be a useful option for farms struggling with persistent A. suum problems and demonstrate a beneficial effect...

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

Smallholder pig production

DEFF Research Database (Denmark)

Braae, Uffe Christian; Ngowi, Helena; Johansen, Maria Vang

2013-01-01

A cross-sectional study was carried out in the Mbeya Region, Tanzania, with the aim of describing the distribution and diversity of ectoparasites on pigs, within confinement and free-range production systems of smallholder farms. A total of 128 farms were surveyed, with 96 practising confinement...... and 32 practising free-range production systems. The prevalence of ectoparasites on pigs within confinement and free-range production systems was 24% and 84%, respectively. Logistic regression analyses revealed that keeping pigs in a free-range system and the presence of neighbouring pigs were risk...... although highly prevalent within both production systems. Keeping pigs in a free-range system and contact with neighbouring pigs were main risk factors for the presence of ectoparasites. Confinement was highly effective as a preventive tool against hard ticks....

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

Directory of Open Access Journals (Sweden)

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.

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- ...

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.

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.

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

Retinal Macroglial Responses in Health and Disease

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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.

Regulation of adpose tissue development ion the fetus: the fetal pig model

International Nuclear Information System (INIS)

Hausman, G.J.; Campion, D.R.; Martin, R.J.

1986-01-01

We have examined genetic, endocrine, nutritional and neural influences on metabolic and structural differentiation of the fetal pig subcutaneous depot. As in man, the subcutaneous depot in the pig is the largest depot of the body; it is similar anatomically in both species. Studies of fetuses from genetically lean and obese sows illustrate the full utility of the fetal pig model. The following measurements have been obtained from fetuses (110 days of gestation) from lean and obese sows: adipocyte size and number, lipoprotein lipase (LPL) and other lipogenic enzyme activities, radiolabelled substrate flux studies of lipid metabolism, enzyme histochemistry of lipogenic enzymes, body composition, levels of plasma hormones and metabolites and lipid clearance values. Of these measurements, an elevated fat cell LPL activity and depressed plasma growth hormone level were the most important abnormalities in obese fetuses. Experimentally induced alterations in the fetal endocrine profile have shown that pituitary associated hormones may control fetal adipocyte replication; whereas, pancreatic hormones may control adipocyte hypertrophy and maturation. Studies of the fetal pig should lead to identification of specific factors responsible for adipocyte abnormalities of obesity

Knockdown of Zebrafish Blood Vessel Epicardial Substance Results in Incomplete Retinal Lamination

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Yu-Ching Wu

2014-01-01

Full Text Available Cell polarity during eye development determines the normal retinal lamination and differentiation of photoreceptor cells in the retina. In vertebrates, blood vessel epicardial substance (Bves is known to play an important role in the formation and maintenance of the tight junctions essential for epithelial cell polarity. In the current study, we generated a transgenic zebrafish Bves (zbves promoter-EGFP zebrafish line to investigate the expression pattern of Bves in the retina and to study the role of zbves in retinal lamination. Immunostaining with different specific antibodies from retinal cells and transmission electron microscopy were used to identify the morphological defects in normal and Bves knockdown zebrafish. In normal zebrafish, Bves is located at the apical junctions of embryonic retinal neuroepithelia during retinogenesis; later, it is strongly expressed around inner plexiform layer (IPL and retinal pigment epithelium (RPE. In contrast, a loss of normal retinal lamination and cellular polarity was found with undifferentiated photoreceptor cells in Bves knockdown zebrafish. Herein, our results indicated that disruption of Bves will result in a loss of normal retinal lamination.

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

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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.

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.

Vision from next generation sequencing: multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease.

Science.gov (United States)

Yang, Hyun-Jin; Ratnapriya, Rinki; Cogliati, Tiziana; Kim, Jung-Woong; Swaroop, Anand

2015-05-01

Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of "gene" itself has become ambiguous, and the central dogma is continuously being revised and expanded. Computational biology and computational medicine are no longer intellectual domains of the chosen few. Next generation sequencing (NGS) technology, together with novel methods of pattern recognition and network analyses, has revolutionized the way we think about fundamental biological mechanisms and cellular pathways. In this review, we discuss NGS-based genome-wide approaches that can provide deeper insights into retinal development, aging and disease pathogenesis. We first focus on gene regulatory networks (GRNs) that govern the differentiation of retinal photoreceptors and modulate adaptive response during aging. Then, we discuss NGS technology in the context of retinal disease and develop a vision for therapies based on network biology. We should emphasize that basic strategies for network construction and analyses can be transported to any tissue or cell type. We believe that specific and uniform guidelines are required for generation of genome, transcriptome and epigenome data to facilitate comparative analysis and integration of multi-dimensional data sets, and for constructing networks underlying complex biological processes. As cellular homeostasis and organismal survival are dependent on gene-gene and gene-environment interactions, we believe that network-based biology will provide the foundation for deciphering disease mechanisms and discovering novel drug targets for retinal neurodegenerative diseases. Published by Elsevier Ltd.

Analyzing Protein Changes in Guinea Pig Tissue Lysates Using Non-guinea Pig Specific Antibodies: Procedures for Western Blotting and Examples Using 16 Individual Antibodies for Common CNS Proteins

Science.gov (United States)

2006-05-01

guinea pig model does present a significant problem...trying to correlate behavioral and protein changes due to the absence of guinea pig -specific antibodies. We...have developed a procedure to determine the specificity of commercially available, non- guinea pig -specific antibodies in guinea pig lysates.

Breeding objectives for pigs in Kenya. I: bio-economic model development and application to smallholder production systems.

Science.gov (United States)

Mbuthia, Jackson M; Rewe, Thomas O; Kahi, Alexander K

2015-02-01

A deterministic bio-economic model was developed and applied to evaluate biological and economic variables that characterize smallholder pig production systems in Kenya. Two pig production systems were considered namely, semi-intensive (SI) and extensive (EX). The input variables were categorized into biological variables including production and functional traits, nutritional variables, management variables and economic variables. The model factored the various sow physiological systems including gestation, farrowing, lactation, growth and development. The model was developed to evaluate a farrow to finish operation, but the results were customized to account for a farrow to weaner operation for a comparative analysis. The operations were defined as semi-intensive farrow to finish (SIFF), semi-intensive farrow to weaner (SIFW), extensive farrow to finish (EXFF) and extensive farrow to weaner (EXFW). In SI, the profits were the highest at KES. 74,268.20 per sow per year for SIFF against KES. 4026.12 for SIFW. The corresponding profits for EX were KES. 925.25 and KES. 626.73. Feed costs contributed the major part of the total costs accounting for 67.0, 50.7, 60.5 and 44.5 % in the SIFF, SIFW, EXFF and EXFW operations, respectively. The bio-economic model developed could be extended with modifications for use in deriving economic values for breeding goal traits for pigs under smallholder production systems in other parts of the tropics.

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...

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

Lattice degeneration of the retina and retinal detachment.

Science.gov (United States)

Semes, L P

1992-01-01

Lattice retinal degeneration is considered the most significant peripheral retinal disorder potentially predisposing to retinal breaks and retinal detachment. Lattice degeneration affects the vitreous and inner retinal layers with secondary changes as deep as the retinal pigment epithelium and perhaps the choriocapillaris. Variations in clinical appearance are the rule; geographically, lattice lesions favor the vertical meridians between the equator and the ora serrata. Lattice degeneration begins early in life and has been reported in sequential generations of the same family. Along with its customary bilateral occurrence, lattice shares other characteristics of a dystrophy. The association between the vitreous and retina in lattice lesions may be responsible for the majority of lattice-induced retinal detachments. The tumultuous event of posterior vitreous separation in the presence of abnormally strong vitreoretinal adherence is the trigger for a retinal tear that, in turn, may lead to retinal detachment. Although retinal holes in young patients with lattice degeneration may play a role in the evolution of retinal detachment, the clinical course of lattice degeneration seems to be one of dormancy rather than of progressive change. This discussion outlines the pathophysiology of lattice retinal degeneration and the relationship of pathophysiology to clinical presentation. The epidemiology of lattice degeneration is summarized, as are the possible precursors to retinal detachment. A clinical characterization of the natural history of lattice degeneration is offered, and interventions for complications are described. To conclude, management strategies from a primary-care standpoint are reviewed.

Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

Science.gov (United States)

Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

2017-02-01

It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

Science.gov (United States)

Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

2011-01-01

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

Bilateral acute retinal necrosis-A case report

Directory of Open Access Journals (Sweden)

Prasad Palimar

1992-01-01

Full Text Available A 42 year old man presented with acute bilateral uveitis and necrotizing retinitis. Systemic investigations including test for AIDS and CMV retinitis were negative. Despite oral Acyclovir, both eyes progressed rapidly to retinal detachment with loss of vision. Early recognition is necessary to diagnose the bilateral acute retinal necrosis syndrome and initiate treatment. Bilateral acute retinal necrosis (BARN is a term first coined by Young and Bird in 1978 although the syndrome had been originally described by Urayama et al as an unilateral condition. This syndrome is characterized by the triad of acute confluent peripheral necrotizing retinitis, moderate to severe vasculitis and vitritis in an otherwise healthy individual. Rhegmatogenous retinal detachment occurs within two to three months of the onset of the disease and the second eye is involved in 36% of patients, usually within 6 weeks. We herein report a patient who presented with simultaneous BARN leading to retinal detachment in a matter of days. Also, to our knowledge this is the first report of this condition in India.

INTERNAL LIMITING MEMBRANE PEELING-DEPENDENT RETINAL STRUCTURAL CHANGES AFTER VITRECTOMY IN RHEGMATOGENOUS RETINAL DETACHMENT.

Science.gov (United States)

Hisatomi, Toshio; Tachibana, Takashi; Notomi, Shoji; Koyanagi, Yoshito; Murakami, Yusuke; Takeda, Atsunobu; Ikeda, Yasuhiro; Yoshida, Shigeo; Enaida, Hiroshi; Murata, Toshinori; Sakamoto, Taiji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2018-03-01

To examine retinal changes after vitrectomy with internal limiting membrane (ILM) peeling, we used 3-dimensional optical coherence tomography (3D-OCT) in rhegmatogenous retinal detachment cases. The 68 eyes from 67 patients with rhegmatogenous retinal detachment were studied, including 35 detached macula cases (51%) and 33 attached macula cases. Internal limiting membrane peeling was performed with fine forceps after brilliant blue G staining. The 3D-OCT images were obtained with volume-rendering technologies from cross-sectional OCT images. The 3D-OCT detected 45 eyes (66%) with ILM peeling-dependent retinal changes, including dissociated optic nerve fiber layer appearance, dimple sign, temporal macular thinning, ILM peeling area thinning, or forceps-related retinal thinning. The ILM peeled area was detectable in only 9 eyes with 3D-OCT, whereas it was undetectable in other 59 eyes. The dissociated optic nerve fiber layer appearance was detected in 8 of the total cases (12%), and dimple signs were observed in 14 cases (21%). Forceps-related thinning was also noted in eight cases (24%) of attached macula cases and in four cases (11%) of detached macula cases. No postoperative macular pucker was noted in the observational period. The 3D-OCT clearly revealed spatial and time-dependent retinal changes after ILM peeling. The changes occurred in 2 months and remained thereafter.

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,

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.

Weaning stress and gastrointestinal barrier development: Implications for lifelong gut health in pigs

Directory of Open Access Journals (Sweden)

Adam J. Moeser

2017-12-01

Full Text Available The gastrointestinal (GI barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous systems. Together they act in concert to control normal gut functions (e.g., digestion, absorption, secretion, immunity, etc. whereas at the same time provide a barrier from the hostile conditions in the luminal environment. Breakdown of these critical GI functions is a central pathophysiological mechanism in the most serious GI disorders in pigs. This review will focus on the development and functional properties of the GI barrier in pigs and how common early life production stressors, such as weaning, can alter immediate and long-term barrier function and disease susceptibility. Specific stress-related pathophysiological mechanisms responsible for driving GI barrier dysfunction induced by weaning and the implications to animal health and performance will be discussed.

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.

[Preventive treatment of retinal detachment in aphakic eyes].

Science.gov (United States)

Regnault, F; Bregeat, P

1977-01-01

We have examined 243 cases with retinal detachment occurring within 6 months following cataract surgery. In 92 of them retinal tear was due to lattice degeneration, in 66 to snail track degeneration and in 17 to equatorial degeneration. 290 other patients had preventive treatments. In this group, there were only 10 cases of retinal detachment. 9 out of 22 patients who had no preventive treatment suffered retinal detachments. There are two reasons for the occurrence of this retinal detachment in the 6 months following cataract surgery in eyes where retinal degenerations are found: (1) surgical trauma even with cryoextraction is responsible for traction of the vitreous base, (2) rapid disappearance of the hyaluronic acid in the aphakic vitreous is responsible for the degradation of the vitreous with formation of large zones of liquid vitreous. When adhesion between the vitreous and the retinal degeneration area remains, the traction is responsible for retinal tear or retinal detachment. The importance of the preventive treatment of retinal lesions prior to cataract surgery should be stressed.

Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds.

Science.gov (United States)

Kelbsch, Carina; Maeda, Fumiatsu; Lisowska, Jolanta; Lisowski, Lukasz; Strasser, Torsten; Stingl, Krunoslav; Wilhelm, Barbara; Wilhelm, Helmut; Peters, Tobias

2017-06-01

To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes. Chromatic pupillography was performed in 40 patients with advanced RP (visual acuity Chromatic pupillography demonstrated a significant decrease in outer retinal photoreceptor responses but a persisting and disinhibited intrinsic photosensitive retinal ganglion cell function in advanced RP. These phenomena may be useful as an objective marker for the efficacy of any interventional treatment for hereditary retinal diseases as well as for the selection of suitable patients for an electronic retinal implant. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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 ...

Accelerated oxygen-induced retinopathy is a reliable model of ischemia-induced retinal neovascularization.

Science.gov (United States)

Villacampa, Pilar; Menger, Katja E; Abelleira, Laura; Ribeiro, Joana; Duran, Yanai; Smith, Alexander J; Ali, Robin R; Luhmann, Ulrich F; Bainbridge, James W B

2017-01-01

Retinal ischemia and pathological angiogenesis cause severe impairment of sight. Oxygen-induced retinopathy (OIR) in young mice is widely used as a model to investigate the underlying pathological mechanisms and develop therapeutic interventions. We compared directly the conventional OIR model (exposure to 75% O2 from postnatal day (P) 7 to P12) with an alternative, accelerated version (85% O2 from P8 to P11). We found that accelerated OIR induces similar pre-retinal neovascularization but greater retinal vascular regression that recovers more rapidly. The extent of retinal gliosis is similar but neuroretinal function, as measured by electroretinography, is better maintained in the accelerated model. We found no systemic or maternal morbidity in either model. Accelerated OIR offers a safe, reliable and more rapid alternative model in which pre-retinal neovascularization is similar but retinal vascular regression is greater.

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease

Directory of Open Access Journals (Sweden)

Despina Kokona

2016-01-01

Full Text Available The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP. This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease.

Retinal dopamine mediates multiple dimensions of light-adapted vision.

Science.gov (United States)

Jackson, Chad R; Ruan, Guo-Xiang; Aseem, Fazila; Abey, Jane; Gamble, Karen; Stanwood, Greg; Palmiter, Richard D; Iuvone, P Michael; McMahon, Douglas G

2012-07-04

Dopamine is a key neuromodulator in the retina and brain that supports motor, cognitive, and visual function. Here, we developed a mouse model on a C57 background in which expression of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, is specifically disrupted in the retina. This model enabled assessment of the overall role of retinal dopamine in vision using electrophysiological (electroretinogram), psychophysical (optokinetic tracking), and pharmacological techniques. Significant disruptions were observed in high-resolution, light-adapted vision caused by specific deficits in light responses, contrast sensitivity, acuity, and circadian rhythms in this retinal dopamine-depleted mouse model. These global effects of retinal dopamine on vision are driven by the differential actions of dopamine D1 and D4 receptors on specific retinal functions and appear to be due to the ongoing bioavailability of dopamine rather than developmental effects. Together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision as well as optimal contrast detection and acuity.

Development of known-fate survival monitoring techniques for juvenile wild pigs (Sus scrofa)

Science.gov (United States)

David A. Keiter; John C. Kilgo; Mark A. Vukovich; Fred L. Cunningham; James C. Beasley

2017-01-01

Context. Wild pigs are an invasive species linked to numerous negative impacts on natural and anthropogenic ecosystems in many regions of the world. Robust estimates of juvenile wild pig survival are needed to improve population dynamics models to facilitate management of this economically and ecologically...

