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

Science.gov (United States)

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

2015-01-01

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

Basement membrane abnormalities in human eyes with diabetic retinopathy

DEFF Research Database (Denmark)

Ljubimov, A V; Burgeson, R E; Butkowski, R J

1996-01-01

Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but alterations in individual BM components in diabetic eyes, especially in diabetic retinopathy (DR), are obscure. To identify abnormalities in the distribution of specific constituents, we analyzed cryostat sections...... of human eyes obtained at autopsy (seven normal, five diabetic without DR, and 13 diabetic with DR) by immunofluorescence with antibodies to 30 BM and extracellular matrix components. In non-DR eyes, no qualitative changes of ocular BM components were seen. In some DR corneas, epithelial BM was stained...... discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular...

The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

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Ghulam Mohammad

2013-01-01

Full Text Available This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2 inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas.

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Chintalapudi, Sumana R; Wang, XiaoFei; Li, Huiling; Lau, Yin H Chan; Williams, Robert W; Jablonski, Monica M

2016-01-01

Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina. Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes. In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans -acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5 , expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5-immunopositive cones were

Retina-Inspired Filter.

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Doutsi, Effrosyni; Fillatre, Lionel; Antonini, Marc; Gaulmin, Julien

2018-07-01

This paper introduces a novel filter, which is inspired by the human retina. The human retina consists of three different layers: the Outer Plexiform Layer (OPL), the inner plexiform layer, and the ganglionic layer. Our inspiration is the linear transform which takes place in the OPL and has been mathematically described by the neuroscientific model "virtual retina." This model is the cornerstone to derive the non-separable spatio-temporal OPL retina-inspired filter, briefly renamed retina-inspired filter, studied in this paper. This filter is connected to the dynamic behavior of the retina, which enables the retina to increase the sharpness of the visual stimulus during filtering before its transmission to the brain. We establish that this retina-inspired transform forms a group of spatio-temporal Weighted Difference of Gaussian (WDoG) filters when it is applied to a still image visible for a given time. We analyze the spatial frequency bandwidth of the retina-inspired filter with respect to time. It is shown that the WDoG spectrum varies from a lowpass filter to a bandpass filter. Therefore, while time increases, the retina-inspired filter enables to extract different kinds of information from the input image. Finally, we discuss the benefits of using the retina-inspired filter in image processing applications such as edge detection and compression.

Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina

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Sandra M. Cardona

2015-10-01

Full Text Available Fractalkine (CX3CL1 or FKN is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor CX3CR1 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of CX3CR1 in inflammatory-mediated damage to retinal neurons using a model of diabetic retinopathy. For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and diabetic (Ins2Akita CX3CR1-wild-type and CX3CR1-deficient mice at 10 and 20 weeks of age. Our results show that Ins2Akita CX3CR1-knockout mice exhibited (a decreased neuronal cell counts in the retinal ganglion cell layer, (b increased microglial cell numbers, and (c decreased astrocyte responses comparable with Ins2Akita CX3CR1-Wild-type mice at 20 weeks of age. Analyses of the inflammatory response using PCR arrays showed several inflammatory genes differentially regulated in diabetic tissues. From those, the response in Ins2Akita CX3CR1-deficient mice at 10 weeks of age revealed a significant upregulation of IL-1β at the transcript level that was confirmed by enzyme-linked immunosorbent assay in soluble retinal extracts. Overall, IL-1β, VEGF, and nitrite levels as a read out of nitric oxide production were abundant in Ins2Akita CX3CR1-deficient retina. Notably, double immunofluorescence staining shows that astrocytes act as a source of IL-1β in the Ins2Akita retina, and CX3CR1-deficient microglia potentiate the inflammatory response via IL-1β release. Collectively, these data demonstrate that dysregulated microglial responses in absence of CX3CR1 contribute to inflammatory-mediated damage of neurons in the diabetic retina.

Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas

Science.gov (United States)

Chintalapudi, Sumana R.; Wang, XiaoFei; Li, Huiling; Lau, Yin H. Chan; Williams, Robert W.; Jablonski, Monica M.

2016-01-01

Purpose Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina. Methods Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes. Results In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans-acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5, expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5

The retina

DEFF Research Database (Denmark)

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

2003-01-01

A prominent and early feature of the retinopathy of diabetes mellitus is a diffuse increase in vascular permeability. As the disease develops, the development of frank macular oedema may result in vision loss. That reactive oxygen species production is likely to be elevated in the retina, and tha...

Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats.

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Yang, Fang; Yu, Jinqiang; Ke, Feng; Lan, Mei; Li, Dekun; Tan, Ke; Ling, Jiaojiao; Wang, Ying; Wu, Kaili; Li, Dai

2018-03-29

To investigate the potential protective effects of curcumin on the retina in diabetic rats. An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating

Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

DEFF Research Database (Denmark)

Campos, Elisa J.; Martins, João; Brudzewsky, Dan

2018-01-01

1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model.  Methods: Type 1 DM was induced in male Wistar rats by an intraperitoneal injection of streptozotocin. Starting 2weeks after DM onset, animals were treated orally with sitagliptin (5...... of NPY to all receptors. Sitagliptin alone reduced retinal NPY mRNA levels. The effects of DM on the NPY system were not affected by sitagliptin.  Conclusion: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP...

Bipolar cell gap junctions serve major signaling pathways in the human retina.

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Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats.

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Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

2017-04-01

Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. In this experimental study, 16 male Wistar rats weighing 200 - 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina.