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Science.gov (United States)

Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

2018-02-08

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

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...

Novel method for edge detection of retinal vessels based on the model of the retinal vascular network and mathematical morphology

Science.gov (United States)

Xu, Lei; Zheng, Xiaoxiang; Zhang, Hengyi; Yu, Yajun

1998-09-01

Accurate edge detection of retinal vessels is a prerequisite for quantitative analysis of subtle morphological changes of retinal vessels under different pathological conditions. A novel method for edge detection of retinal vessels is presented in this paper. Methods: (1) Wavelet-based image preprocessing. (2) The signed edge detection algorithm and mathematical morphological operation are applied to get the approximate regions that contain retinal vessels. (3) By convolving the preprocessed image with a LoG operator only on the detected approximate regions of retinal vessels, followed by edges refining, clear edge maps of the retinal vessels are fast obtained. Results: A detailed performance evaluation together with the existing techniques is given to demonstrate the strong features of our method. Conclusions: True edge locations of retinal vessels can be fast detected with continuous structures of retinal vessels, less non- vessel segments left and insensitivity to noise. The method is also suitable for other application fields such as road edge detection.

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.

Comparative Study of Retinal Vessel Segmentation Based on Global Thresholding Techniques

Directory of Open Access Journals (Sweden)

Temitope Mapayi

2015-01-01

Full Text Available Due to noise from uneven contrast and illumination during acquisition process of retinal fundus images, the use of efficient preprocessing techniques is highly desirable to produce good retinal vessel segmentation results. This paper develops and compares the performance of different vessel segmentation techniques based on global thresholding using phase congruency and contrast limited adaptive histogram equalization (CLAHE for the preprocessing of the retinal images. The results obtained show that the combination of preprocessing technique, global thresholding, and postprocessing techniques must be carefully chosen to achieve a good segmentation performance.

NeuroPigPen: A Scalable Toolkit for Processing Electrophysiological Signal Data in Neuroscience Applications Using Apache Pig.

Science.gov (United States)

Sahoo, Satya S; Wei, Annan; Valdez, Joshua; Wang, Li; Zonjy, Bilal; Tatsuoka, Curtis; Loparo, Kenneth A; Lhatoo, Samden D

2016-01-01

The recent advances in neurological imaging and sensing technologies have led to rapid increase in the volume, rate of data generation, and variety of neuroscience data. This "neuroscience Big data" represents a significant opportunity for the biomedical research community to design experiments using data with greater timescale, large number of attributes, and statistically significant data size. The results from these new data-driven research techniques can advance our understanding of complex neurological disorders, help model long-term effects of brain injuries, and provide new insights into dynamics of brain networks. However, many existing neuroinformatics data processing and analysis tools were not built to manage large volume of data, which makes it difficult for researchers to effectively leverage this available data to advance their research. We introduce a new toolkit called NeuroPigPen that was developed using Apache Hadoop and Pig data flow language to address the challenges posed by large-scale electrophysiological signal data. NeuroPigPen is a modular toolkit that can process large volumes of electrophysiological signal data, such as Electroencephalogram (EEG), Electrocardiogram (ECG), and blood oxygen levels (SpO2), using a new distributed storage model called Cloudwave Signal Format (CSF) that supports easy partitioning and storage of signal data on commodity hardware. NeuroPigPen was developed with three design principles: (a) Scalability-the ability to efficiently process increasing volumes of data; (b) Adaptability-the toolkit can be deployed across different computing configurations; and (c) Ease of programming-the toolkit can be easily used to compose multi-step data processing pipelines using high-level programming constructs. The NeuroPigPen toolkit was evaluated using 750 GB of electrophysiological signal data over a variety of Hadoop cluster configurations ranging from 3 to 30 Data nodes. The evaluation results demonstrate that the toolkit

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

Clinically undetected retinal breaks causing retinal detachment: A review of options for management.

Science.gov (United States)

Gupta, Deepak; Ching, Jared; Tornambe, Paul E

2017-08-12

The successful detection of retinal breaks is a critical step in rhegmatogenous retinal detachment surgery in order to prevent persistent/recurrent retinal detachments. Not all retinal breaks causing retinal detachments are obvious. Retinal breaks may be obscured by opacities that are either anterior segment related, lens related, or posterior segment related. Rules to identify breaks based on subretinal fluid configuration are more difficult to apply in pseudophakic, aphakic, and scleral buckle encircled eyes-and in eyes with repeat detachments and those with proliferative vitreoretinopathy. Exudative detachments exhibit characteristic features and must be ruled out. A thorough clinical examination preoperatively is important even if a vitrectomy is planned. We review the incidence and causes of undetected breaks, along with preoperative/clinical issues that may hinder break detection. We review the literature with respect to investigative approaches and techniques that are available to the vitreoretinal surgeon when primary breaks remain clinically undetected during the preoperative examination. We broadly divide the surgical approaches into ones where the surgeon utilizes techniques to pursue actively a search for breaks versus adopting a purely speculative approach. Advantages and disadvantages of various techniques are appraised. Intuitively one might argue that an encircling scleral buckle combined with vitrectomy would give higher single operation success than pars plana vitrectomy alone because "undetected" retinal breaks would be addressed by a 360° plombage. We could not confirm this concept. Newer techniques, such as pars plana vitrectomy augmented with dye extrusion or endoscopic-assisted pars plana vitrectomy, show encouraging results. Technological advances such as intraoperative optical coherence tomography will also help to broaden the vitreoretinal surgeon's armamentarium. At this time, there is no gold standard in terms of the recommended

Portable, low-priced retinal imager for eye disease screening

Science.gov (United States)

Soliz, Peter; Nemeth, Sheila; VanNess, Richard; Barriga, E. S.; Zamora, Gilberto

2014-02-01

The objective of this project was to develop and demonstrate a portable, low-priced, easy to use non-mydriatic retinal camera for eye disease screening in underserved urban and rural locations. Existing portable retinal imagers do not meet the requirements of a low-cost camera with sufficient technical capabilities (field of view, image quality, portability, battery power, and ease-of-use) to be distributed widely to low volume clinics, such as the offices of single primary care physicians serving rural communities or other economically stressed healthcare facilities. Our approach for Smart i-Rx is based primarily on a significant departure from current generations of desktop and hand-held commercial retinal cameras as well as those under development. Our techniques include: 1) Exclusive use of off-the-shelf components; 2) Integration of retinal imaging device into low-cost, high utility camera mount and chin rest; 3) Unique optical and illumination designed for small form factor; and 4) Exploitation of autofocus technology built into present digital SLR recreational cameras; and 5) Integration of a polarization technique to avoid the corneal reflex. In a prospective study, 41 out of 44 diabetics were imaged successfully. No imaging was attempted on three of the subjects due to noticeably small pupils (less than 2mm). The images were of sufficient quality to detect abnormalities related to diabetic retinopathy, such as microaneurysms and exudates. These images were compared with ones taken non-mydriatically with a Canon CR-1 Mark II camera. No cases identified as having DR by expert retinal graders were missed in the Smart i-Rx images.

Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): Report of the Clinical Spectrum of 3 Cases.

Science.gov (United States)

Singh, Arun D; Soto, Hansell; Bellerive, Claudine; Biscotti, Charles V

2017-09-01

To report 3 cases providing insight into clinical progression of reactive retinal astrocytic tumor. The clinical, imaging, and when available, the cytologic features of 3 cases of reactive retinal astrocytic tumor (focal nodular gliosis) were reviewed. A 6-year-old female, a 49-year-old man, and a 39-year-old man each developed a white retinal mass associated with laser photocoagulation, lattice degeneration, and treatment of a presumed vascular tumor, respectively. All tumors were white, circumscribed retinal masses that tended to be associated with exudation and either initially or eventually minimal vascularity. Reactive retinal astrocytic tumor can be observed in response to a degenerative, inflammatory, or ischemic retinal insult. Such tumors may progress after therapeutic intervention.

Analyzing Protein Changes in Guinea Pig Tissue Lysates Using Non-guinea Pig Specific Antibodies: Procedures for Western Blotting and Examples Using 16 Individual Antibodies for Common CNS Proteins

National Research Council Canada - National Science Library

Johnson, Erik A; Daugherty, Kelly S

2006-01-01

... behavioral and protein changes due to the absence of guinea pig-specific antibodies. We have developed a procedure to determine the specificity of commercially available, non-guinea pig-specific antibodies in guinea pig lysates...

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

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

Social behaviour of pigs

NARCIS (Netherlands)

Park, S. Y,; Oord, R. van; Staay, F.J. van der; Nordquist, R.E.

2010-01-01

Improper social behavior development brings problems in later social life. Several time points are known to be crucial for the development and in other words, susceptible to interruptions during those time points. In conventional pigs, those time points could be categorized to three interaction

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.

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)

Induction of autoimmune abdominal aortic aneurysm in pigs

DEFF Research Database (Denmark)

Riber, Sara Schødt; Ali, Mulham; Bergseth, Sara Hveding

2017-01-01

of this study was to develop a large animal model for abdominal aortic aneurysm induction through autoimmunity by performing sheep-to-pig xenotransplantation. Methods Six pigs underwent a xenotransplantation procedure where the infrarenal porcine aorta was replaced by a decellularized sheep aorta...

[Clinical features and prognosis of retinal lattice degeneration].

Science.gov (United States)

Guo, X R

1990-07-01

110 cases (110 eyes) of retinal lattice degeneration were clinically observed and followed up for 3-8 years. Most lesions were located in the superotemporal quadrant, band-shaped, and parallel to the ora serrata. 80.9% of the lesions presented various degrees of pigmentation, 67.1% yellowish white spots, and 83.6% white lines. 32.9% of the eyes developed retinal holes. Most lattice degenerations were accompanied by vitreous degeneration and vitreoretinal traction. The disease progressed only slowly, though in a few cases it tended to expand.

The Development of an Interactive Computer-Based Training Program for Timely and Humane On-Farm Pig Euthanasia.

Science.gov (United States)

Mullins, Caitlyn R; Pairis-Garcia, Monique D; Campler, Magnus R; Anthony, Raymond; Johnson, Anna K; Coleman, Grahame J; Rault, Jean-Loup

2018-02-05

With extensive knowledge and training in the prevention, management, and treatment of disease conditions in animals, veterinarians play a critical role in ensuring good welfare on swine farms by training caretakers on the importance of timely euthanasia. To assist veterinarians and other industry professionals in training new and seasoned caretakers, an interactive computer-based training program was created. It consists of three modules, each containing five case studies, which cover three distinct production stages (breeding stock, piglets, and wean to grower-finisher pigs). Case study development was derived from five specific euthanasia criteria defined in the 2015 Common Swine Industry Audit, a nationally recognized auditing program used in the US. Case studies provide information regarding treatment history, clinical signs, and condition severity of the pig and prompt learners to make management decisions regarding pig treatment and care. Once a decision is made, feedback is provided so learners understand the appropriateness of their decision compared to current industry guidelines. In addition to training farm personnel, this program may also be a valuable resource if incorporated into veterinary, graduate, and continuing education curricula. This innovative tool represents the first interactive euthanasia-specific training program in the US swine industry and offers the potential to improve timely and humane on-farm pig euthanasia.

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...

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...

Cognitive testing of pigs (Sus scrofa) in translational biobehavioral research

DEFF Research Database (Denmark)

Kornum, Birgitte R; Knudsen, Gitte M

2011-01-01

with a higher translational value. Several brain disorders have been fully or partially modeled in the pig and this has further spurred an interest in having access to behavioral tasks for pigs, and in particular to cognitive tasks. Cognitive testing of pigs has been conducted for several years by a small group......, and would benefit from further validation. This review presents the cognitive tasks that have been developed for pigs, their validation, and their current use....

Pig models on intestinal development and therapeutics.

Science.gov (United States)

Yin, Lanmei; Yang, Huansheng; Li, Jianzhong; Li, Yali; Ding, Xueqing; Wu, Guoyao; Yin, Yulong

2017-12-01

The gastrointestinal tract plays a vital role in nutrient supply, digestion, and absorption, and has a crucial impact on the entire organism. Much attention is being paid to utilize animal models to study the pathogenesis of gastrointestinal diseases in response to intestinal development and health. The piglet has a body size similar to that of the human and is an omnivorous animal with comparable anatomy, nutritional requirements, and digestive and associated inflammatory processes, and displays similarities to the human intestinal microbial ecosystem, which make piglets more appropriate as an animal model for human than other non-primate animals. Therefore, the objective of this review is to summarize key attributes of the piglet model with which to study human intestinal development and intestinal health through probing into the etiology of several gastrointestinal diseases, thus providing a theoretical and hopefully practical, basis for further studies on mammalian nutrition, health, and disease, and therapeutics. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young piglets and humans, the piglet has been used as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Because of similarities in anatomy and physiology between pigs and mankind, more emphasises are put on how to use the piglet model for human organ transplantation research.

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

Serological evidence of hepatitis E virus infection in pigs and jaundice among pig handlers in Bangladesh.

Science.gov (United States)

Haider, N; Khan, M S U; Hossain, M B; Sazzad, H M S; Rahman, M Z; Ahmed, F; Zeidner, N S

2017-11-01

Hepatitis E virus (HEV) is the most common cause of viral hepatitis in humans. Pigs may act as a reservoir of HEV, and pig handlers were frequently identified with a higher prevalence of antibodies to HEV. The objectives of this study were to identify evidence of HEV infection in pigs and compare the history of jaundice between pig handlers and people not exposed to pigs and pork. Blood and faecal samples were collected from 100 pigs derived from three slaughterhouses in the Gazipur district of Bangladesh from January to June, 2011. We also interviewed 200 pig handlers and 250 non-exposed people who did not eat pork or handled pigs in the past 2 years. We tested the pig sera for HEV-specific antibodies using a competitive ELISA and pig faecal samples for HEV RNA using real-time RT-PCR. Of 100 pig sera, 82% (n = 82) had detectable antibody against HEV. Of the 200 pig handlers, 28% (56/200) demonstrated jaundice within the past 2 years, whereas only 17% (43/250) of controls had a history of jaundice (p Bangladesh demonstrated evidence of HEV infection, and a history of jaundice was significantly more frequent in pig handlers. Identifying and genotyping HEV in pigs and pig handlers may provide further evidence of the pig's role in zoonotic HEV transmission in Bangladesh. © 2017 Blackwell Verlag GmbH.

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

Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model. The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock-in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined. We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats. We have successfully differentiated

Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based Therapies of Retinal Degenerations.

Science.gov (United States)

Jacobson, Samuel G; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V

2016-04-01

We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.

SoxC transcription factors in retinal development and regeneration

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Kun-Che Chang

2017-01-01

Full Text Available Glaucoma and other optic neuropathies result in optic nerve degeneration and the loss of retinal ganglion cells (RGCs through complex signaling pathways. Although the mechanisms that regulate RGC development remain unclear, uncovering novel developmental pathways may support new strategies to regenerate the optic nerve or replace RGCs. Here we review recent studies that provide strong evidence that the Sry-related high-mobility-group C (SoxC subfamily of transcription factors (TFs are necessary and sufficient for axon guidance and RGC fate specification. These findings also uncover novel SoxC-dependent mechanisms that serve as master regulators during important steps of RGC development. For example, we review work showing that SoxC TFs regulate RGC axon guidance and direction through the optic chiasm towards their appropriate targets in the brain. We also review work demonstrating that Sox11 subcellular localization is, in part, controlled through small ubiquitin-like post-translational modifier (SUMO and suggest compensatory cross-talk between Sox4 and Sox11. Furthermore, Sox4 overexpression is shown to positively drive RGC differentiation in human induced pluripotent stem cells (hiPSCs. Finally, we discuss how these findings may contribute to the advancement of regenerative and cell-based therapies to treat glaucoma and other optic nerve neuropathies.

Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing Acute Visual Disturbance.