Role of VEGF-A in endothelial phenotypic shift in human diabetic retinopathy and VEGF-A-induced retinopathy in monkeys

NARCIS (Netherlands)

Hofman, P.; Blaauwgeers, H. G.; Vrensen, G. F.; Schlingemann, R. O.

2001-01-01

The endothelium-specific antigen PAL-E, associated with transport vesicles in non-barrier endothelium, is almost absent from barrier capillaries in the normal brain and retina. We have recently demonstrated that only leaking retinal capillaries in diabetic retinopathy (DR) in humans

Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas - a comparative study

DEFF Research Database (Denmark)

Christiansen, Anders Tolstrup; Kiilgaard, Jens Folke; Klemp, Kristian

2018-01-01

retinal signaling. These findings extend existing knowledge on NPY and NPY-expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY-ir cells described in the present study further highlights the potential importance of NPY......Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including...... humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy...

Pathological changes in the retina of eyes rats with experimental 2 type diabetes mellitus and their correction by oral gels with biologically active substances

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V. V. Vit

2014-07-01

Full Text Available Purpose: To study of therapeutic and prophylactic action on the retina of rats with experimental diabetes mellitus type 2 (DM2 oral mucosal gels containing biologically active substances (BAS.Methods: DM2 was induced by protamine method Ulyanov and Tarasova [2000]. As BAS used lysozyme, flour of grape leaves, the water extract of blueberries and quercetin. Mucosal gels containing active substances, applied to the mucous lining of the mouth for 2 weeks. The serum glucose concentration was performed and histological studies of the retina.Results: Application mucosal gels reduces BAS 8‑22 % glucose (most with blueberry extract and significantly improves retinal histology (vacuolar degeneration less pronounced ganglion cells, there are no structural changes in photoreceptor layer. Gels revealed more effective with containing extract of bilberry, grape flour and quercetin.Conclusion: Oral mucosal application of gels containing active substances, have protection of retina in diabetes mellitus type 2.

Modulation of microglia in the retina: new insights into diabetic retinopathy.

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Arroba, Ana I; Valverde, Ángela M

2017-06-01

During last decades, the diagnosis of diabetes has been associated with several chronic complications such as diabetic retinopathy (DR). Recent studies of DR have revealed an inflammatory component, which precedes the detection of alterations in the visual function. During DR, the inflammatory process presents two opposite roles depending on the polarization of resident immune cells of the retina triggering proinflammatory (M1) or antiinflammatory (M2) actions. In an early stage of DR, the M2 response concurs with the M1 and is able to ameliorate inflammation and delay the progression of the disease. However, during the progression of DR, the M1 response is maintained whereas the M2 declines and, in this scenario, the classical proinflammatory signaling pathways are chronically activated leading to retinal neurodegeneration and the loss of visual function. The M1/M2 responses are closely related to the activation and polarization of microglial cells. This review aims to offer an overview of the recent insights into the role of microglial cells during inflammation in DR. We have focused on the possibility of modulating microglia polarization as a new therapeutic strategy in DR treatments.

Effects of Chinese herbal medicines on the occurrence of diabetic retinopathy in type 2 diabetes patients and protection of ARPE-19 retina cells by inhibiting oxidative stress

Science.gov (United States)

Cheng, Chi-Fung; Ho, Tsung-Jung; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Li, Ju-Pi; Huang, Shao-Mei; Lin, Jung-Chun; Lin, Chih-Chien

2017-01-01

Diabetic retinopathy is a microvascular complication of type 2 diabetes and the leading cause of acquired blindness. In Taiwan, Chinese herbal medicine (CHM) is a popular adjunctive therapy. In this study, we investigated the CHM prescription patterns and their effects. We identified 23,701 subjects with type 2 diabetes in a database, and after matching for age and gender, 6,948 patients each were assigned to CHM and non-CHM groups. In the female subgroups, the cumulative retinopathy probability was lower for the CHM users than that for the CHM non-users (P herbs. CHM network analysis showed that JWXYS was the core CHM of cluster 1. JWXYS, DS, XF, and SZRT exhibited both of the reductions of H2O2-induced phosphorylation of p38 MAPK and p44/42 MAPK (Erk1/2) in human ARPE-19 retina cells. In cluster 2, SJHXT was the core CHM. SJHXT and NX showed both of the phosphorylation reductions. In cluster 3, GGT was the core CHM, and it reduced the phosphorylation of both MAPKs. In cluster 4, HQin was the core CHM, and it also reduced the phosphorylation of both MAPKs. Our study suggests that adjunctive CHM therapy may reduce diabetic retinopathy via antioxidant activity of the herbs and provides information on core CHM treatments for further scientific investigations or therapeutic interventions. PMID:28969009

Proteomic interactions in the mouse vitreous-retina complex.

Directory of Open Access Journals (Sweden)

Jessica M Skeie

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

Proteomic interactions in the mouse vitreous-retina complex.

Science.gov (United States)

Skeie, Jessica M; Mahajan, Vinit B

2013-01-01

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

Update on Diagnosis and Treatment of Diabetic Retinopathy: A Consensus Guideline of the Working Group of Ocular Health (Spanish Society of Diabetes and Spanish Vitreous and Retina Society)

OpenAIRE

Borja Corcóstegui; Santiago Durán; María Olga González-Albarrán; Cristina Hernández; José María Ruiz-Moreno; Javier Salvador; Patricia Udaondo; Rafael Simó

2017-01-01

A group of members of the Spanish Retina and Vitreous Society (SERV) and of the Working Group of Ocular Health of the Spanish Society of Diabetes (SED) updated knowledge regarding the diagnosis and treatment of diabetic retinopathy (DR) based on recent evidence reported in the literature. A synthesis of this consensus forms the basis of the present review, which is intended to inform clinicians on current advances in the field of DR and their clinical applicability to patients with this disea...

Zinc might protect oxidative changes in the retina and pancreas at the early stage of diabetic rats

International Nuclear Information System (INIS)

Moustafa, Sohair A.

2004-01-01

It is well documented that oxidative stress is a basic mechanism behind the development of diabetic retinopathy (DR). The current study was undertaken to elucidate the possible role of zinc as an antioxidant and a biological membrane stabilizer in the protection against (DR). Male Wistar rats weighing 250 ± 50 g were made diabetic by injection with a single ip dose of alloxan (100 mg/kg). Another group of rats was simultaneously treated with alloxan (100 mg/kg) and a single ip dose of zinc chloride (ZnCl 2 ) (5 mg/kg). Blood and tissue samples were collected at 24, 48, and 72 h post-treatment in both groups. Diabetic state was confirmed by the determination of plasma glucose levels (significantly elevated at any time of the experiment when compared with controls receiving vehicle). Plasma insulin was significantly increased 24 h after treatment in both alloxan and alloxan plus ZnCl 2 -treated groups, and then decreased markedly 48 and 72 h post treatment in both groups. Alloxan treatment depleted both retinal and liver glutathione contents. The decrease in retinal and liver GSH in alloxan-treated rats was accompanied with a sustained increase in their thiobarbituric acid (TBA) content. Simultaneous treatment of rats with alloxan and ZnCl 2 blunted the sustained increment in plasma glucose induced by alloxan. The combined administration of alloxan and zinc reversed the depleting effect on retinal and hepatic GSH in alloxan-treated rats and reduced the elevations in TBA content of both retinas and livers. At variance with many other antioxidants the current results clearly indicate the beneficial effects of Zn in both controlling hyperglycemia and the protection of the retina against oxidative stress in diabetes which may help set a new direction toward the development of effective treatments of DR

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

Science.gov (United States)

Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

2014-01-01

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

Science.gov (United States)

Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

2014-12-01

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas-A comparative study.

Science.gov (United States)

Christiansen, Anders Tolstrup; Kiilgaard, Jens Folke; Klemp, Kristian; Woldbye, David Paul Drucker; Hannibal, Jens

2018-04-17

Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy and 3D reconstructions, we found NPY to be expressed in GABAergic and calretinin-immunoreactive (-ir) amacrine cells of both species as well as parvalbumin-ir amacrine cells of humans. Furthermore, we identified at least two different types of medium- to wide-field NPY-ir amacrine cells. Finally, we detected likely synaptic appositions between the NPY-ir amacrine cells and melanopsin- and nonmelanopsin-ir ganglion cells, GABAergic and dopaminergic amacrine cells, rod bipolar cells, and horizontal cells, suggesting that NPY-ir cells play diverse roles in modulation of both image and non-image forming retinal signaling. These findings extend existing knowledge on NPY and NPY-expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY-ir cells described in the present study further highlights the potential importance of NPY signaling in retinal function. © 2018 Wiley Periodicals, Inc.

Pathological alterations typical of human Tay-Sachs disease, in the retina of a deep-sea fish

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Fishelson, L.; Delarea, Yacov; Galil, Bella S.

Micrographs of retinas from the deep-sea fish Cataetyx laticeps revealed visual cells containing membranous whorls in the ellipsoids of the inner segments resulting from stretching and modifications of the mitochondria membranes and their cristae. These pathological structures seem to be homologous to the whorls observed in retinas of human carriers of Tay-Sachs disease. This disease, a genetic disorder, is found in humans and some mammals. Our findings in fish suggest that the gene responsible can be found throughout the vertebrate evolutionary tree, possibly dormant in most taxa.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model

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Rui-Jin Ran

2016-11-01

Full Text Available AIM: To examine the expression of high mobility group box-1 (HMGB-1 and intercellular adhesion molecule-1 (ICAM-1 in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB and blood-brain barrier (BBB in a rat model of type 2 diabetes. METHODS: The type-2 diabetes mellitus (DM model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ. Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA. RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P＜0.01. The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA, total cholesterol (TC, total triglycerides (TG and low density lipoprotein cholesterol (LDL-C in the DM rats significantly higher than those in the controls (all P＜0.01. HMGB-1 (0.96±0.03, P＜0.01 and ICAM-1 (0.76±0.12, P＜0.05 levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13, P＜0.01 and ICAM-1 (1.15±0.08, P＜0.01 levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P＜0.01. However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats. CONCLUSION: BRB permeability increases significantly

Increased Expression of Intercellular Adhesion Molecule-1, Vascular Cellular Adhesion Molecule-1 and Leukocyte Common Antigen in Diabetic Rat Retina

Institute of Scientific and Technical Information of China (English)