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Park, Young Joo; Park, Kyu Hyung; Woo, Se Joon

2017-08-01

To report clinical features of patients with retinal and choroidal diseases presenting with acute visual disturbance during pregnancy. In this retrospective case series, patients who developed acute visual loss during pregnancy (including puerperium) and visited a tertiary hospital from July 2007 to June 2015, were recruited by searching electronic medical records. Patients were categorized according to the cause of visual loss. Clinical features and required diagnostic modalities were analyzed in the retinal and choroidal disease group. Acute visual loss occurred in 147 patients; 49 (38.9%) were classified into the retinal and choroidal group. The diagnoses included central serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre-eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%), diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%), retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%), and others (14.3%). Visual symptoms first appeared at gestational age 25.9 ± 10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 ± 0.39 logarithm of the minimum angle of resolution (logMAR); the final BCVA after delivery improved to 0.13 ± 0.35 logMAR. Serious visual deterioration (BCVA worth than 20 / 200) developed in two patients. Differential diagnoses were established with characteristic fundus and spectral-domain optical coherence tomography findings in all cases. In pregnant women with acute visual loss, retinal and choroidal diseases are common and could be vision threatening. Physicians should be aware of pregnancy-associated retinal and choroidal diseases and their clinical features. The differential diagnosis can be established with non-invasive techniques. © 2017 The Korean Ophthalmological Society

Safety of iPhone retinal photography.

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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.

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.

Impact of swine reproductive technologies on pig and global food production.

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Knox, Robert V

2014-01-01

Reproductive technologies have dramatically changed the way pigs are raised for pork production in developed and developing countries. This has involved such areas as pigs produced/sow, more consistent pig flow to market, pig growth rate and feed efficiency, carcass yield and quality, labor efficiency, and pig health. Some reproductive technologies are in widespread use for commercial pork operations [Riesenbeck, Reprod Domest Anim 46:1-3, 2011] while others are in limited use in specific segments of the industry [Knox, Reprod Domest Anim 46:4-6, 2011]. Significant changes in the efficiency of pork production have occurred as a direct result of the use of reproductive technologies that were intended to improve the transfer of genes important for food production [Gerrits et al., Theriogenology 63:283-299, 2005]. While some technologies focused on the efficiency of gene transfer, others addressed fertility and labor issues. Among livestock species, pig reproductive efficiency appears to have achieved exceptionally high rates of performance (PigCHAMP 2011) [Benchmark 2011, Ames, IA, 12-16]. From the maternal side, this includes pigs born per litter, farrowing rate, as well as litters per sow per year. On the male side, boar fertility, sperm production, and sows served per sire have improved as well [Knox et al., Theriogenology, 70:1202-1208, 2008]. These shifts in the efficiency of swine fertility have resulted in the modern pig as one of the most efficient livestock species for global food production. These reproductive changes have predominantly occurred in developed countries, but data suggests transfer and adoption of these in developing countries as well (FAO STAT 2009; FAS 2006) [World pig meat production: food and agriculture organization of the United Nations, 2009; FAS, 2006) Worldwide Pork Production, 2006]. Technological advancements in swine reproduction have had profound effects on industry structure, production, efficiency, quality, and profitability. In

THE MODULATORY ROLE OF TAURINE IN RETINAL GANGLION CELLS

Science.gov (United States)

Jiang, Zheng; Bulley, Simon; Guzzone, Joseph; Ripps, Harris; Shen, Wen

2017-01-01

Taurine (2-aminoethylsuphonic acid) is present in nearly all animal tissues, and is the most abundant free amino acid in muscle, heart, CNS and retina. Although it is known to be a major cytoprotectant and essential for normal retinal development, its role in retinal neurotransmission and modulation is not well understood. We investigated the response of taurine in retinal ganglion cells, and its effect on synaptic transmission between ganglion cells and their pre-synaptic neurons. We find that taurine-elicited currents in ganglion cells could be fully blocked by both strychnine and SR95531, glycine and GABAA receptor antagonists, respectively. This suggests that taurine-activated receptors might share the antagonists with GABA and glycine receptors. The effect of taurine at micromolar concentrations can effectively suppress spontaneous vesicle release from the pre-synaptic neurons, but had limited effects on light-evoked synaptic signals in ganglion cells. We also describe a metabotropic effect of taurine in the suppression of light-evoked response in ganglion cells. Clearly, taurine acts in multiple ways to modulate synaptic signals in retinal output neurons, ganglion cells. PMID:23392924

[Spontaneous neoplasms in guinea pigs].

Science.gov (United States)

Khar'kovskaia, N A; Khrustalev, S A; Vasil'eva, N N

1977-01-01

The authors present an analysis of the data of foreign literature and the results of their personal studies of spontaneous neoplasms in 40 guinea pigs of national breeding observed during observed during a 5-year period. In 4 of them malignant tumors were diagnosed-lympholeucosis (2 cases), dermoid ovarian cysts and also cancer and adenoma of the adrenal cortex (in one animal). The neoplasms described developed in guinea pigs, aged over 4 years, and they are referred to as mostly common tumors in this species of animals.

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...

Ex vivo electroporation of retinal cells: a novel, high efficiency method for functional studies in primary retinal cultures.

Science.gov (United States)

Vergara, M Natalia; Gutierrez, Christian; O'Brien, David R; Canto-Soler, M Valeria

2013-04-01

Primary retinal cultures constitute valuable tools not only for basic research on retinal cell development and physiology, but also for the identification of factors or drugs that promote cell survival and differentiation. In order to take full advantage of the benefits of this system it is imperative to develop efficient and reliable techniques for the manipulation of gene expression. However, achieving appropriate transfection efficiencies in these cultures has remained challenging. The purpose of this work was to develop and optimize a technique that would allow the transfection of chick retinal cells with high efficiency and reproducibility for multiple applications. We developed an ex vivo electroporation method applied to dissociated retinal cell cultures that offers a significant improvement over other currently available transfection techniques, increasing efficiency by five-fold. In this method, eyes were enucleated, devoid of RPE, and electroporated with GFP-encoding plasmids using custom-made electrodes. Electroporated retinas were then dissociated into single cells and plated in low density conditions, to be analyzed after 4 days of incubation. Parameters such as voltage and number of electric pulses, as well as plasmid concentration and developmental stage of the animal were optimized for efficiency. The characteristics of the cultures were assessed by morphology and immunocytochemistry, and cell viability was determined by ethidium homodimer staining. Cell imaging and counting was performed using an automated high-throughput system. This procedure resulted in transfection efficiencies in the order of 22-25% of cultured cells, encompassing both photoreceptors and non-photoreceptor neurons, and without affecting normal cell survival and differentiation. Finally, the feasibility of the technique for cell-autonomous studies of gene function in a biologically relevant context was tested by carrying out gain and loss-of-function experiments for the

Retrobulbar optic neuritis and rhegmatogenous retinal detachment in a fourteen-year-old girl with retinitis pigmentosa sine pigmento.

Science.gov (United States)

Hatta, M; Hayasaka, S; Kato, T; Kadoi, C

2000-01-01

A 14-year-old girl complained of a sudden decrease in right visual acuity. The patient had night blindness, a mottled retina but no pigments, extinguished scotopic electroretinographic response, central scotoma in the right eye and rhegmatogenous retinal detachment. She had initially received laser photocoagulation around the retinal tear and then corticosteroid therapy, cryoretinopexy and segmental buckling. Her right visual acuity increased to 1.0. The association of retinitis pigmentosa sine pigmento, retrobulbar optic neuritis and rhegmatogenous retinal detachment, as demonstrated in our patient, may be uncommon. Copyright 2000 S. Karger AG, Basel

Pig liver sectorization and segmentation and virtual reality depiction

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Zanchet Dinamar José

2002-01-01

Full Text Available OBJECTIVE: To determine pig liver sectorization and segmentation through the representation of their correlation to portal and hepatic veins, and through the development of virtual reality (VR animation. METHODS: Twenty models were obtained by injection of portal and hepatic veins from Landrace pig livers with a methyl methacrylate solution, and by corrosion of the hepatic parenchyma with chloride acid 35%. VR animation of one of these models was conducted through graphic software (3D Studio Max 3.0. RESULTS: Constant presence of eight segments and six venous drainage sectors was observed. Pig portal vein bifurcation was not noticed. Hepatic veins were named according to their embryological origin. Correlation between venous system and hepatic parenchyma was established by means of VR animation. CONCLUSION: These models facilitated both the study of pig hepatic sectors and segments, and the proposal of hepatic veins nomenclature. These models have also been used for the development of VR animated models which show the correlation between the hepatic parenchyma and the pig liver venous system as well as the observation of them from several points of view.

Automated detection of retinal whitening in malarial retinopathy

Science.gov (United States)

Joshi, V.; Agurto, C.; Barriga, S.; Nemeth, S.; Soliz, P.; MacCormick, I.; Taylor, T.; Lewallen, S.; Harding, S.

2016-03-01

Cerebral malaria (CM) is a severe neurological complication associated with malarial infection. Malaria affects approximately 200 million people worldwide, and claims 600,000 lives annually, 75% of whom are African children under five years of age. Because most of these mortalities are caused by the high incidence of CM misdiagnosis, there is a need for an accurate diagnostic to confirm the presence of CM. The retinal lesions associated with malarial retinopathy (MR) such as retinal whitening, vessel discoloration, and hemorrhages, are highly specific to CM, and their detection can improve the accuracy of CM diagnosis. This paper will focus on development of an automated method for the detection of retinal whitening which is a unique sign of MR that manifests due to retinal ischemia resulting from CM. We propose to detect the whitening region in retinal color images based on multiple color and textural features. First, we preprocess the image using color and textural features of the CMYK and CIE-XYZ color spaces to minimize camera reflex. Next, we utilize color features of the HSL, CMYK, and CIE-XYZ channels, along with the structural features of difference of Gaussians. A watershed segmentation algorithm is used to assign each image region a probability of being inside the whitening, based on extracted features. The algorithm was applied to a dataset of 54 images (40 with whitening and 14 controls) that resulted in an image-based (binary) classification with an AUC of 0.80. This provides 88% sensitivity at a specificity of 65%. For a clinical application that requires a high specificity setting, the algorithm can be tuned to a specificity of 89% at a sensitivity of 82%. This is the first published method for retinal whitening detection and combining it with the detection methods for vessel discoloration and hemorrhages can further improve the detection accuracy for malarial retinopathy.

Tumor necrosis factor and its receptors in the neuroretina and retinal vasculature after ischemia-reperfusion injury in the pig retina

DEFF Research Database (Denmark)

Gesslein, Bodil; Håkansson, Gisela; Gustafsson, Lotta

2010-01-01

Numerous studies have been performed aimed at limiting the extent of retinal injury after ischemia, but there is still no effective pharmacological treatment available. The aim of the present study was to examine the role of tumor necrosis factor (TNF)α and its receptors (TNF-R1 and TNF-R2), espe...

Vitreo-retinal eye surgery robot : sustainable precision

NARCIS (Netherlands)

Meenink, H.C.M.

2011-01-01

Vitreo-retinal eye surgery encompasses the surgical procedures performed on the vitreous humor and the retina. A procedure typically consists of the removal of the vitreous humor, the peeling of a membrane and/or the repair of a retinal detachment. Vitreo-retinal surgery is performed minimal

Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia

DEFF Research Database (Denmark)

Kyhn, Maria Voss; Klassen, Henry; Johansson, Ulrica Englund

2009-01-01

electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.......04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P eyes...... injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically...

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

Science.gov (United States)

Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Astrocytes and Müller cells changes during retinal degeneration in a transgenic rat model of retinitis pigmentosa.

Directory of Open Access Journals (Sweden)

Laura eFernández-Sánchez

2015-12-01

Full Text Available Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer of P23H versus SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

[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.

cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.

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Yijin Tao

Full Text Available The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP. We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs. Form-deprived myopia (FDM was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.

Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

Science.gov (United States)

Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

2014-01-01

Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

Why Danish pig farms have far more land and pigs than Dutch farms?

DEFF Research Database (Denmark)

Willems, Jaap; van Grinsven, H.J.M.; Jacobsen, Brian H

2016-01-01

The Netherlands and Denmark are the two biggest pig meat exporters in Europe, both with a strong focus on the German market. The structure of pig farms is very different: an average Danish pig farm has 3500 pigs, 170 ha of agricultural land on which a major part of the feed cereals are grown...... holdings using external sources of feed supply, and Danish farmers on efficient production of feed cereals on large holdings. Due to a gradual lowering of manure and fertiliser application standards, Dutch farmers increasingly have to process manure and export manure, further increasing the total costs...... pig farmers are less sensitive to nutrient policies and feed prices than those in the Netherlands, but the high debt rate makes the sector vulnerable to low pig prices....

Elucidating the role of AII amacrine cells in glutamatergic retinal waves.

Science.gov (United States)

Firl, Alana; Ke, Jiang-Bin; Zhang, Lei; Fuerst, Peter G; Singer, Joshua H; Feller, Marla B

2015-01-28

Spontaneous retinal activity mediated by glutamatergic neurotransmission-so-called "Stage 3" retinal waves-drives anti-correlated spiking in ON and OFF RGCs during the second week of postnatal development of the mouse. In the mature retina, the activity of a retinal interneuron called the AII amacrine cell is responsible for anti-correlated spiking in ON and OFF α-RGCs. In mature AIIs, membrane hyperpolarization elicits bursting behavior. Here, we postulated that bursting in AIIs underlies the initiation of glutamatergic retinal waves. We tested this hypothesis by using two-photon calcium imaging of spontaneous activity in populations of retinal neurons and by making whole-cell recordings from individual AIIs and α-RGCs in in vitro preparations of mouse retina. We found that AIIs participated in retinal waves, and that their activity was correlated with that of ON α-RGCs and anti-correlated with that of OFF α-RGCs. Though immature AIIs lacked the complement of membrane conductances necessary to generate bursting, pharmacological activation of the M-current, a conductance that modulates bursting in mature AIIs, blocked retinal wave generation. Interestingly, blockade of the pacemaker conductance Ih, a conductance absent in AIIs but present in both ON and OFF cone bipolar cells, caused a dramatic loss of spatial coherence of spontaneous activity. We conclude that during glutamatergic waves, AIIs act to coordinate and propagate activity generated by BCs rather than to initiate spontaneous activity. Copyright © 2015 the authors 0270-6474/15/351675-12$15.00/0.

Reversible bull's-eye maculopathy associated with intravitreal fomivirsen therapy for cytomegalovirus retinitis.

Science.gov (United States)

Stone, T W; Jaffe, G J

2000-08-01

To report two cases in which a bull's eye maculopathy developed after intravitreal injection of fomivirsen. Case reports. A 50-year-old man with acquired immunodeficiency syndrome (AIDS) and refractory cytomegalovirus retinitis developed bull's-eye pigmentary changes in the macula of the right eye after initiating therapy with fomivirsen (Vitravene; CIBA Vision, Atlanta, Georgia) intravitreal injections. These pigmentary changes resolved upon cessation of treatment. A 36-year-old man with AIDS and refractory bilateral cytomegalovirus retinitis developed bull's-eye pigmentary changes in both eyes during bilateral intravitreal treatment with fomivirsen. Vision was not affected. These changes resolved after treatment with fomivirsen was stopped. Fomivirsen, a new medication for the treatment of refractory cytomegalovirus retinitis, may cause a bull's-eye maculopathy in some patients. The bull's-eye maculopathy is reversible and does not appear to affect vision.

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.

Visual Acuity is Related to Parafoveal Retinal Thickness in Patients with Retinitis Pigmentosa and Macular Cysts

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Brockhurst, Robert J.; Gaudio, Alexander R.; Berson, Eliot L.

2008-01-01

Purpose To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. Methods In 316 patients with typical forms of retinitis pigmentosa, we measured visual acuities with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, detected macular cysts with optical coherence tomography (OCT), and quantified retinal thicknesses by OCT. We used the FREQ, LOGISTIC, and GENMOD procedures of SAS to evaluate possible risk factors for cyst prevalence and the MIXED procedure to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. Results We found macular cysts in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (p = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (p = 0.038) and within a ring spanning an eccentricity of 5° to 10° from the foveal center (p = 0.004). Conclusions Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly-inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea. PMID:18552390

Retinal oximetry during treatment of retinal vein occlusion by ranibizumab in patients with high blood pressure and dyslipidemia.

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Keilani, C; Halalchi, A; Wakpi Djeugue, D; Regis, A; Abada, S

2016-12-01

In the present study, we examined retinal vascular oxygen saturation in patients with retinal vein occlusion (RVO), high blood pressure (HBP) and dyslipidemia, before and during intravitreal vascular endothelial growth factor (VEGF) injection (ranibizumab). We retrospectively reviewed the medical records of six patients with visual acuity (VA) reduced by macular edema (ME) secondary to RVO with HBP and dyslipidemia, who underwent intravitreal anti-VEGF injection between October 2014 and February 2015 in the department of ophthalmology of François-Quesnay Hospital at Mantes-la-Jolie (France). The main inclusion criterion was the presence of RVO with ME and decreased VA. The primary endpoint was improvement of retinal venous oxygen saturation in patients with RVO before and 3 months after intravitreal ranibizumab injection. Secondary outcomes were improvement of retinal arterial oxygen saturation, improvement of best-corrected visual acuity (BCVA) on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, regression of ME measured by the central macular thickness (CMT) in nm and studying the correlation between blood pressure (BP) and retinal venous oxygen saturation before and after ranibizumab. Six eyes of six patients were included. Before treatment, the mean (standard deviation [SD]) of the retinal venous saturation (%) was 38.1±14.2. Three months after the injections, the mean (SD) of the retinal venous saturation (%) increased statistically significantly 49.2±11 (P=0.03). In this study, retinal venous oxygen saturation in patients with RVO, HBP and dyslipidemia was partially normalized during intravitreal ranibizumab treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Swine dysentery: protection of pigs by oral and parenteral immunisation with attenuated Treponema hyodysenteriae.

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Hudson, M J; Alexander, T J; Lysons, R J; Prescott, J F

1976-11-01

An attenuated strain of Treponema hyodysenteriae was used to immunise 18 pigs in three experiments. Live attenuated spirochaetes were dosed orally and injected intra-peritoneally, and killed spirochaetes were injected intramuscularly with adjuvant. The vaccinated pigs, which developed high serum agglutination titres against T hyodysenteriae, and 18 unvaccinated litter-mates were repeatedly challenged with virulent T hyodysenteriae. Nine vaccinated pigs and 16 control pigs developed typical swine dysentery.

Risk of serous retinal detachment in patients with end-stage renal disease on dialysis.

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Yuh-Shin Chang

Full Text Available The aim of this retrospective, nationwide, matched cohort study was to investigate the association of serous retinal detachment with having end-stage renal disease (ESRD while on dialysis. The cohort study included 94,024 patients with ESRD on dialysis registered between January 2000 to December 2009 in the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 94,024 patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. Twenty-seven ESRD patients and 11 controls developed serous retinal detachment (P < 0.001 during follow-up, demonstrating a significantly increased risk of serous retinal detachment in patients with ESRD on dialysis compared with controls (incidence rate ratio = 3.39, 95% confidence interval [CI] = 1.68-6.83. After adjustment for potential confounders, patients were 3.86 times more likely to develop serous retinal detachment than the full cohort (adjusted HR = 3.86, 95% CI = 1.15-12.96. In conclusion, patients with ESRD on dialysis demonstrate an increased risk of serous retinal detachment. Interdisciplinary collaboration between nephrologists and ophthalmologists is important to deal with serous retinal detachment in patients with ESRD on dialysis and prevent impairments of visual acuity.

A method for volumetric retinal tissue oxygen tension imaging.

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Felder, Anthony E; Wanek, Justin; Teng, Pang-Yu; Blair, Norman P; Shahidi, Mahnaz

2018-01-01

Inadequate retinal oxygenation occurs in many vision-threatening retinal diseases, including diabetic retinopathy, retinal vascular occlusions, and age-related macular degeneration. Therefore, techniques that assess retinal oxygenation are necessary to understand retinal physiology in health and disease. The purpose of the current study is to report a method for the three-dimensional (3D) imaging of retinal tissue oxygen tension (tPO 2 ) in rats. Imaging was performed in Long Evans pigmented rats under systemic normoxia (N = 6) or hypoxia (N = 3). A vertical laser line was horizontally scanned on the retina and a series of optical section phase-delayed phosphorescence images were acquired. From these images, phosphorescence volumes at each phase delay were constructed and a 3D retinal tPO 2 volume was generated. Retinal tPO 2 volumes were quantitatively analyzed by generating retinal depth profiles of mean tPO 2 (M tPO2 ) and the spatial variation of tPO 2 (SV tPO2 ). The effects of systemic condition (normoxia/hypoxia) and retinal depth on M tPO2 and SV tPO2 were determined by mixed linear model. Each 3D retinal tPO 2 volume was approximately 500 × 750 × 200 μm (horizontal × vertical × depth) and consisted of 45 en face tPO 2 images through the retinal depth. M tPO2 at the chorioretinal interface was significantly correlated with systemic arterial oxygen tension (P = 0.007; N = 9). There were significant effects of both systemic condition and retinal depth on M tPO2 and SV tPO2 , such that both were lower under hypoxia than normoxia and higher in the outer retina than inner retina (P < 0.001). For the first time, 3D imaging of retinal tPO 2 was demonstrated, with potential future application for assessment of physiological alterations in animal models of retinal diseases.

The surface morphology of retinal breaks and lattice retinal degeneration. A scanning electron microscopic study.

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Robinson, M R; Streeten, B W

1986-02-01

In 14 of 110 eye bank eyes, lesions characteristic of peripheral retinal surface pathology were examined by scanning electron microscopy (SEM). These included operculated and flap tears, trophic round holes, lattice degeneration with holes, and paravascular retinal "pitting" degeneration. By SEM, the edges of the retinal breaks were covered by smooth cellular membranes, merging peripherally with a meshwork of vitreous fibrils. The membrane cells had poorly defined borders, a pitted surface, and variable numbers of microvilli consistent with glia. Lattice surfaces and foci of paravascular retinal degeneration were covered by similar membrane, but showed characteristic differences. It appears that breaks in the internal limiting membrane always stimulate proliferation of preretinal glial membranes. Similar cellular morphology of the membranes associated with breaks is consistent with a common cell of origin. Limited proliferation of these membranes suggests that surface gliosis is normally inhibited when the cells contact either intact basement membrane or vitreous.

Retinal glia promote dorsal root ganglion axon regeneration.

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Barbara Lorber

Full Text Available Axon regeneration in the adult central nervous system (CNS is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.

Application of morphological bit planes in retinal blood vessel extraction.

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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.

Toward high-resolution optoelectronic retinal prosthesis

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Palanker, Daniel; Huie, Philip; Vankov, Alexander; Asher, Alon; Baccus, Steven

2005-04-01

It has been already demonstrated that electrical stimulation of retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. Current retinal implants provide very low resolution (just a few electrodes), while several thousand pixels are required for functional restoration of sight. We present a design of the optoelectronic retinal prosthetic system that can activate a retinal stimulating array with pixel density up to 2,500 pix/mm2 (geometrically corresponding to a visual acuity of 20/80), and allows for natural eye scanning rather than scanning with a head-mounted camera. The system operates similarly to "virtual reality" imaging devices used in military and medical applications. An image from a video camera is projected by a goggle-mounted infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. Such a system provides a broad field of vision by allowing for natural eye scanning. The goggles are transparent to visible light, thus allowing for simultaneous utilization of remaining natural vision along with prosthetic stimulation. Optical control of the implant allows for simple adjustment of image processing algorithms and for learning. A major prerequisite for high resolution stimulation is the proximity of neural cells to the stimulation sites. This can be achieved with sub-retinal implants constructed in a manner that directs migration of retinal cells to target areas. Two basic implant geometries are described: perforated membranes and protruding electrode arrays. Possibility of the tactile neural stimulation is also examined.

Real-Time Imaging of Retinal Ganglion Cell Apoptosis

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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.

The effect of trichlorfon and methylazoxymethanol on the development of guinea pig cerebellum

International Nuclear Information System (INIS)

Mehl, Anna; Schanke, Tore M.; Torvik, Ansgar; Fonnum, Frode

2007-01-01

The pesticide trichlorfon (125 mg/kg on days 42-44 in gestation) gives hypoplasia of Brain of the offspring without any significant reduction in their body weights. The hypoplasia may be caused by trichlorfon itself or by its metabolite dichlorvos. This period of development coincides with the growth spurt period of guinea pig brain. The largest changes occurred in the cerebellum. Electron microscopic examination of the cerebellar cortex showed increased apoptotic death of cells in the granule cell layer after trichlorfon treatment. A reduction in thickness of the external germinal layer of the cerebellar cortex and an elevated amount of pyknotic and karyorrhexic cells in the granule cell layer was found. There was a significant reduction in choline esterase, choline acetyltransferase and glutamate decarboxylase activities in the cerebellum. Methylazoxymethanol (15 mg/kg body weight, day 43) was examined for comparison and caused similar hypoplasia of the guinea pig cerebellum, but did also induce a reduction in body weight. Trichloroethanol, the main metabolite of trichlorfon, did not give brain hypoplasia

Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment

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L. Sh. Bilandarli

2017-01-01

Full Text Available Review describes the theme of rhegmatogenous retinal dеtаchment associated with choroidal separation. It is rare, but quite severe eye pathology. In most cases it has a very poor prognosis. Most authors consider the retinal detachment as a primary pathogenetic part, which decompensates the production of aqueous humor by increasing the absorptive surface of the retinal pigment epithelium. Dilatation of choroidal arterioles occurs in hypotension, it leads to extravasation of protein-rich fluid in the choroidal and the suprachoroidal space. This helps to further swelling and separation of the ciliary body and the choroid with reduced production of aqueous humor and progressive hypotension. There is a high risk of developing “retino-choroidal” separation in patients with macular rupture due to localization of retinal separation and rupture rear hyaloid membrane. The protein level in aqueous humor can be increased to 70 times. It may be a result of reflux of suprachoroidal proteins through uveoscleral route and / or venous proteins through the trabecular network. In addition, the diffusion of proteins from the posterior camera and vitreous cavity is possible. This creates favorable conditions for cell proliferation that can lead to postoperative proliferative vitreoretinopathy. Typically patients have a pronounced signs of inflammation, pain, and “red eye”, which is accompanied with vision decrement. Rhegmatogenous retinal reparationcan be associated with such clinical symptoms as severe panuveit, deepening of the anterior camera and the inflammatory response in the moisture, concentric wrinkles and sagging back of the iris, posterior synechia, iridofakodenez, blurred vitreous detachment of the ciliary body, hypotension, and choroidal and retinal detachment in addition. Debatableness of etiopathogenesis and a clinical picture, which is similar to other eye diseases create significant difficulties in early diagnosis and proper treatment of

Spatial analysis and characteristics of pig farming in Thailand.

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Thanapongtharm, Weerapong; Linard, Catherine; Chinson, Pornpiroon; Kasemsuwan, Suwicha; Visser, Marjolein; Gaughan, Andrea E; Epprech, Michael; Robinson, Timothy P; Gilbert, Marius

2016-10-06

In Thailand, pig production intensified significantly during the last decade, with many economic, epidemiological and environmental implications. Strategies toward more sustainable future developments are currently investigated, and these could be informed by a detailed assessment of the main trends in the pig sector, and on how different production systems are geographically distributed. This study had two main objectives. First, we aimed to describe the main trends and geographic patterns of pig production systems in Thailand in terms of pig type (native, breeding, and fattening pigs), farm scales (smallholder and large-scale farming systems) and type of farming systems (farrow-to-finish, nursery, and finishing systems) based on a very detailed 2010 census. Second, we aimed to study the statistical spatial association between these different types of pig farming distribution and a set of spatial variables describing access to feed and markets. Over the last decades, pig population gradually increased, with a continuously increasing number of pigs per holder, suggesting a continuing intensification of the sector. The different pig-production systems showed very contrasted geographical distributions. The spatial distribution of large-scale pig farms corresponds with that of commercial pig breeds, and spatial analysis conducted using Random Forest distribution models indicated that these were concentrated in lowland urban or peri-urban areas, close to means of transportation, facilitating supply to major markets such as provincial capitals and the Bangkok Metropolitan region. Conversely the smallholders were distributed throughout the country, with higher densities located in highland, remote, and rural areas, where they supply local rural markets. A limitation of the study was that pig farming systems were defined from the number of animals per farm, resulting in their possible misclassification, but this should have a limited impact on the main patterns revealed

Animal models got you puzzled?: think pig.

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Walters, Eric M; Agca, Yuksel; Ganjam, Venkataseshu; Evans, Tim

2011-12-01

Swine are an excellent large animal model for human health and disease because their size and physiology are similar to humans, in particular, with respect to the skin, heart, gastrointestinal tract, and kidneys. In addition, the pig has many emerging technologies that will only enhance the development of the pig as the nonrodent biomedical model of choice. © 2011 New York Academy of Sciences.

A Method for Combined Retinal Vascular and Tissue Oxygen Tension Imaging.

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

2017-09-06

The retina requires adequate oxygenation to maintain cellular metabolism and visual function. Inner retinal oxygen metabolism is directly related to retinal vascular oxygen tension (PO 2 ) and inner retinal oxygen extraction fraction (OEF), whereas outer retinal oxygen consumption (QO 2 ) relies on oxygen availability by the choroid and is contingent upon retinal tissue oxygen tension (tPO 2 ) gradients across the retinal depth. Thus far, these oxygenation and metabolic parameters have been measured independently by different techniques in separate animals, precluding a comprehensive and correlative assessment of retinal oxygenation and metabolism dynamics. The purpose of the current study is to report an innovative optical system for dual oxyphor phosphorescence lifetime imaging to near-simultaneously measure retinal vascular PO 2 and tPO 2 in rats. The use of a new oxyphor with different spectral characteristics allowed differentiation of phosphorescence signals from the retinal vasculature and tissue. Concurrent measurements of retinal arterial and venous PO 2 , tPO 2 through the retinal depth, inner retinal OEF, and outer retinal QO 2 were demonstrated, permitting a correlative assessment of retinal oxygenation and metabolism. Future application of this method can be used to investigate the relations among retinal oxygen content, extraction and metabolism under pathologic conditions and thus advance knowledge of retinal hypoxia pathophysiology.

Retinal layer measurements after successful macula-off retinal detachment repair using optical coherence tomography.

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Menke, Marcel N; Kowal, Jens H; Dufour, Pascal; Wolf-Schnurrbusch, Ute E; Ceklic, Lala; Framme, Carsten; Wolf, Sebastian

2014-09-04

Optical coherence tomography (OCT) was used to analyze the thickness of various retinal layers of patients following successful macula-off retinal detachment (RD) repair. Optical coherence tomography scans of patients after successful macula-off RD repair were reanalyzed with a subsegmentation algorithm to measure various retinal layers. Regression analysis was performed to correlate time after surgery with changes in layer thickness. In addition, patients were divided in two groups. Group 1 had a follow-up period after surgery of up to 7 weeks (range, 21-49 days). In group 2, the follow-up period was >8 weeks (range, 60-438 days). Findings were compared to a group of age-matched healthy controls. Correlation analysis showed a significant positive correlation between inner nuclear-outer plexiform layer (INL-OPL) thickness and time after surgery (P=0.0212; r2=0.1551). Similar results were found for the ellipsoid zone-retinal pigment epithelium complex (EZ-RPE) thickness (P=0.005; r2=0.2215). Ganglion cell-inner plexiform layer thickness (GCL-IPL) was negatively correlated with time after surgery (P=0.0064; r2=0.2101). For group comparison, the retinal nerve fiber layer in both groups was thicker compared to controls. The GCL-IPL showed significant thinning in group 2. The outer nuclear layer was significantly thinner in groups 1 and 2 compared to controls. The EZ-RPE complex was significantly thinner in groups 1 and 2 compared to controls. In addition, values in group 1 were significantly thinner than in group 2. Optical coherence tomography retinal layer thickness measurements after successful macular-off RD repair revealed time-dependent thickness changes. Inner nuclear-outer plexiform layer thickness and EZ-RPE thickness was positively correlated with time after surgery. Ganglion cell-inner plexiform layer thickness was negatively correlated with time after surgery. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Gene Correction Reverses Ciliopathy and Photoreceptor Loss in iPSC-Derived Retinal Organoids from Retinitis Pigmentosa Patients

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Wen-Li Deng

2018-04-01

Full Text Available Summary: Retinitis pigmentosa (RP is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity. Furthermore, shorted cilium was found in patient iPSCs, RPE cells, and three-dimensional retinal organoids. CRISPR-Cas9-mediated correction of RPGR mutation rescued photoreceptor structure and electrophysiological property, reversed the observed ciliopathy, and restored gene expression to a level in accordance with that in the control using transcriptome-based analysis. This study recapitulated the pathogenesis of RPGR using patient-specific organoids and achieved targeted gene therapy of RPGR mutations in a dish as proof-of-concept evidence. : Jin and colleagues demonstrate that patient-specific iPSC-derived 3D retinae can recapitulate disease progress of retinitis pigmentosa through presenting defects in photoreceptor morphology, gene profile, and electrophysiology, as well as the defective ciliogenesis in iPSCs, iPSC-RPE, and 3D retinae. CRISPR/Cas9-mediated gene correction can rescue not only photoreceptor structure and electrophysiological property but also observed ciliopathy. Keywords: RPGR, photoreceptor, electrophysiology, retinitis pigmentosa, patient-derived iPSCs, retinal organoid, RPE cells, cilium, ciliopathy, disease modeling

A Probabilistic Framework for Content-Based Diagnosis of Retinal Disease

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

2007-01-01

Diabetic retinopathy is the leading cause of blindness in the working age population around the world. Computer assisted analysis has the potential to assist in the early detection of diabetes by regular screening of large populations. The widespread availability of digital fundus cameras today is resulting in the accumulation of large image archives of diagnosed patient data that captures historical knowledge of retinal pathology. Through this research we are developing a content-based image retrieval method to verify our hypothesis that retinal pathology can be identified and quantified from visually similar retinal images in an image archive. We will present diagnostic results for specificity and sensitivity on a population of 395 fundus images representing the normal fundus and 14 stratified disease states.