Ningyan Bai; Shibo Tang; Jing Ma; Yan Luo; Shaofeng Lin

2003-01-01

Purpose: To understand the expression and distribution of intercellular adhesion molecule- 1(ICAM- 1),vascular cellular adhesion molecule- 1 (VCAM- 1)and CD45 (Leukocyte Common Antigen) in the control nondiabetic and various courses of diabetic rats retina. To explore the role of adhesion molecules (Ams) and the adhesion of leukocytes to vascular endothelial cells via Ams in diabetic retinopathy(DR).Methods: Sixty healthy adult male Wistar rats were randomly divided into diabetic groups(induced by Streptozotocin, STZ) and normal control groups. Rats in these two groups were further randomly divided into 3, 7, 14, 30, 90 and 180 days-group,including 5 rats respectively. The immunohistochemical studies of ICAM-1, VCAM-1 and CD45 were carried out in the retinal digest preparations or retinal paraffin sections, and the results were analyzed qualitatively, semi-quantitatively.Results: No positive reaction of VCAM-1 was found, and weak reactions of ICAM-1,CD45 were found in nondiabetic rats retina. The difference of 6 control groups had no statistical significance(P ＞ 0.05). The increased ICAM-1 and CD45 staining pattern were detectable 3 days after diabetes induction, and a few VCAM-1 positive cells were observed in the retinal blood capillaries. The difference of diabetes and control is significant( P ＜ 0.05).Following the course, the expressions of ICAM-1, VCAM-1 and CD45 were increasingly enhanced, reaching a peak at the 14th day.Conclusion: Increased expression of ICAM-1, VCAM-1 and leukocytes adhering and stacking in retinal capillaries are the very early events in DR. Coherence of expression and distribution of the three further accounts for it is the key point for the onset of DR that Ams mediates leukocytes adhesion and endothelial cell injury.

Simulated human eye retina adaptive optics imaging system based on a liquid crystal on silicon device

International Nuclear Information System (INIS)

Jiang Baoguang; Cao Zhaoliang; Mu Quanquan; Hu Lifa; Li Chao; Xuan Li

2008-01-01

In order to obtain a clear image of the retina of model eye, an adaptive optics system used to correct the wave-front error is introduced in this paper. The spatial light modulator that we use here is a liquid crystal on a silicon device instead of a conversional deformable mirror. A paper with carbon granule is used to simulate the retina of human eye. The pupil size of the model eye is adjustable (3-7 mm). A Shack–Hartman wave-front sensor is used to detect the wave-front aberration. With this construction, a value of peak-to-valley is achieved to be 0.086 λ, where λ is wavelength. The modulation transfer functions before and after corrections are compared. And the resolution of this system after correction (691p/m) is very close to the dirraction limit resolution. The carbon granule on the white paper which has a size of 4.7 μm is seen clearly. The size of the retina cell is between 4 and 10 mu;m. So this system has an ability to image the human eye's retina. (classical areas of phenomenology)

Functional characterization of rs2229094 (T>C polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

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Pastor-Idoate S

2017-05-01

Full Text Available Salvador Pastor-Idoate,1,2 Irene Rodríguez-Hernández,2,3 Jimena Rojas,1 Lucia Gonzalez-Buendia,1 Santiago Delgado-Tirado,1,4 Jose Carlos López,1 Rogelio González-Sarmiento,2,3 Jose C Pastor1,4 1IOBA Eye Institute, University of Valladolid, Valladolid, 2Molecular Medicine Unit, Department of Medicine, 3Molecular and Cellular Cancer Biology Institute, High Council of Scientific Research, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, 4Department of Ophthalmology, Hospital Clínico Universitario, Valladolid, Spain Purpose: The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R (T>C, previously associated with proliferative vitreoretinopathy (PVR development.Materials and methods: Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD and three healthy control eyes were subjected to immunohistochemistry (IHC with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.Results: RT-PCR analysis revealed no significant levels of messenger RNA (mRNA LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.Conclusion: Although results suggest lack of functionality, the differences found in IHC study and its strong association

Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

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Bianchi, Enrica; Ripandelli, Guido; Taurone, Samanta; Feher, Janos; Plateroti, Rocco; Kovacs, Illes; Magliulo, Giuseppe; Orlando, Maria Patrizia; Micera, Alessandra; Battaglione, Ezio; Artico, Marco

2016-03-01

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes. © The Author(s) 2015.

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

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

2014-02-01

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

Macular pigment carotenoids in the retina and occipital cortex are related in humans

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Objectives: Lutein and zeaxanthin are dietary carotenoids that preferentially accumulate in the macular region of the retina. Together with mesozeaxanthin, a conversion product of lutein in the macula, they form the macular pigment. Lutein is also the predominant carotenoid in human brain tissue and...

ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.

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Rothschild, Pierre-Raphaël; Salah, Sawsen; Berdugo, Marianne; Gélizé, Emmanuelle; Delaunay, Kimberley; Naud, Marie-Christine; Klein, Christophe; Moulin, Alexandre; Savoldelli, Michèle; Bergin, Ciara; Jeanny, Jean-Claude; Jonet, Laurent; Arsenijevic, Yvan; Behar-Cohen, Francine; Crisanti, Patricia

2017-08-18

In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

Histologic correlation of in vivo optical coherence tomography images of the human retina

NARCIS (Netherlands)

Chen, T.; Cense, B.; Miller, J.S.; Rubin, P. A. D.; Deschler, D. G.; Gragoudas, E. S.; de Boer, J.F.

2006-01-01

Purpose: To correlate in vivo human retina optical coherence tomography (OCT)3 images with histology. Design: Case series. Methods: Linear OCT3 scans through the macula and optic nerve were obtained in three eyes of three patients who then underwent exenteration surgery for orbital cancers. OCT3

Resonant imaging of carotenoid pigments in the human retina

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Gellermann, Werner; Emakov, Igor V.; McClane, Robert W.

2002-06-01

We have generated high spatial resolution images showing the distribution of carotenoid macular pigments in the human retina using Raman spectroscopy. A low level of macular pigments is associated with an increased risk of developing age-related macular degeneration, a leading cause of irreversible blindness. Using excised human eyecups and resonant excitation of the pigment molecules with narrow bandwidth blue light from a mercury arc lamp, we record Raman images originating from the carbon-carbon double bond stretch vibrations of lutein and zeaxanthin, the carotenoids comprising human macular pigments. Our Raman images reveal significant differences among subjects, both in regard to absolute levels as well as spatial distribution within the macula. Since the light levels used to obtain these images are well below established safety limits, this technique holds promise for developing a rapid screening diagnostic in large populations at risk for vision loss from age-related macular degeneration.