A clinical approach to the diagnosis of retinal vasculitis.

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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.

MR detection of retinal hemorrhages: correlation with graded ophthalmologic exam

International Nuclear Information System (INIS)

Beavers, Angela J.; Allbery, Sandra M.; Stagner, Anna M.; Hejkal, Thomas W.; Lyden, Elizabeth R.; Haney, Suzanne B.

2015-01-01

Dilated fundoscopic exam is considered the gold standard for detecting retinal hemorrhage, but expertise in obtaining this exam is not always immediately available. MRI can detect retinal hemorrhages, but correlation of the grade or severity of retinal hemorrhage on dilated fundoscopic exam with retinal hemorrhage visibility on MRI has not been described. To determine the value of standard brain protocol MRI in detecting retinal hemorrhage and to determine whether there is any correlation with MR detection of retinal hemorrhage and the dilated fundoscopic exam grade of hemorrhage. We conducted a retrospective chart review of 77 children <2 years old who were seen for head trauma from April 2007 to July 2013 and had both brain MRI and dilated fundoscopic exam or retinal camera images. A staff pediatric radiologist and radiology resident reviewed the MR images. Retinal hemorrhages were graded by a chief ophthalmology resident on a 12-point scale based on the retinal hemorrhage type, size, location and extent as seen on review of retinal camera images and detailed reports by ophthalmologists. Higher scores indicated increased severity of retinal hemorrhages. There was a statistically significant difference in the median grade of retinal hemorrhage examination between children who had retinal hemorrhage detected on MRI and children who did not have retinal hemorrhage detected on MRI (P = 0.02). When examination grade was categorized as low-grade (1-4), moderate-grade (5-8) or high-grade (>8) hemorrhage, there was a statistically significant association between exam grade and diagnosis based on MRI (P = 0.008). For example, only 14% of children with low-grade retinal hemorrhages were identified on MRI compared to 76% of children with high-grade hemorrhages. MR detection of retinal hemorrhage demonstrated a sensitivity of 61%, specificity of 100%, positive predictive value of 100% and negative predictive value of 63%. Retinal hemorrhage was best seen on the gradient

Effects of Increasing Space Allowance by Removing a Pig or Gate Adjustment on Finishing Pig Growth Performance.

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Carpenter, Corey B; Holder, Cheyenne J; Wu, Fanghou; Woodworth, Jason C; DeRouchey, Joel M; Tokach, Mike D; Goodband, Robert D; Dritz, Steve S

2018-05-03

A total of 256 pigs (initially 55.9 ± 4.88 kg) were used in a 71-d study to determine the effects of increasing space allowance and pig removal on pig growth performance. Pens of pigs were blocked by body weight (BW) and allotted to one of four space allowance treatments, initially with 8 pigs per pen and 8 pens per treatment. First two treatments included pens with 0.91 m2 per pig or 0.63 m2 per pig for the entire study; two additional treatments initially provided 0.63 m2 per pig, but either a gate was adjusted on d 28, 45, and 62 or the heaviest pig in the pen was removed from the pen on d 28 and 45 to provide more space and keep pigs in accordance with their predicted minimum space requirement [(m2) = 0.0336 × (BW, kg)0.67]. From d 0 to 14 (56 to 69 kg), there was no effect of stocking density observed for average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F). From d 14 to 28 (69 to 83 kg), pigs provided 0.91 m2 had increased (P space adjustment treatments had greater (P space adjustments intermediate. In summary, pigs with 0.91 m2 grew faster and consumed more feed than pigs restricted in space. As pigs reached the critical k value, gate adjustments and pig removals affected growth similarly. As pigs grew to the predicted space requirement and were subsequently allowed more space, performance was greater than those provided 0.63 m2 but less than those allowed 0.91 m2. It appears that the industry accepted critical k value, 0.0336, may not be adequate for optimal pig performance across multiple BW ranges.

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

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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.

ECG telemetry in conscious guinea pigs.

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Ruppert, Sabine; Vormberge, Thomas; Igl, Bernd-Wolfgang; Hoffmann, Michael

2016-01-01

During preclinical drug development, monitoring of the electrocardiogram (ECG) is an important part of cardiac safety assessment. To detect potential pro-arrhythmic liabilities of a drug candidate and for internal decision-making during early stage drug development an in vivo model in small animals with translatability to human cardiac function is required. Over the last years, modifications/improvements regarding animal housing, ECG electrode placement, and data evaluation have been introduced into an established model for ECG recordings using telemetry in conscious, freely moving guinea pigs. Pharmacological validation using selected reference compounds affecting different mechanisms relevant for cardiac electrophysiology (quinidine, flecainide, atenolol, dl-sotalol, dofetilide, nifedipine, moxifloxacin) was conducted and findings were compared with results obtained in telemetered Beagle dogs. Under standardized conditions, reliable ECG data with low variability allowing largely automated evaluation were obtained from the telemetered guinea pig model. The model is sensitive to compounds blocking cardiac sodium channels, hERG K(+) channels and calcium channels, and appears to be even more sensitive to β-blockers as observed in dogs at rest. QT interval correction according to Bazett and Sarma appears to be appropriate methods in conscious guinea pigs. Overall, the telemetered guinea pig is a suitable model for the conduct of early stage preclinical ECG assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

Science.gov (United States)

Lambertus, Stanley; Bax, Nathalie M; Fakin, Ana; Groenewoud, Joannes M M; Klevering, B Jeroen; Moore, Anthony T; Michaelides, Michel; Webster, Andrew R; van der Wilt, Gert Jan; Hoyng, Carel B

2017-01-01

Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in

Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

Directory of Open Access Journals (Sweden)

Stanley Lambertus

Full Text Available Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration.We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14 and the United Kingdom (external validation cohort, n = 18. The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52. Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904. These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872. We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients.These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease

Trends in slaughter pig production and antimicrobial consumption in Danish slaughter pig herds, 2002-2008

DEFF Research Database (Denmark)

Vieira, Antonio; Pires, Sara Monteiro; Houe, H.

2011-01-01

Overuse of antimicrobials in food-animal production is thought to be a major risk factor for the development of resistant bacterial populations. Data on non-human antimicrobial usage is essential for planning of intervention strategies to lower resistance levels at the country, region or herd...... levels. In this study we evaluated Danish national antimicrobial usage data for five antimicrobial classes used in slaughter pigs in different herd sizes and data on the number of slaughter pigs produced per herd, between 2002 and 2008, in Denmark. The objective was to ascertain...... if there is an association between herd size and amount of antimicrobials consumed. During this period, the overall number of herds with slaughter pigs decreased by 43%, with larger herds becoming more prevalent. The tetracycline treatment incidence (TI) rate increased from 0·28 to 0·70 animal-defined daily dose (ADD)/100...

Wireless technologies for closed-loop retinal prostheses

Science.gov (United States)

Ng, David C.; Bai, Shun; Yang, Jiawei; Tran, Nhan; Skafidas, Efstratios

2009-12-01

In this paper, we discuss various technologies needed to develop retinal prostheses with wireless power and data telemetry operation. In addition to the need to communicate with the implanted device, supply of power to the retinal prosthesis is especially difficult. This is because, in the implanted state, the device is not fixed in position due to constant motion of the eye. Furthermore, a retinal prosthesis incorporating a high density electrode array of more than 1000 electrodes is expected to consume approximately 45 mW of power and require 300 kbps of image and stimulation data. The front end of the wireless power and data transmission, the antenna, needs to be small compared to the size of the eye. Also, the wireless module is expected to operate in the reactive near-field region due to small separation between the transmit and receive antennas compared to their size and corresponding operating wavelength. An inductive link is studied as a means to transfer power and for data telemetry between the implant and external unit. In this work, the use of integrated circuit and microfabrication technologies for implementing inductive links is discussed. A closed-loop approach is taken to improve performance and reach optimum operation condition. Design and simulation data are presented as the basis for development of viable wireless module prototypes.

Drusen-like beneath retinal deposits in type II mesangiocapillary glomerulonephritis: a review

Directory of Open Access Journals (Sweden)

Miguel Hage Amaro

2015-02-01

Full Text Available The aim of this paper is to do a review of Drusen-like beneath retinal deposits in type II mesangiocapillary glomerulonephritis. Drusenlike beneath retinal deposits in type II mesangiocapillary glomerulonephritis appear to develop at an early age, often second decade of life different of drusen from age-related macular degeneration (AMD.Long term follow-up of the cases in this disease shows in the most of them, no progression of the of drusen-like beneath retinal deposits in type II mesangiocapillary glomerulonefritis, the most of subjects retain good visual acuity and no specific treatment is indicated.

Novel Strategies for the Improvement of Stem Cells' Transplantation in Degenerative Retinal Diseases

Science.gov (United States)

Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga

2016-01-01

Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation. PMID:27293444

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.

Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population.

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Maeda, Akiko; Yoshida, Akiko; Kawai, Kanako; Arai, Yuki; Akiba, Ryutaro; Inaba, Akira; Takagi, Seiji; Fujiki, Ryoji; Hirami, Yasuhiko; Kurimoto, Yasuo; Ohara, Osamu; Takahashi, Masayo

2018-05-21

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. Evaluation of diagnostic technology, Prospective, Clinical and experimental study. A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.

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.

Retinal oxygen saturation before and after glaucoma surgery.

Science.gov (United States)

Nitta, Eri; Hirooka, Kazuyuki; Shimazaki, Takeru; Sato, Shino; Ukegawa, Kaori; Nakano, Yuki; Tsujikawa, Akitaka

2017-08-01

This study compared retinal vessel oxygen saturation before and after glaucoma surgery. Retinal oxygen saturation in glaucoma patients was measured using a non-invasive spectrophotometric retinal oximeter. Adequate image quality was found in 49 of the 108 consecutive glaucoma patients recruited, with 30 undergoing trabeculectomy, 11 EX-PRESS and eight trabeculotomy. Retinal oxygen saturation measurements in the retinal arterioles and venules were performed at 1 day prior to and at approximately 10 days after surgery. Statistical analysis was performed using a Student's t-test. After glaucoma surgery, intraocular pressure (IOP) decreased from 19.8 ± 7.7 mmHg to 9.0 ± 5.7 mmHg (p glaucoma surgery had an effect on the retinal venous oxygen saturation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[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.

Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)

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Hara, Hideaki

2017-01-01

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress. PMID:28194256

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.

Semi-automated retinal vessel analysis in nonmydriatic fundus photography.

Science.gov (United States)

Schuster, Alexander Karl-Georg; Fischer, Joachim Ernst; Vossmerbaeumer, Urs

2014-02-01

Funduscopic assessment of the retinal vessels may be used to assess the health status of microcirculation and as a component in the evaluation of cardiovascular risk factors. Typically, the evaluation is restricted to morphological appreciation without strict quantification. Our purpose was to develop and validate a software tool for semi-automated quantitative analysis of retinal vasculature in nonmydriatic fundus photography. matlab software was used to develop a semi-automated image recognition and analysis tool for the determination of the arterial-venous (A/V) ratio in the central vessel equivalent on 45° digital fundus photographs. Validity and reproducibility of the results were ascertained using nonmydriatic photographs of 50 eyes from 25 subjects recorded from a 3DOCT device (Topcon Corp.). Two hundred and thirty-three eyes of 121 healthy subjects were evaluated to define normative values. A software tool was developed using image thresholds for vessel recognition and vessel width calculation in a semi-automated three-step procedure: vessel recognition on the photograph and artery/vein designation, width measurement and calculation of central retinal vessel equivalents. Mean vessel recognition rate was 78%, vessel class designation rate 75% and reproducibility between 0.78 and 0.91. Mean A/V ratio was 0.84. Application on a healthy norm cohort showed high congruence with prior published manual methods. Processing time per image was one minute. Quantitative geometrical assessment of the retinal vasculature may be performed in a semi-automated manner using dedicated software tools. Yielding reproducible numerical data within a short time leap, this may contribute additional value to mere morphological estimates in the clinical evaluation of fundus photographs. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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. ...

Retinal vascular and structural dynamics during acute hyperglycaemia

DEFF Research Database (Denmark)

Klefter, Oliver N; Lauritsen, Tina Vilsbøll; Knop, Filip K

2015-01-01

PURPOSE: To compare retinal vascular dynamics during acute hyperglycaemia in patients with type 2 diabetes and healthy volunteers. METHODS: Twenty-one patients with type 2 diabetes and 27 healthy controls were examined with fundus photographic measurement of retinal vessel diameters, retinal...

Calibration and validation of a physiologically based model for soman intoxication in the rat, marmoset, guinea pig and pig.

Science.gov (United States)

Chen, Kaizhen; Seng, Kok-Yong

2012-09-01

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model has been developed for low, medium and high levels of soman intoxication in the rat, marmoset, guinea pig and pig. The primary objective of this model was to describe the pharmacokinetics of soman after intravenous, intramuscular and subcutaneous administration in the rat, marmoset, guinea pig, and pig as well as its subsequent pharmacodynamic effects on blood acetylcholinesterase (AChE) levels, relating dosimetry to physiological response. The reactions modelled in each physiologically realistic compartment are: (1) partitioning of C(±)P(±) soman from the blood into the tissue; (2) inhibition of AChE and carboxylesterase (CaE) by soman; (3) elimination of soman by enzymatic hydrolysis; (4) de novo synthesis and degradation of AChE and CaE; and (5) aging of AChE-soman and CaE-soman complexes. The model was first calibrated for the rat, then extrapolated for validation in the marmoset, guinea pig and pig. Adequate fits to experimental data on the time course of soman pharmacokinetics and AChE inhibition were achieved in the mammalian models. In conclusion, the present model adequately predicts the dose-response relationship resulting from soman intoxication and can potentially be applied to predict soman pharmacokinetics and pharmacodynamics in other species, including human. Copyright © 2011 John Wiley & Sons, Ltd.

Spatial-temporal patterns of retinal waves underlying activity-dependent refinement of retinofugal projections.

Science.gov (United States)

Stafford, Ben K; Sher, Alexander; Litke, Alan M; Feldheim, David A

2009-10-29

During development, retinal axons project coarsely within their visual targets before refining to form organized synaptic connections. Spontaneous retinal activity, in the form of acetylcholine-driven retinal waves, is proposed to be necessary for establishing these projection patterns. In particular, both axonal terminations of retinal ganglion cells (RGCs) and the size of receptive fields of target neurons are larger in mice that lack the beta2 subunit of the nicotinic acetylcholine receptor (beta2KO). Here, using a large-scale, high-density multielectrode array to record activity from hundreds of RGCs simultaneously, we present analysis of early postnatal retinal activity from both wild-type (WT) and beta2KO retinas. We find that beta2KO retinas have correlated patterns of activity, but many aspects of these patterns differ from those of WT retina. Quantitative analysis suggests that wave directionality, coupled with short-range correlated bursting patterns of RGCs, work together to refine retinofugal projections.

Varicella Zoster Virus Necrotizing Retinitis in Two Patients with Idiopathic CD4 Lymphocytopenia.

Science.gov (United States)

Gupta, Meenakashi; Jardeleza, Maria Stephanie R; Kim, Ivana; Durand, Marlene L; Kim, Leo; Lobo, Ann-Marie

2016-10-01

Progressive outer retinal necrosis (PORN) associated with varicella zoster virus (VZV) is usually diagnosed in HIV positive or immunosuppressed patients. We report two cases of immunocompetent patients with necrotizing viral retinitis found to have idiopathic CD4 lymphocytopenia. Clinical presentation, examination, imaging, and laboratory testing of two patients with VZV retinitis are presented. An HIV negative patient with history of herpes zoster presented with rapid loss of vision and examination consistent with PORN. PCR testing confirmed VZV. Lymphocytopenia was noted with a CD4 count of 25/mm(3). A second HIV negative patient presented with blurred vision and lid swelling and was found to have peripheral VZV retinitis confirmed by PCR. Laboratory workup revealed lymphocytopenia with a CD4 count of 133/mm(3). VZV necrotizing retinitis classic for PORN can occur in HIV negative patients. Idiopathic CD4 lymphocytopenia should be considered healthy patients who develop ocular infections seen in the immunocompromised.

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.

Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration.

Science.gov (United States)

Zhang, Qian; Zhang, Zuo-Ming

2014-04-25

It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (Poxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

Adaptive Optics Technology for High-Resolution Retinal Imaging

Science.gov (United States)

Lombardo, Marco; Serrao, Sebastiano; Devaney, Nicholas; Parravano, Mariacristina; Lombardo, Giuseppe

2013-01-01

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging. PMID:23271600

Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

Science.gov (United States)

Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

2016-10-01

Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Study and development of retinal dopamine nervous system in experimental myopia

International Nuclear Information System (INIS)

Zhao Juan; Liu Xingdang

2007-01-01

Myopia is the most familiar ametropia. Animal experimental models include form deprivation myopia and defocus myopia. Experimental animals we often use are chicken and mammals. The retinal dopamine system and vision experience have close relations with the regulation of eyeball's growth after birth, while the change of dopamine transporter may reflect the change of dopamine in the synaptic cleft more directly. (authors)

[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.

Assessing pig body language: agreement and consistency between pig farmers, veterinarians, and animal activists.

Science.gov (United States)

Wemelsfelder, F; Hunter, A E; Paul, E S; Lawrence, A B

2012-10-01

This study investigates the interobserver and intraobserver reliability of qualitative behavior assessments (QBA) of individual pigs by 3 observer groups selected for their diverging backgrounds, experience, and views of pigs. Qualitative behavior assessment is a "whole animal" assessment approach that characterizes the demeanor of an animal as an expressive body language, using descriptors such as relaxed, anxious, or content. This paper addresses the concern that use of such descriptors in animal science may be prone to distortion by observer-related bias. Using a free-choice profiling methodology, 12 pig farmers, 10 large animal veterinarians, and 10 animal protectionists were instructed to describe and score the behavioral expressions of 10 individual pigs (sus scrofa) in 2 repeat sets of 10 video clips, showing these pigs in interaction with a human female. They were also asked to fill in a questionnaire gauging their experiences with and views on pigs. Pig scores were analyzed with generalized procrustes analysis and effect of treatment on these scores with ANOVA. Questionnaire scores were analyzed with a χ(2) test or ANOVA. Observers achieved consensus both within and among observer groups (P 0.90). The 3 groups also repeated their assessments of individual pigs with high precision (r > 0.85). Animal protectionists used a wider quantitative range in scoring individual pigs on dimension 2 than the other groups (P body language. This supports the empirical nature of QBA in context of the wider anthropomorphism debate.

Regulation of retinal proteome by topical antiglaucomatous eye drops in an inherited glaucoma rat model.

Directory of Open Access Journals (Sweden)

Maurice Schallenberg

Full Text Available Examination of the response of the retinal proteome to elevated intraocular pressure (IOP and to the pharmacological normalization of IOP is crucial, in order to develop drugs with neuroptorective potential. We used a hereditary rat model of ocular hypertension to lower IOP with travaprost and dorzolamide applied topically on the eye surface, and examine changes of the retinal proteome. Our data demonstrate that elevated IOP causes alterations in the retinal protein profile, in particular in high-mobility-group-protein B1 (HMGB1, calmodulin, heat-shock-protein (HSP 70 and carbonic anhydrase II expression. The changes of the retinal proteome by dorzolamide or travoprost are different and independent of the IOP lowering effect. This fact suggests that the eye drops exert a direct IOP-independent effect on retinal metabolism. Further investigations are required to elucidate the potential neuroprotective mechanisms signaled through changes of HMGB1, calmodulin, HSP70 and carbonic anhydrase II expression in glaucoma. The data may facilitate development of eye drops that exert neuroprotection through direct pharmacological effect.

Rapid glutamate receptor 2 trafficking during retinal degeneration

Directory of Open Access Journals (Sweden)

Lin Yanhua

2012-02-01

Full Text Available Abstract Background Retinal degenerations, such as age-related macular degeneration (AMD and retinitis pigmentosa (RP, are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2 subunit and its trafficking may be modulated in retinal degenerations. Results Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD. We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1 and postsynaptic density protein 95 (PSD-95, were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites. Conclusions All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

Transplanting Retinal Cells using Bucky Paper for Support

Science.gov (United States)

Loftus, David J.; Cinke, Martin; Meyyappan, Meyya; Fishman, Harvey; Leng, Ted; Huie, Philip; Bilbao, Kalayaan

2004-01-01

A novel treatment for retinal degenerative disorders involving transplantation of cells into the eye is currently under development at NASA Ames Research Center and Stanford University School of Medicine. The technique uses bucky paper as a support material for retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, and/or stem cells. This technology is envisioned as a treatment for age-related macular degeneration, which is the leading cause of blindness in persons over age 65 in Western nations. Additionally, patients with other retinal degenerative disorders, such as retinitis pigmentosa, may be treated by this strategy. Bucky paper is a mesh of carbon nanotubes (CNTs), as shown in Figure 1, that can be made from any of the commercial sources of CNTs. Bucky paper is biocompatible and capable of supporting the growth of biological cells. Because bucky paper is highly porous, nutrients, oxygen, carbon dioxide, and waste can readily diffuse through it. The thickness, density, and porosity of bucky paper can be tailored in manufacturing. For transplantation of cells into the retina, bucky paper serves simultaneously as a substrate for cell growth and as a barrier for new blood vessel formation, which can be a problem in the exudative type of macular degeneration. Bucky paper is easily handled during surgical implantation into the eye. Through appropriate choice of manufacturing processes, bucky paper can be made relatively rigid yet able to conform to the retina when the bucky paper is implanted. Bucky paper offers a distinct advantage over other materials that have been investigated for retinal cell transplantation - lens capsule and Descemet's membrane - which are difficult to handle during surgery because they are flimsy and do not stay flat.

Retinal Detachment

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... 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 ...

Coincidence of retinitis pigmentosa and pseudoexfoliative glaucoma

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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.

Why pigs are free-roaming: Communities' perceptions, knowledge and practices regarding pig management and taeniosis/cysticercosis in a Taenia solium endemic rural area in Eastern Zambia.

Science.gov (United States)

Thys, Séverine; Mwape, Kabemba E; Lefèvre, Pierre; Dorny, Pierre; Phiri, Andrew M; Marcotty, Tanguy; Phiri, Isaac K; Gabriël, Sarah

2016-07-30

Taenia solium cysticercosis is a neglected parasitic zoonosis in many developing countries including Zambia. Studies in Africa have shown that the underuse of sanitary facilities and the widespread occurrence of free-roaming pigs are the major risk factors for porcine cysticercosis. Socio-cultural determinants related to free range pig management and their implications for control of T. solium remain unclear. The study objective was to assess the communities' perceptions, reported practices and knowledge regarding management of pigs and taeniosis/cysticercosis (including neurocysticercosis) in an endemic rural area in Eastern Zambia, and to identify possible barriers to pig related control measures such as pig confinement. A total of 21 focus group discussions on pig husbandry practices were organized separately with men, women and children, in seven villages from Petauke district. The findings reveal that the perception of pigs and their role in society (financial, agricultural and traditional), the distribution of the management tasks among the family members owning pigs (feeding, building kraal, seeking care) and environmental aspects (feed supply, presence of bush, wood use priorities, rainy season) prevailing in the study area affect pig confinement. People have a fragmented knowledge of the pork tapeworm and its transmission. Even if negative aspects/health risks of free-range pigs keeping are perceived, people are ready to take the risk for socio-economic reasons. Finally, gender plays an important role because women, and also children, seem to have a higher perception of the risks but lack power in terms of economic decision-making compared to men. Currently pig confinement is not seen as an acceptable method to control porcine cysticercosis by many farmers in Eastern Zambia, vaccination and treatment seemed to be more appropriate. Embedded in a One Health approach, disease control programs should therefore ensure a complementary appropriate set of control

Investigation on Live Pig Insurance and Ill Dead Pig Biosafety Disposal in Xinzheng,Henan Province%河南新郑市的生猪保险联动

Institute of Scientific and Technical Information of China (English)

刘炜; 张代宝; 贾松涛; 赵立军; 周婷婷

2014-01-01

Dead pig biosafety disposal is related to public health,food safety and sustainable and health development of animal husbandry. In order to make clear the situation of pig farming,dead pig biosafety disposal,live pig insur-ance and quarantine supervision in Xinzheng City,Henan Province,investigations were carried out on biosafety dis-posal and live pig insurance. The achievements and problems were analyzed,and suggestions were proposed on dead pig biosafety disposal.%文章介绍了河南新郑市推行生猪保险与病死猪无害化处理联动的情况和成效。针对这一工作存在的问题提出了建立联动机制的建议。

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

Inner neural retina loss in central retinal artery occlusion.

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Ikeda, Fumiko; Kishi, Shoji

2010-09-01

To report morphologic retinal changes and visual outcomes in acute and chronic central retinal artery occlusion (CRAO). We reviewed ten eyes of ten patients with CRAO (age, 65.3 ± 10.2 years) and measured retinal thicknesses at the central fovea and the perifovea using optical coherence tomography (OCT) over 8 ± 4 months. During the acute phase (within 10 days), the mean inner retinal thicknesses were 148% and 139% of normal values at 1 mm nasal and temporal to the fovea. They decreased to 22% and 11% of normal inner retinal thickness during the chronic phase (3 months or later). The retinal thickness at the perifovea decreased linearly until 3 months but was stable during the chronic phase. In contrast, the foveal thickness increased slightly in the acute phase but was equivalent to the normal level during the chronic phase. As a result of inner retinal atrophy, the foveal pit was shallow during the chronic phase. The final visual acuity was correlated positively with retinal thickness at the perifovea during the chronic CRAO phase. OCT showed that inner retinal necrosis with early swelling and late atrophy occurred in CRAO. The fovea and outer retina appeared to be excluded from ischemic change. The residual inner retina at the perifovea determined the final visual outcomes.

Multiple evanescent white dot syndrome associated with retinal vasculitis

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Takahashi A

2015-09-01

Full Text Available Akihiro Takahashi, Wataru Saito, Yuki Hashimoto, Susumu Ishida Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan Purpose: A recent study revealed thickening of the inner retinal layers in acute stage of multiple evanescent white dot syndrome (MEWDS; however, the pathogenesis is still unknown. We report two cases with MEWDS whose funduscopy showed obvious retinal vasculitis. Methods: Case reports. Results: Healthy myopic 16- and 27-year-old women were the cases under study. In both cases, funduscopic examination revealed multiple, faint, small, subretinal white dots at the posterior pole to the midperiphery and macular granularity oculus dexter. Retinal vascular sheathing was also observed at midperiphery. Late-phase fluorescein angiography revealed leakages corresponding to the vascular sheathing. Enhanced depth imaging optical coherence tomography revealed the discontinuity of the ellipsoid zone corresponding to the white dots and increased macular choroidal thickness. One month later, these white dots and retinal sheathing spontaneously resolved in both cases. Three months later, impairments of the outer retinal morphology and the visual acuity were restored. Conclusion: These results suggest that retinal vasculitis possibly plays a role in the pathogenesis of thickened inner retinal layers in acute stage of MEWDS. Keywords: enhanced depth imaging optical coherence tomography, choroidal thickness, inner retinal layer, retinal vascular sheathing

[Prevention of retinal detachment and treatment of retinoschisis].

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Messmer, E P

1990-01-01

The necessity for prophylactic treatment for degenerative disease in the peripheral retina cannot be evaluated merely on the basis of the ophthalmoscopic findings. Factors such as the patient's history, refraction, the status of the vitreous, and prospective future cataract extraction all have a major impact on the risk of developing retinal detachment. The latter condition can be classified in to three groups: (1) low risk (patients with no history of retinal detachment, intraocular surgery or posterior vitreous detachment, myopia less than three diopters): treatment of atrophic holes and lattice degeneration is not justified, treatment of flap tears according to the circumstances; (2) medium risk (patients with no history of retinal or posterior vitreous detachment; however, myopia of more than three diopters and/or aphakia): the treatment of lattice degeneration is not justified; treatment of breaks according to the circumstances; (3) high risk: (patients with symptoms of posterior vitreous detachment): the treatment of lattice degeneration and atrophic holes is not justified: treatment of tears is necessary; fellow eyes: the treatment of retinal breaks is necessary; treatment of lattice degeneration seems advisable in cases with bilateral symmetric findings or prior to cataract extraction. Treatment of senile retinoschisis is only justified in cases with large and centrally located holes in the outer wall or in the presence of symptomatic schisis detachment.

Immunization of pigs against infection with Schistosoma japonicum using ultraviolet-attenuated cercariae

International Nuclear Information System (INIS)

Shi, Y.-E.; Jiang, C.-F.; Han, J.-J.; Li, Y.-L.

1993-01-01

Since pigs are important in the zoonotic transmission of schistosomiasis japonica in China, a veterinary vaccine might contribute to the control of the disease in humans. Pigs were immunized with three doses each of 10 000 cercariae of Schistosoma japonicum attenuated with ultraviolet light (400 μWatt.min/cm 2 ). The experiment was performed with portable irradiation equipment in a rural area of the Hubei Province (P.R. China). A challenge infection of 1000 untreated cercariae was given 2.5 or 6 months after the last immunization, and age-matched naive pigs were challenged as a control. Immunized pigs developed about 90% resistance against the challenge. The liver egg load of these animals was reduced by over 90%. Less than 0.01% of the immunizing cercariae developed to adult parasites and the vaccination had no apparent adverse influence on the pig's health. (Author)

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...

Posterior vitreous detachment - prevalence of and risk factors for retinal tears

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Bond-Taylor M

2017-09-01

Full Text Available Martin Bond-Taylor,1 Gunnar Jakobsson,1,2 Madeleine Zetterberg1,2 1Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, 2Department of Clinical Neuroscience/Ophthalmology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden Purpose: The present study aimed to describe clinical characteristics of patients with posterior vitreous detachment (PVD, to determine the prevalence of retinal tears in PVD patients, and to find predictors for retinal tears in this patient group. Methods: Retrospective analysis of medical records on patients diagnosed with PVD, retinal tears, or vitreous hemorrhage at the Department of Ophthalmology at Sahlgrenska University Hospital, a tertiary eye center. Results: Between February and July 2009, 365 patients consulted the Department of Ophthalmology for PVD-related symptoms. The incidence of retinal tears was 14.5% (n=53 and that of vitreous and/or retinal hemorrhage was 22.7% (n=83. For analysis of possible predictors for complications to PVD, patients diagnosed with retinal tears or vitreous hemorrhage between May and July 2009 were also included in the study, resulting in a total of 426 patients. Predictors of a retinal tear were symptoms of visual impairment (P=0.024, the presence of vitreous or retinal hemorrhage at examination (P<0.001, and a duration of symptoms for <24 hours (P=0.004. Symptoms of flashes did not constitute an extra risk of retinal tears (P=0.135. Subsequent retinal pathology (follow-up time 4.5 years, including vitreous detachment/hemorrhage or retinal tears/detachment, occurred more often in patients presenting with a retinal tear. For patients with a retinal tear, the relative risk of having a retinal detachment in the same eye during the follow-up time was 17.7 when compared to patients without a retinal tear (risk ratio 17.7, 95% confidence interval 2.2–145. Conclusion: Patients seeking care on the first day have a

Evaluation of Ebola Virus Countermeasures in Guinea Pigs.