Connective tissue growth factor is necessary for retinal capillary basal lamina thickening in diabetic mice

NARCIS (Netherlands)

Kuiper, Esther J.; van Zijderveld, Rogier; Roestenberg, Peggy; Lyons, Karen M.; Goldschmeding, Roel; Klaassen, Ingeborg; van Noorden, Cornelis J. F.; Schlingemann, Reinier O.

2008-01-01

Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components. We hypothesize

Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina?

OpenAIRE

Widomska, Justyna; Subczynski, Witold K

2014-01-01

Age-related macular degeneration (AMD) is associated with a low level of macular carotenoids in the eye retina. Only two carotenoids, namely lutein and zeaxanthin are selectively accumulated in the human eye retina from blood plasma where more than twenty other carotenoids are available. The third carotenoid which is found in the human retina, meso-zeaxanthin is formed directly in the retina from lutein. All these carotenoids, named also macular xanthophylls, play key roles in eye health and ...

Diabetic Eye Disease

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... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetic Eye Disease What is diabetic eye disease? Diabetic eye disease is a group ... eye diseases that can threaten your sight are Diabetic retinopathy The retina is the inner lining at ...

Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

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Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

2018-02-14

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

Neurotrophins and Neurotrophin Receptors in Proliferative Diabetic Retinopathy

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Abu El-Asrar, Ahmed M.; Mohammad, Ghulam; De Hertogh, Gert; Nawaz, Mohd Imtiaz; Van Den Eynde, Kathleen; Siddiquei, Mohammad Mairaj; Struyf, Sofie; Opdenakker, Ghislain; Geboes, Karel

2013-01-01

Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR. PMID:23762379

Wavefront optimized nonlinear microscopy of ex vivo human retinas

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Gualda, Emilio J.; Bueno, Juan M.; Artal, Pablo

2010-03-01

A multiphoton microscope incorporating a Hartmann-Shack (HS) wavefront sensor to control the ultrafast laser beam's wavefront aberrations has been developed. This instrument allowed us to investigate the impact of the laser beam aberrations on two-photon autofluorescence imaging of human retinal tissues. We demonstrated that nonlinear microscopy images are improved when laser beam aberrations are minimized by realigning the laser system cavity while wavefront controlling. Nonlinear signals from several human retinal anatomical features have been detected for the first time, without the need of fixation or staining procedures. Beyond the improved image quality, this approach reduces the required excitation power levels, minimizing the side effects of phototoxicity within the imaged sample. In particular, this may be important to study the physiology and function of the healthy and diseased retina.

Diabetic Retinopathy Analysis

Directory of Open Access Journals (Sweden)

R. Sivakumar

2005-01-01

Full Text Available Diabetic retinopathy is one of the common complications of diabetes. Unfortunately, in many cases the patient is not aware of any symptoms until it is too late for effective treatment. Through analysis of evoked potential response of the retina, the optical nerve, and the optical brain center, a way will be paved for early diagnosis of diabetic retinopathy and prognosis during the treatment process. In this paper, we present an artificial-neural-network-based method to classify diabetic retinopathy subjects according to changes in visual evoked potential spectral components and an anatomically realistic computer model of the human eye under normal and retinopathy conditions in a virtual environment using 3D Max Studio and Windows Movie Maker.

Non-mydriatic video ophthalmoscope to measure fast temporal changes of the human retina

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Tornow, Ralf P.; Kolář, Radim; Odstrčilík, Jan

2015-07-01

The analysis of fast temporal changes of the human retina can be used to get insight to normal physiological behavior and to detect pathological deviations. This can be important for the early detection of glaucoma and other eye diseases. We developed a small, lightweight, USB powered video ophthalmoscope that allows taking video sequences of the human retina with at least 25 frames per second without dilating the pupil. Short sequences (about 10 s) of the optic nerve head (20° x 15°) are recorded from subjects and registered offline using two-stage process (phase correlation and Lucas-Kanade approach) to compensate for eye movements. From registered video sequences, different parameters can be calculated. Two applications are described here: measurement of (i) cardiac cycle induced pulsatile reflection changes and (ii) eye movements and fixation pattern. Cardiac cycle induced pulsatile reflection changes are caused by changing blood volume in the retina. Waveform and pulse parameters like amplitude and rise time can be measured in any selected areas within the retinal image. Fixation pattern ΔY(ΔX) can be assessed from eye movements during video acquisition. The eye movements ΔX[t], ΔY[t] are derived from image registration results with high temporal (40 ms) and spatial (1,86 arcmin) resolution. Parameters of pulsatile reflection changes and fixation pattern can be affected in beginning glaucoma and the method described here may support early detection of glaucoma and other eye disease.

What Is Diabetic Retinopathy?

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... Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis Focus On Pediatric Ophthalmology ... Retinopathy Diagnosis Diabetic Retinopathy Treatment Proliferative Diabetic Retinopathy Vision Simulator Non-Proliferative Diabetic ...

Two classes of astrocytes in the adult human and pig retina in terms of their expression of high affinity NGF receptor (TrkA).

Science.gov (United States)

Ruiz-Ederra, Javier; Hitchcock, Peter F; Vecino, Elena

2003-02-13

Astrocytes have been implicated in axon guidance and synaptic regeneration in the retina and these processes involve activation of the high affinity nerve growth factor receptor, known as the tyrosine kinase A (TrkA) receptor. The purpose of the present study was to characterize the expression of TrkA in astrocytes of the adult pig and human retina. To this end, sections of human and pig retinas were immunolabeled with a combination of antibodies to glial fibrillary acidic protein (GFAP) and TrkA. Our study revealed that most of the GFAP-positive cells express TrkA, whereas a rare, novel subpopulation of astrocytes was found to be devoid of TrkA. Our results support the idea that astrocytes play an important neurotrophic role in the retina.

Abnormal Glycogen Storage by Retinal Neurons in Diabetes.

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Gardiner, Tom A; Canning, Paul; Tipping, Nuala; Archer, Desmond B; Stitt, Alan W

2015-12-01

It is widely held that neurons of the central nervous system do not store glycogen and that accumulation of the polysaccharide may cause neurodegeneration. Since primary neural injury occurs in diabetic retinopathy, we examined neuronal glycogen status in the retina of streptozotocin-induced diabetic and control rats. Glycogen was localized in eyes of streptozotocin-induced diabetic and control rats using light microscopic histochemistry and electron microscopy, and correlated with immunohistochemical staining for glycogen phosphorylase and phosphorylated glycogen synthase (pGS). Electron microscopy of 2-month-old diabetic rats (n = 6) showed massive accumulations of glycogen in the perinuclear cytoplasm of many amacrine neurons. In 4-month-old diabetic rats (n = 11), quantification of glycogen-engorged amacrine cells showed a mean of 26 cells/mm of central retina (SD ± 5), compared to 0.5 (SD ± 0.2) in controls (n = 8). Immunohistochemical staining for glycogen phosphorylase revealed strong expression in amacrine and ganglion cells of control retina, and increased staining in cell processes of the inner plexiform layer in diabetic retina. In control retina, the inactive pGS was consistently sequestered within the cell nuclei of all retinal neurons and the retinal pigment epithelium (RPE), but in diabetics nuclear pGS was reduced or lost in all classes of retinal cell except the ganglion cells and cone photoreceptors. The present study identifies a large population of retinal neurons that normally utilize glycogen metabolism but show pathologic storage of the polysaccharide during uncontrolled diabetes.

Balanced steady state free precession for arterial spin labeling MRI: Initial experience for blood flow mapping in human brain, retina, and kidney.

Science.gov (United States)

Park, Sung-Hong; Wang, Danny J J; Duong, Timothy Q

2013-09-01

We implemented pseudo-continuous ASL (pCASL) with 2D and 3D balanced steady state free precession (bSSFP) readout for mapping blood flow in the human brain, retina, and kidney, free of distortion and signal dropout, which are typically observed in the most commonly used echo-planar imaging acquisition. High resolution functional brain imaging in the human visual cortex was feasible with 3D bSSFP pCASL. Blood flow of the human retina could be imaged with pCASL and bSSFP in conjunction with a phase cycling approach to suppress the banding artifacts associated with bSSFP. Furthermore, bSSFP based pCASL enabled us to map renal blood flow within a single breath hold. Control and test-retest experiments suggested that the measured blood flow values in retina and kidney were reliable. Because there is no specific imaging tool for mapping human retina blood flow and the standard contrast agent technique for mapping renal blood flow can cause problems for patients with kidney dysfunction, bSSFP based pCASL may provide a useful tool for the diagnosis of retinal and renal diseases and can complement existing imaging techniques. Copyright © 2013 Elsevier Inc. All rights reserved.

[Effect of internal limiting membrane peeling on morpho-functional state of the retina in patients with proliferative diabetic retinopathy (preliminary report)].

Science.gov (United States)

Bikbov, M M; Fayzrakhmanov, R R; Kalanov, M R

2018-01-01

To compare morpho-functional parameters of retina during vitrectomy with and without internal limiting membrane (ILM) peeling in patients with proliferative diabetic retinopathy. The study included 55 patients (55 eyes) that had underwent vitreoretinal surgery in the setting of antivasoproliferative therapy for proliferative diabetic retinopathy. Patients of the 1 st group (n=27) underwent vitrectomy with silicone tamponade, 2 nd group (n=28) received similar treatment with the addition of ILM peeling. Three months after the treatment, all patients had silicone oil removed. Best Corrected Visual Acuity before treatment was 0.06±0.02 in both groups; after the treatment it improved to 0.1±0.05 (ppeeling during vitrectomy with following silicone oil tamponade eliminates the risk of ERM formation in patients with proliferative diabetic retinopathy in the follow-up period of up to 6-month and results in better morpho-functional parameters in comparison with patients who received similar treatment but without peeling.

Increased intraretinal PO2 in short-term diabetic rats.

Science.gov (United States)

Lau, Jennifer C M; Linsenmeier, Robert A

2014-12-01

In diabetic retinopathy, neovascularization is hypothesized to develop due to hypoxia in the retina. However, evidence for retinal hypoxia is limited, and the progressive changes in oxygenation are unknown. The objective of this study was to determine if retinal hypoxia occurs early in the development of diabetes. Intraretinal oxygen (PO2) profiles were recorded with oxygen-sensitive microelectrodes in control and diabetic Long-Evans rats at 4 and 12 weeks after induction of diabetes. Diabetes did not affect oxygen consumption in the photoreceptors in either dark or light adaptation. Oxygenation of the inner retina was not affected after 4 weeks of diabetes, although vascular endothelial growth factor levels increased. At 12 weeks, average inner retinal PO2, normalized to choriocapillaris PO2, was higher in diabetic rats than in age-matched controls, which was opposite to what was expected. Thus retinal hypoxia is not a condition of early diabetes in rat retina. Increased inner retinal PO2 may occur because oxygen consumption decreases in the inner retina. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry.