Science.gov (United States)

Marzi, Andrea

2017-01-01

Ebola virus (EBOV) pathology in humans remains incompletely understood; therefore, a number of rodent and nonhuman primate (NHP) models have been established to study the disease caused by this virus. While the macaque model most accurately recapitulates human disease, rodent models, which display only certain aspects of human disease but are more cost-effective, are widely used for initial screens during EBOV countermeasure development. In particular, mice and guinea pigs were among the first species used for the efficacy testing of EBOV vaccines and therapeutics. While mice have low predictive value, guinea pigs have proven to be a more reliable predictor for the evaluation of countermeasures in NHPs. In addition, guinea pigs are larger in size compared to mice, allowing for more frequent collection of blood samples at larger volumes. However, guinea pigs have the disadvantage that there is only a limited pool of immunological tools available to characterize host responses to vaccination, treatment and infection. In this chapter, the efficacy testing of an EBOV vaccine and a therapeutic in the guinea pig model are described.

Dexamethasone Implant (Ozurdex in a Case with Unilateral Simultaneous Central Retinal Vein and Branch Retinal Artery Occlusion

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Taylan Ozturk

2015-02-01

Full Text Available Simultaneous branch retinal artery and vein occlusion is a rare condition that may cause severe visual loss, and its treatment is often unrewarding. Herein, we report a case with simultaneous central retinal vein and branch retinal artery occlusion; it was successfully treated with a single dexamethasone intravitreal implant. The affected eye attained a visual acuity level of 20/25 from the visual acuity of hand motions at presentation with a residual, but relatively diminished, altitudinal scotoma during a follow-up period of 6 months.

Influence of genotype and feeding strategy on pig performance, plasma concentrations of micro nutrients, immune responses and faecal microbiota composition of growing-finishing pigs in a forage-based system

DEFF Research Database (Denmark)

Kongsted, Anne Grete; Nørgaard, Jan Værum; Jensen, Søren Krogh

2015-01-01

In free-range pig production it is important to reduce the input of nutrients from supplementary feed to reduce nutrient leaching and improve the resource efficiency of the system. A promising development might be to encourage foraging behaviour of the pigs. However, very little is known about pi...... significantly to the nutritional supply of pigs fed restrictedly with supplementary feed. There are indications that the mineral content of the premix is not needed in a forage-based free-range system but cautious need to be taken with regards to the vitamin A, D, E supply.......In free-range pig production it is important to reduce the input of nutrients from supplementary feed to reduce nutrient leaching and improve the resource efficiency of the system. A promising development might be to encourage foraging behaviour of the pigs. However, very little is known about pigs......) of either a traditional (Tamworth×(Landrace×Yorkshire)) or a ‘modern’ crossbreed (Duroc×(Landrace×Yorkshire)) fed a pelleted diet as supplementary feed either according to recommendations (NORM), or restrictedly with (RES+) or without (RES–) a supplementary vitamin and mineral mixture. The pigs ‘strip...

Protective effect of a polyvalent influenza DNA vaccine in pigs

DEFF Research Database (Denmark)

Karlsson, Ingrid; Borggren, Marie; Rosenstierne, Maiken Worsøe

2018-01-01

Background Influenza A virus in swine herds represents a major problem for the swine industry and poses a constant threat for the emergence of novel pandemic viruses and the development of more effective influenza vaccines for pigs is desired. By optimizing the vector backbone and using a needle...... needle-free delivery to the skin, we immunized pigs with two different doses (500 μg and 800 μg) of an influenza DNA vaccine based on six genes of pandemic origin, including internally expressed matrix and nucleoprotein and externally expressed hemagglutinin and neuraminidase as previously demonstrated....... Two weeks following immunization, the pigs were challenged with the 2009 pandemic H1N1 virus. Results When challenged with 2009 pandemic H1N1, 0/5 vaccinated pigs (800 μg DNA) became infected whereas 5/5 unvaccinated control pigs were infected. The pigs vaccinated with the low dose (500 μg DNA) were...

Low Birth Weight Impairs Acquisition of Spatial Memory Task in Pigs

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Sanne Roelofs

2018-06-01

Full Text Available In commercial pig farming, an increasing number of low birth weight (LBW piglets are born, due to selection for large litter sizes. While LBW piglets have a higher risk of pre-weaning mortality, a considerable number of these piglets survive to slaughter age. In humans, LBW is a risk factor for long-term cognitive impairments. In pigs, studies examining the post-weaning effects of LBW on cognition have reported contradictory results. Therefore, the current study aimed to assess the effects of LBW on cognitive development in pigs using an improved study design, by (1 testing a larger sample size than previous studies, (2 assessing acute and chronic stress responses to account for a potential altered stress response in LBW pigs, and (3 testing both female and male pigs to account for potential confounding effects of sex. Learning and memory of 20 LBW pigs and 20 normal birth weight (NBW pigs, both groups consisting of 10 females and 10 males, were compared using a spatial holeboard task. In this task, pigs had to learn and remember the locations of hidden food rewards. After a pig had successfully acquired the task, it was presented with two successive reversal phases during which it was presented with a new configuration of reward locations. The holeboard allows for simultaneous assessment of working and reference memory, as well as measures of motivation, exploration, and behavioral flexibility. Mixed model ANOVAs revealed a transiently impaired reference memory performance of LBW pigs, implying they had more difficulty learning their reward configuration in the holeboard. Also, LBW piglets showed increased pre-weaning hair cortisol concentrations compared to their NBW siblings. No other effects of LBW were found. Sex had no direct or interaction effects on any measures of holeboard performance or stress. It is possible that the enriched housing conditions applied during our study had an ameliorating effect on our pigs' cognitive development

Bilateral acute retinal necrosis after herpetic meningitis

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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

End-to-End Adversarial Retinal Image Synthesis.

Science.gov (United States)

Costa, Pedro; Galdran, Adrian; Meyer, Maria Ines; Niemeijer, Meindert; Abramoff, Michael; Mendonca, Ana Maria; Campilho, Aurelio

2018-03-01

In medical image analysis applications, the availability of the large amounts of annotated data is becoming increasingly critical. However, annotated medical data is often scarce and costly to obtain. In this paper, we address the problem of synthesizing retinal color images by applying recent techniques based on adversarial learning. In this setting, a generative model is trained to maximize a loss function provided by a second model attempting to classify its output into real or synthetic. In particular, we propose to implement an adversarial autoencoder for the task of retinal vessel network synthesis. We use the generated vessel trees as an intermediate stage for the generation of color retinal images, which is accomplished with a generative adversarial network. Both models require the optimization of almost everywhere differentiable loss functions, which allows us to train them jointly. The resulting model offers an end-to-end retinal image synthesis system capable of generating as many retinal images as the user requires, with their corresponding vessel networks, by sampling from a simple probability distribution that we impose to the associated latent space. We show that the learned latent space contains a well-defined semantic structure, implying that we can perform calculations in the space of retinal images, e.g., smoothly interpolating new data points between two retinal images. Visual and quantitative results demonstrate that the synthesized images are substantially different from those in the training set, while being also anatomically consistent and displaying a reasonable visual quality.

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.

Screening retinal transplants with Fourier-domain OCT

Science.gov (United States)

Rao, Bin

2009-02-01

Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

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Eui Seok Shin

Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs.

Science.gov (United States)

Kobinger, Gary P; Leung, Anders; Neufeld, James; Richardson, Jason S; Falzarano, Darryl; Smith, Greg; Tierney, Kevin; Patel, Ami; Weingartl, Hana M

2011-07-15

(See the editorial commentary by Bausch, on pages 179-81.) Reston ebolavirus was recently detected in pigs in the Philippines. Specific antibodies were found in pig farmers, indicating exposure to the virus. This important observation raises the possibility that pigs may be susceptible to Ebola virus infection, including from other species, such as Zaire ebolavirus (ZEBOV), and can transmit to other susceptible hosts. This study investigated whether ZEBOV, a species commonly reemerging in central Africa, can replicate and induce disease in pigs and can be transmitted to naive animals. Domesticated Landrace pigs were challenged through mucosal exposure with a total of 1 ×10(6) plaque-forming units of ZEBOV and monitored for virus replication, shedding, and pathogenesis. Using similar conditions, virus transmission from infected to naive animals was evaluated in a second set of pigs. Following mucosal exposure, pigs replicated ZEBOV to high titers (reaching 10(7) median tissue culture infective doses/mL), mainly in the respiratory tract, and developed severe lung pathology. Shedding from the oronasal mucosa was detected for up to 14 days after infection, and transmission was confirmed in all naive pigs cohabiting with inoculated animals. These results shed light on the susceptibility of pigs to ZEBOV infection and identify an unexpected site of virus amplification and shedding linked to transmission of infectious virus.

Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone

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Tomomi Masuda

2017-01-01

Full Text Available Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD, glaucoma, diabetic retinopathy (DR, and retinal vein occlusion (RVO. An excess amount of reactive oxygen species (ROS can lead to functional and morphological impairments in retinal pigment epithelium (RPE, endothelial cells, and retinal ganglion cells (RGCs. Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.

Tangential vitreous traction: a possible mechanism of development of cystoid macular edema in retinitis pigmentosa

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Mikiko Takezawa

2011-02-01

Full Text Available Mikiko Takezawa, Soichi Tetsuka, Akihiro KakehashiDepartment of Ophthalmology, Jichi Medical University, Saitama Medical Center, Saitama, Saitama, JapanAbstract: We report the possible mechanism of development of cystoid macular edema (CME in retinitis pigmentosa (RP in the case of a 68-year-old woman with RP and CME in the right eye and resolving CME in the left eye. Spectral domain optical coherence tomography showed CME and posterior vitreoschisis in the nasal quadrant of the fundus without a posterior vitreous detachment (PVD. This vitreous pathology suggested bilateral thickening and shrinkage of the posterior vitreous cortex. In the right eye, CME was evident with no vitreofoveal separation. However, in the left eye, minimal change was seen in the CME associated with a focal shallow PVD over the fovea. The best-corrected visual acuity (BCVA in the left eye increased to 0.3 from 0.15 7 years after the first visit. Tangential vitreous traction on the macula may have caused the CME in the right eye. The shallow PVD over the fovea might have released the tangential vitreous traction from the fovea, induced spontaneous resolution of the CME, and improved the BCVA in the left eye.Keywords: retinitis pigmentosa, cystoid macular edema, posterior vitreous detachment, posterior vitreoschisis, optical coherence tomography

Dietary Iron Repletion following Early-Life Dietary Iron Deficiency Does Not Correct Regional Volumetric or Diffusion Tensor Changes in the Developing Pig Brain

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Austin T. Mudd

2018-01-01

Full Text Available BackgroundIron deficiency is the most common micronutrient deficiency worldwide and children are at an increased risk due to the rapid growth occurring during early life. The developing brain is highly dynamic, requires iron for proper function, and is thus vulnerable to inadequate iron supplies. Iron deficiency early in life results in altered myelination, neurotransmitter synthesis, neuron morphology, and later-life cognitive function. However, it remains unclear if dietary iron repletion after a period of iron deficiency can recover structural deficits in the brain.MethodTwenty-eight male pigs were provided either a control diet (CONT; n = 14; 23.5 mg Fe/L milk replacer or an iron-deficient diet (ID; n = 14; 1.56 mg Fe/L milk replacer for phase 1 of the study, from postnatal day (PND 2 until 32. Twenty pigs (n = 10/diet from phase 1 were used in phase 2 of the study from PND 33 to 61, all pigs were provided a common iron sufficient diet, regardless of their early-life dietary iron status. All pigs remaining in the study were subjected to magnetic resonance imaging (MRI at PND 32 and again at PND 61 using structural imaging sequences and diffusion tensor imaging (DTI to assess volumetric and microstructural brain development, respectively. Data were analyzed using a two-way ANOVA to assess the main and interactive effects of early-life iron status and time.ResultsAn interactive effect was observed for absolute whole brain volumes, in which whole brain volumes of ID pigs were smaller at PND 32 but were not different than CONT pigs at PND 61. Analysis of brain region volumes relative to total brain volume indicated interactive effects (i.e., diet × day in the cerebellum, olfactory bulb, and putamen-globus pallidus. Main effects of early-life iron status, regardless of imaging time point, were noted for decreased relative volumes of the left hippocampus, right hippocampus, thalamus, and increased relative white matter volume

Integrated resource-driven pig production systems in a mountainous area of Northeast India: production practices and pig performance.

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Kumaresan, A; Bujarbaruah, K M; Pathak, K A; Das, Anubrata; Bardoloi, R K

2009-10-01

Data on pig production system was derived through structured household interviews from a total number of 320 rural households and performance of pigs was assessed. Results revealed that the pig production system represented mixed farming based mainly on the common property resources. Majority of the pigs were reared in intensive system and fed with home made cooked feed (kitchen waste and locally available plants). The body weight of crossbred, Burmese and local pigs were 67, 65.4 and 45.6 kg, respectively at 12 months of age with average daily body weight of 184, 179 and 125 g, respectively. The overall mortality among the pigs was 17.96%. The major causes of mortality in pigs were Swine fever, Swine erysipelas, digestive disorders, nephritis and respiratory disorders. The body weight gain in pigs subjected to deworming and mineral mixture supplementation (218 g/day) was significantly (p pigs, while the corresponding ratio for local pigs was 1:1.2. It is inferred that the smallholder resource driven pig production system is economically viable and sustainable at household level and there is enough scope to improve the smallholder resource driven pig production system.

Infection of guinea pigs with vesicular stomatitis New Jersey virus Transmitted by Culicoides sonorensis (Diptera: Ceratopogonidae).

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Pérez De León, Adalberto A; O'Toole, Donal; Tabachnick, Walter J

2006-05-01

Intrathoracically inoculated Culicoides sonorensis Wirth & Jones were capable of transmitting vesicular stomatitis New Jersey virus (family Rhabdoviridae, genus Vesiculovirus, VSNJV) during blood feeding on the abdomen of six guinea pigs. None of the guinea pigs infected in this manner developed clinical signs of vesicular stomatitis despite seroconversion for VSNJV. Guinea pigs infected by intradermal inoculations of VSNJV in the abdomen also failed to develop clinical signs of vesicular stomatitis. Three guinea pigs given intradermal inoculations of VSNJV in the foot pad developed lesions typical of vesicular stomatitis. Transmission by the bite of C. sonorensis may have facilitated guinea pig infection with VSNJV because a single infected C. sonorensis caused seroconversion and all guinea pigs infected by insect bite seroconverted compared with 50% of the guinea pigs infected by intradermal inoculation with a higher titer VSNJV inoculum. The role of C. sonorensis in the transmission of VSNJV is discussed.

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. ...

Surgical and visual outcomes of retinal detachment surgery in eyes with chorio-retinal coloboma

International Nuclear Information System (INIS)

Zafar, S.A.; Qureshi, N.A.; Pathan, A.H.K.

2016-01-01

Objective: To evaluate the anatomical and visual outcome of surgical management of retinal detachment associated with chorio-retinal coloboma. Study Design: Prospective interventional case series Place and Duration of Study: This study was conducted at Al-Shifa Trust Eye Hospital Rawalpindi from Jan 2012 to Dec 2013. Material and Methods: Twenty one eyes (21 patients) that underwent surgery for retinal detachment associated with chorio-retinal colobomas were selected. Evaluation was done on the basis of type of intervention, final visual acuity and anatomical outcome and complications. Out of 21, 19(90.47 percent) eyes underwent pars plana vitrectomy with silicone oil (SO) and 2(9.52 percent) underwent primary scleral buckling surgery. SO was removed in 9 (47.36 percent) eyes at final follow up. Encircling band was placed in 12 (63.15 percent) eyes based on peroperative judgment of surgeon. Intra-operative lensectomy was performed in 6 (28.57 percent) eyes. The main outcome measures were retinal re-attachment and visual recovery. Statistical analysis was performed using IBM statistical package for social sciences (SPSS) Statistics (version 17.0, Chicago, Illinois, USA). Qualitative variables were described using percentage; quantitative data were defined using mean +- standard deviation. The pre op and post op frequency of best corrected visual acuity (BVA) was compared using Wilcoxan Signed Ranks Test. Confidence interval was 95 percent (level of significance p<0.05). Results: The mean number of operations per eye were 1.57+- 0.74; mean follow-up was 13.1 months (range 12-18). The retina remained attached in 18 eyes (85.71 percent) at final follow-up. The post op BCVA improved significantly as compared to pre op BCVA (p< 0.01). Mean pre op BCVA was counting fingers (CF) and mean post op value of BCVA was 3/60. Conclusion: Pars plana vitrectomy along with silicon oil tamponade for retinal detachment related to choroiretinal coloboma improves the long

Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases.

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Madeira, Maria H; Boia, Raquel; Santos, Paulo F; Ambrósio, António F; Santiago, Ana R

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

Low Vision Rehabilitation of Retinitis Pigmentosa. Practice Report

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Rundquist, John

2004-01-01

Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…

Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

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Barbero, Ana M; Frasch, H Frederick

2009-02-01

Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (Ppig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (Pguinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, Ppig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3guinea pig skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.

Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats☆

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Li, Guang; Garza, Bryan De La; Shih, Yen-Yu I.; Muir, Eric R.; Duong, Timothy Q.

2013-01-01

The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 × 44 × 600 μm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution. PMID:22721720

Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats.

Science.gov (United States)

Li, Guang; De La Garza, Bryan; Shih, Yen-Yu I; Muir, Eric R; Duong, Timothy Q

2012-08-01

The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 × 44 × 600 μm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution. Copyright © 2012 Elsevier Ltd. All rights reserved.

Retinal adaptation to dim light vision in spectacled caimans (Caiman crocodilus fuscus): Analysis of retinal ultrastructure.

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Karl, Anett; Agte, Silke; Zayas-Santiago, Astrid; Makarov, Felix N; Rivera, Yomarie; Benedikt, Jan; Francke, Mike; Reichenbach, Andreas; Skatchkov, Serguei N; Bringmann, Andreas

2018-05-19

It has been shown that mammalian retinal glial (Müller) cells act as living optical fibers that guide the light through the retinal tissue to the photoreceptor cells (Agte et al., 2011; Franze et al., 2007). However, for nonmammalian species it is unclear whether Müller cells also improve the transretinal light transmission. Furthermore, for nonmammalian species there is a lack of ultrastructural data of the retinal cells, which, in general, delivers fundamental information of the retinal function, i.e. the vision of the species. A detailed study of the cellular ultrastructure provides a basic approach of the research. Thus, the aim of the present study was to investigate the retina of the spectacled caimans at electron and light microscopical levels to describe the structural features. For electron microscopy, we used a superfast microwave fixation procedure in order to achieve more precise ultrastructural information than common fixation techniques. As result, our detailed ultrastructural study of all retinal parts shows structural features which strongly indicate that the caiman retina is adapted to dim light and night vision. Various structural characteristics of Müller cells suppose that the Müller cell may increase the light intensity along the path of light through the neuroretina and, thus, increase the sensitivity of the scotopic vision of spectacled caimans. Müller cells traverse the whole thickness of the neuroretina and thus may guide the light from the inner retinal surface to the photoreceptor cell perikarya and the Müller cell microvilli between the photoreceptor segments. Thick Müller cell trunks/processes traverse the layers which contain light-scattering structures, i.e., nerve fibers and synapses. Large Müller cell somata run through the inner nuclear layer and contain flattened, elongated Müller cell nuclei which are arranged along the light path and, thus, may reduce the loss of the light intensity along the retinal light path. The

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

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Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

[Stickler's syndrome (dystrophia vitreoretinalis hereditaria). Results of surgery for retinal detachment].

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Karel, I; Dolezalová, J; Oudová, P

2001-05-01

Stickler's syndrome (SS) is an autosomal dominant hereditary disease of the collagenous connective tissue where impaired development of the vitreous body gel and peripheral retina and detachment of the retina are associated with general manifestations. The objective of the retrospective study was to evaluate the long-term results of surgery of retinal detachment in SS. The group of patients comprised 7 patients, 6 men and 1 woman aged 4 to 45 years, average age 16.8 years. Autosomal dominant heredity was obvious in 6 members (85.7%) of two families. General manifestations of SS included abnormalities of the facial skeleton (6 patients), cleft palate (4 patients), impaired hearing (2 patients), marfanoid habitus (2 patients) and hyperextensibility of the joints (4 patients). In the eyes with SS was manifested by myopia from -1 to -9 D and a liquid vitreous body. Multiple foci of lattice degeneration supplemented the finding in 6 patients (85.7%). Detachment of the retina was a manifestation of SS in 12 of 14 eyes (85.7%). It was manifested in 5 of 7 patients concurrently or within 12 years in both eyes. The causes of retinal detachment were multiple equatorial and postequatorial tears due to lattice degeneration in 8 eyes (66.7%) or a giant tear in 4 eyes (33.3%). Advanced proliferative vitreoretinopathy (PVR) was associated with retinal detachment in 8 eyes (66.7%) and in 6 eyes (50%) it was not possible to assess the beginning of retinal detachment. In 3 of 5 patients with bilateral retinal detachment the adverse course of retinal detachment on the first eye was followed 8 to 12 years previously in another department: two retinal detachments with giant tears were evaluated as inoperable and one inveterated detachment with advanced PVR was operated unsuccessfully. Retinal detachment was operated in 9 eyes of 7 patients, in two patients both eyes were operated simultaneously. The patients were followed up after surgery for 11 months to 15 years, on average for 65

Vision deficits precede structural losses in a mouse model of mitochondrial dysfunction and progressive retinal degeneration.

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Laliberté, Alex M; MacPherson, Thomas C; Micks, Taft; Yan, Alex; Hill, Kathleen A

2011-12-01

Current animal models of retinal disease often involve the rapid development of a retinal disease phenotype; however, this is at odds with age-related diseases that take many years to manifest clinical symptoms. The present study was performed to examine an apoptosis-inducing factor (Aif)-deficient model, the harlequin carrier mouse (X(hq)X), and determine how mitochondrial dysfunction and subsequent accelerated aging affect the function and structure of the mouse retina. Vision and eye structure for cohorts of 6 X(hq)X and 6 wild type mice at 3, 11, and 15 months of age were studied using in vivo electroretinography (ERG), and optical coherence tomography (OCT). Retinal superoxide levels were determined in situ using dihydroethidium (DHE) histochemistry. Retinal cell counts were quantified post mortem using hematoxylin and eosin (H&E) staining. ERG analysis of X(hq)X retinal function indicated a reduction in b-wave amplitude significant at 3 months of age (p retina (p retina may account for the early and significant reduction in retinal function. This remodeling of retinal neurochemistry in response to stress may be a relevant mechanism in the progression of normal retinal aging and early stages of some retinal degenerative diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Validation of pig operations through pipelines

Energy Technology Data Exchange (ETDEWEB)

Tolmasquim, Sueli Tiomno [TRANSPETRO - PETROBRAS Transporte S.A., Rio de Janeiro, RJ (Brazil); Nieckele, Angela O. [Pontificia Univ. Catolica do Rio de Janeiro, RJ (Brazil). Dept. de Engenharia Mecanica

2005-07-01

In the oil industry, pigging operations in pipelines have been largely applied for different purposes: pipe cleaning, inspection, liquid removal and product separation, among others. An efficient and safe pigging operation requires that a number of operational parameters, such as maximum and minimum pressures in the pipeline and pig velocity, to be well evaluated during the planning stage and maintained within stipulated limits while the operation is accomplished. With the objective of providing an efficient tool to assist in the control and design of pig operations through pipelines, a numerical code was developed, based on a finite difference scheme, which allows the simulation of two fluid transient flow, like liquid-liquid, gas-gas or liquid-gas products in the pipeline. Modules to automatically control process variables were included to employ different strategies to reach an efficient operation. Different test cases were investigated, to corroborate the robustness of the methodology. To validate the methodology, the results obtained with the code were compared with a real liquid displacement operation of a section of the OSPAR oil pipeline, belonging to PETROBRAS, with 30'' diameter and 60 km length, presenting good agreement. (author)

Pig model for diabetes

DEFF Research Database (Denmark)

2016-01-01

The present invention relates to a transgenic pig comprising a mutated IAPP gene and displaying a phenotype associated with diabetes. The invention also relates to a transgenic blastocyst, embryo, fetus, donor cell and/or cell nucleusderived from said transgenic pig. The invention further relates...... to use of the transgenic pig as a model system for studying therapy, treatment and/or prevention of diabetes....

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.

Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

International Nuclear Information System (INIS)

Isom, H.C.; Mummaw, J.; Kreider, J.W.

1983-01-01

Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

Science.gov (United States)

Ikeda, Yasuhiro; Nishiguchi, Koji M; Miya, Fuyuki; Shimozawa, Nobuhiro; Funatsu, Jun; Nakatake, Shunji; Fujiwara, Kohta; Tachibana, Takashi; Murakami, Yusuke; Hisatomi, Toshio; Yoshida, Shigeo; Yasutomi, Yasuhiro; Tsunoda, Tatsuhiko; Nakazawa, Toru; Ishibashi, Tatsuro; Sonoda, Koh-Hei

2018-02-01

To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

Peripheral retinal changes in highly myopic young Asian eyes.

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Chen, David Z; Koh, Victor; Tan, Marcus; Tan, Colin S; Nah, Gerard; Shen, Liang; Bhargava, Mayuri; Cheng, Ching-Yu; Zhao, Paul; Wong, Tien Yin; Saw, Seang-Mei

2018-03-25

To determine the type and prevalence of peripheral retinal changes and its relationship with axial length (AL) in a population of young Asian adult males. This was a cross-sectional study of male subjects aged between 19 and 25 years old. High myopes [spherical equivalent refraction, (SER) lattice degeneration (LD; n = 109, 14.6%) were the commonest findings, and their prevalence was significantly higher among high myopes (LD, 16.9% versus 5.8%; WWOP, 57.2% versus 5.8%; both p < 0.001). Among high myopes, temporal LD was more common (71%) and 35% had more than one area in the same eye. Increasing AL was associated with LD (odds ratio 1.28, p = 0.01) and retinal holes (odd's ratio 1.44, p = 0.02) on multivariate analysis. White without pressure (WWOP) and LD were the commonest peripheral retinal changes. One-third of high myopes with LD had more than one area in the same eye. Increasing AL was associated with LD and retinal holes. Studies in older adults should be conducted to develop clinical guidelines for the management of high myopes. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Delayed rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells

Science.gov (United States)

Weick, Michael; Demb, Jonathan B.

2011-01-01

SUMMARY Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5–10 mV) also suppressed firing during subsequent depolarization. This suppression was sensitive selectively to blockers of delayed-rectifier K channels (KDR). Somatic membrane patches showed TEA-sensitive KDR currents with activation near −25 mV and removal of inactivation at voltages negative to Vrest. Brief periods of hyperpolarization apparently remove KDR inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. PMID:21745646

A cascade model of information processing and encoding for retinal prosthesis.

Science.gov (United States)

Pei, Zhi-Jun; Gao, Guan-Xin; Hao, Bo; Qiao, Qing-Li; Ai, Hui-Jian

2016-04-01

Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases. Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue. Some retinal models have been presented, ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena. However, Most of these focus on stimulus image compression, edge detection and reconstruction, but do not generate spike trains corresponding to visual image. In this study, based on state-of-the-art retinal physiological mechanism, including effective visual information extraction, static nonlinear rectification of biological systems and neurons Poisson coding, a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward, which integrates both anatomic connections and functional computations of retina. Using MATLAB software, spike trains corresponding to stimulus image were numerically computed by four steps: linear spatiotemporal filtering, static nonlinear rectification, radial sampling and then Poisson spike generation. The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina, which is helpful in developing artificial retina for the retinally blind.

Comparison of retinal vascular geometry in obese and non-obese children.

Directory of Open Access Journals (Sweden)

Evelyn Li Min Tai

Full Text Available Childhood obesity is associated with adult cardiometabolic disease. We postulate that the underlying microvascular dysfunction begins in childhood. We thus aimed to compare retinal vascular parameters between obese and non-obese children.This was a cross-sectional study involving 166 children aged 6 to 12 years old in Malaysia. Ocular examination, biometry, retinal photography, blood pressure and body mass index measurement were performed. Participants were divided into two groups; obese and non-obese. Retinal vascular parameters were measured using validated software.Mean age was 9.58 years. Approximately 51.2% were obese. Obese children had significantly narrower retinal arteriolar caliber (F(1,159 = 6.862, p = 0.010, lower arteriovenous ratio (F(1,159 = 17.412, p < 0.001, higher venular fractal dimension (F(1,159 = 4.313, p = 0.039 and higher venular curvature tortuosity (F(1,158 = 5.166, p = 0.024 than non-obese children, after adjustment for age, gender, blood pressure and axial length.Obese children have abnormal retinal vascular geometry. These findings suggest that childhood obesity is characterized by early microvascular abnormalities that precede development of overt disease. Further research is warranted to determine if these parameters represent viable biomarkers for risk stratification in obesity.

Complex genetics of familial exudative vitreoretinopathy and related pediatric retinal detachments

Science.gov (United States)

Kondo, Hiroyuki

2015-01-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder that can cause various types of retinal detachments. The abnormalities in eyes with FEVR are caused by poor vascularization in the peripheral retina. The genetics of FEVR is highly heterogeneous, and mutations in the genes for Wnt signaling and a transcription factor have been reported to be responsible for FEVR. These factors have been shown to be the regulators of the pathophysiological pathways of retinal vascular development. Studies conducted to identify the causative genes of FEVR have uncovered a diverse and complex relationship between FEVR and other diseases; for example, Norrie disease, a Mendelian-inherited disease; retinopathy of prematurity, a multifactorial genetic disease; and Coats disease, a nongenetic disease, associated with pediatric retinal detachments. PMID:29018668

Prolonged Prevention of Retinal Degeneration with Retinylamine Loaded Nanoparticles

OpenAIRE

Puntel, Anthony; Maeda, Akiko; Golczak, Marcin; Gao, Song-Qi; Yu, Guanping; Palczewski, Krzysztof; Lu, Zheng-Rong

2015-01-01

Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amin...

Presentation of Complex Homozygous Allele in ABCA4 Gene in a Patient with Retinitis Pigmentosa

Directory of Open Access Journals (Sweden)

Māreta Audere

2015-01-01

Full Text Available Retinitis pigmentosa is a degenerative retinal disease characterized by progressive photoreceptor damage, which causes loss of peripheral and night vision and the development of tunnel vision and may result in loss of central vision. This study describes a patient with retinitis pigmentosa caused by a mutation in the ABCA4 gene with complex allele c.1622T>C, p.L541P; c.3113C>T, p.A1038V in homozygous state.

An improved method for lifting and transporting anesthetized pigs within an animal facility

DEFF Research Database (Denmark)

Schumacher-Petersen, Camilla; Hammelev, Karsten Pharao; Flescher, Jens Erik

2014-01-01

Transporting anesthetized pigs in a laboratory setting often requires strenuous manual lifting, posing a hazard to the safety of animal care personnel and to the welfare of the pigs. The authors developed an improved approach to lifting and transporting anesthetized pigs weighing up to 350 kg using...... mechanical lifts. Different equipment was used to accommodate pigs of different sizes as well as the building designs of three animal facilities. Using the lifts, anesthetized pigs are carried on sheets to maintain their comfort while being transported. The approach refines previous methods for handling...

A consonant construction of the hyaloid and retinal vascular systems by the angiogenic process.

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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).

A chick model of retinal detachment: cone rich and novel.

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Colleen M Cebulla

Full Text Available Development of retinal detachment models in small animals can be difficult and expensive. Here we create and characterize a novel, cone-rich retinal detachment (RD model in the chick.Retinal detachments were created in chicks between postnatal days 7 and 21 by subretinal injections of either saline (SA or hyaluronic acid (HA. Injections were performed through a dilated pupil with observation via surgical microscope, using the fellow eye as a control. Immunohistochemical analyses were performed at days 1, 3, 7, 10 and 14 after retinal detachment to evaluate the cellular responses of photoreceptors, Müller glia, microglia and nonastrocytic inner retinal glia (NIRG. Cell proliferation was detected with bromodeoxyuridine (BrdU-incorporation and by the expression of proliferating cell nuclear antigen (PCNA. Cell death was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL. As in mammalian models of RD, there is shortening of photoreceptor outer segments and mis-trafficking of photoreceptor opsins in areas of RD. Photoreceptor cell death was maximal 1 day after RD, but continued until 14 days after RD. Müller glia up-regulated glial fibriliary acidic protein (GFAP, proliferated, showed interkinetic nuclear migration, and migrated to the subretinal space in areas of detachment. Microglia became reactive; they up-regulated CD45, acquired amoeboid morphology, and migrated toward outer retina in areas of RD. Reactive NIRG cells accumulated in detached areas.Subretinal injections of SA or HA in the chick eye successfully produced retinal detachments and cellular responses similar to those seen in standard mammalian models. Given the relatively large eye size, and considering the low cost, the chick model of RD offers advantages for high-throughput studies.

Lycium barbarum polysaccharides reduce neuronal damage, blood-retinal barrier disruption and oxidative stress in retinal ischemia/reperfusion injury.