Science.gov (United States)

Zemski Berry, Karin A; Gordon, William C; Murphy, Robert C; Bazan, Nicolas G

2014-03-01

MALDI imaging mass spectrometry (IMS) was used to characterize lipid species within sections of human eyes. Common phospholipids that are abundant in most tissues were not highly localized and observed throughout the accessory tissue, optic nerve, and retina. Triacylglycerols were highly localized in accessory tissue, whereas sulfatide and plasmalogen glycerophosphoethanolamine (PE) lipids with a monounsaturated fatty acid were found enriched in the optic nerve. Additionally, several lipids were associated solely with the inner retina, photoreceptors, or retinal pigment epithelium (RPE); a plasmalogen PE lipid containing DHA (22:6), PE(P-18:0/22:6), was present exclusively in the inner retina, and DHA-containing glycerophosphatidylcholine (PC) and PE lipids were found solely in photoreceptors. PC lipids containing very long chain (VLC)-PUFAs were detected in photoreceptors despite their low abundance in the retina. Ceramide lipids and the bis-retinoid, N-retinylidene-N-retinylethanolamine, was tentatively identified and found only in the RPE. This MALDI IMS study readily revealed the location of many lipids that have been associated with degenerative retinal diseases. Complex lipid localization within retinal tissue provides a global view of lipid organization and initial evidence for specific functions in localized regions, offering opportunities to assess their significance in retinal diseases, such as macular degeneration, where lipids have been implicated in the disease process.

Non-Proliferative Diabetic Retinopathy Vision Simulator

Science.gov (United States)

... Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis Focus On Pediatric Ophthalmology ... Retinopathy Diagnosis Diabetic Retinopathy Treatment Proliferative Diabetic Retinopathy Vision Simulator Non-Proliferative Diabetic ...

Diabetic Eye Problems

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... damage your eyes. The most common problem is diabetic retinopathy. It is a leading cause of blindness ... You need a healthy retina to see clearly. Diabetic retinopathy damages the tiny blood vessels inside your ...

EVALUATION OF INHOMOGENEITIES IN HISTOLOGICAL STRUCTURES (CARTILAGE, RETINA

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Lutz Muche

2011-05-01

Full Text Available This paper investigates histological tissues by means of image analysis and spatial statistics. For the quantification of cell frequencies and accumulations two statistical characteristics, intensity function and cluster density, are suggested. The samples are histological sections of human articular cartilage and human retina considered in view of changes during the ageing process. The articular cartilage is characterized by continuous changes of both functions, the cell intensity as well as the clusterization. In contrast, the retina is a trilaminar structure formed in the early embryonic stage without changes by ageing.

Characterization of Retinal Vascular and Neural Damage in a Novel Model of Diabetic Retinopathy.

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Weerasekera, Lakshini Y; Balmer, Lois A; Ram, Ramesh; Morahan, Grant

2015-06-01

Diabetic retinopathy (DR) is a major cause of blindness globally. Investigating the underlying mechanisms of DR would be aided by a suitable mouse model that developed key features seen in the human disease, and did so without carrying genetic modifications. This study was undertaken to produce such a model. Our panel of Collaborative Cross strains was screened for DR-like features after induction of diabetes by intravenous injection with alloxan or streptozotocin. Both flat-mounted whole-retina and histologic sections were studied for the presence of retinal lesions. Progression of DR was also studied by histologic examination of the retinal vascular and neural structure at various time points after diabetes onset. In addition, microarray investigations were conducted on retinas from control and diabetic mice. Features of DR such as degenerated pericytes, acellular capillaries, minor vascular proliferation, gliosis of Müller cells, and loss of ganglion cells were noted as early as day 7 in some mice. These lesions became more evident with time. After 21 days of diabetes, severe vascular proliferation, microaneurysms, preretinal damage, increased Müller cell gliosis, and damage to the outer retina were all obvious. Microarray studies found significant differential expression of multiple genes known to be involved in DR. The FOT_FB strain provides a useful model to investigate the pathogenesis of DR and to develop treatments for this vision-threatening disease.

Detection of Elevated Signaling Amino Acids in Human Diabetic Vitreous by Rapid Capillary Electrophoresis

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Miao-Jen Lu

2007-01-01

Full Text Available Elevated glutamate is implicated in the pathology of PDR. The ability to rapidly assess the glutamate and amino acid content of vitreous provides a more complete picture of the chemical changes occurring at the diabetic retina and may lead to a better understanding of the pathology of PDR. Vitreous humor was collected following vitrectomies of patients with PDR and control conditions of macular hole or epiretinal membrane. A capillary electrophoresis method was developed to quantify glutamate and arginine. The analysis is relatively fast (<6 minutes and utilizes a poly(ethyleneoxide and sodium dodecylsulfate run buffer. Both amino acid levels show significant increases in PDR patients versus controls and are comparable to other reports. The levels of vitreal glutamate vary inversely with the degree of observed hemorrhage. The results demonstrate a rapid method for assessment of a number of amino acids to characterize the chemical changes at the diabetic retina to better understand tissue changes and potentially identify new treatments.

Photophysical properties of xanthophylls in carotenoproteins from human retinas.

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Billsten, Helena H; Bhosale, Prakash; Yemelyanov, Alexander; Bernstein, Paul S; Polívka, Tomás

2003-08-01

The macula of the human retina contains high amounts of the xanthophyll carotenoids lutein and zeaxanthin [a mixture of (3R,3'R)-zeaxanthin and (3R,3'S-meso)-zeaxanthin]. Recently, it was shown that the uptake and the stabilization of zeaxanthin and lutein into the retina are likely to be mediated by specific xanthophyll-binding proteins (XBP). Here, we have used femtosecond pump-probe spectroscopy to study the dynamics of the S1 state of these xanthophylls in xanthophyll-enriched and native XBP. The results from the native XBP and the enriched XBP were then compared with those for carotenoids in organic solvents and in detergent micelles. Steady-state and transient absorption spectra show that the incorporation of xanthophylls into the protein causes a redshift of the spectra, which is stronger for lutein than for zeaxanthin. The transient absorption spectra further indicate that a part of the xanthophylls remains unbound in the xanthophyll-enriched XBP. The transient absorption spectra of the native XBP prove the presence of both xanthophylls in native XBP. Although the S1 lifetime of lutein does not exhibit any changes when measured in solution, micelles or XBP, we have observed the influence of the environment on the S1 lifetime of meso-zeaxanthin, which has a longer (12 ps) lifetime in XBP than in solution (9 ps). The most pronounced effect was found for vibrational relaxation in the S1 state, which is significantly slower for xanthophylls in XBP compared with micelles and solution. This effect is more pronounced for meso-zeaxanthin, suggesting a specific site of binding of this carotenoid to XBP.

The infrared retina

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Krishna, Sanjay

2009-01-01

As infrared imaging systems have evolved from the first generation of linear devices to the second generation of small format staring arrays to the present 'third-gen' systems, there is an increased emphasis on large area focal plane arrays (FPAs) with multicolour operation and higher operating temperature. In this paper, we discuss how one needs to develop an increased functionality at the pixel level for these next generation FPAs. This functionality could manifest itself as spectral, polarization, phase or dynamic range signatures that could extract more information from a given scene. This leads to the concept of an infrared retina, which is an array that works similarly to the human eye that has a 'single' FPA but multiple cones, which are photoreceptor cells in the retina of the eye that enable the perception of colour. These cones are then coupled with powerful signal processing techniques that allow us to process colour information from a scene, even with a limited basis of colour cones. Unlike present day multi or hyperspectral systems, which are bulky and expensive, the idea would be to build a poor man's 'infrared colour' camera. We use examples such as plasmonic tailoring of the resonance or bias dependent dynamic tuning based on quantum confined Stark effect or incorporation of avalanche gain to achieve embodiments of the infrared retina.

Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment

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Abcouwer, Steven F.; Gardner, Thomas W.

2014-01-01

Diabetic retinopathy (DR) impairs vision of patients with type 1 and type 2 diabetes, associated with vascular dysfunction and occlusion, retinal edema, hemorrhage, and inappropriate growth of new blood vessels. The recent success of biologic treatments targeting vascular endothelial growth factor (VEGF) demonstrates that treating the vascular aspects in the later stages of the disease can preserve vision in many patients. It would also be highly desirable to prevent the onset of the disease or arrest its progression at a stage preceding the appearance of overt microvascular pathologies. The progression of DR is not necessarily linear but may follow a series of steps that evolve over the course of multiple years. Abundant data suggest that diabetes affects the entire neurovascular unit of the retina, with an early loss of neurovascular coupling, gradual neurodegeneration, gliosis, and neuroinflammation before observable vascular pathologies. In this article, we consider the pathology of diabetic retinopathy from the point of view that diabetes causes measurable dysfunctions in the complex integral network of cell types that produce and maintain human vision. PMID:24673341

Intravitreal Injection of Ranibizumab and CTGF shRNA Improves Retinal Gene Expression and Microvessel Ultrastructure in a Rodent Model of Diabetes

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Bojie Hu

2014-01-01

Full Text Available Therapeutic modalities targeting vascular endothelial growth factor (VEGF have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy.

Inflammation in Diabetic Retinopathy

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Tang, Johnny; Kern, Timothy S.

2012-01-01

Diabetes causes a number of metabolic and physiologic abnormalities in the retina, but which of these abnormalities contribute to recognized features of diabetic retinopathy (DR) is less clear. Many of the molecular and physiologic abnormalities that have been found to develop in the retina in diabetes are consistent with inflammation. Moreover, a number of anti-inflammatory therapies have been found to significantly inhibit development of different aspects of DR in animal models. Herein, we review the inflammatory mediators and their relationship to early and late DR, and discuss the potential of anti-inflammatory approaches to inhibit development of different stages of the retinopathy. We focus primarily on information derived from in vivo studies, supplementing with information from in vitro studies were important. PMID:21635964

Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.

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Wang, Wenjun; Wang, Qing; Wan, Danyang; Sun, Yue; Wang, Lin; Chen, Hong; Liu, Chengyu; Petersen, Robert B; Li, Jianshuang; Xue, Weili; Zheng, Ling; Huang, Kun

2017-05-04

Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.

Human bone marrow mesenchymal stem cells for retinal vascular injury.

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

2017-09-01

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

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

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

2002-01-01

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

Neurodegeneration and Neuroprotection in Diabetic Retinopathy

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Abdullah S. Alhomida

2013-01-01

Full Text Available Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide.

Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism.

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Mahmoud, Ayman M; Abd El-Twab, Sanaa M; Abdel-Reheim, Eman S

2017-06-01

Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated. Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks. Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina. These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.

A digital retina-like low-level vision processor.

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Mertoguno, S; Bourbakis, N G

2003-01-01

This correspondence presents the basic design and the simulation of a low level multilayer vision processor that emulates to some degree the functional behavior of a human retina. This retina-like multilayer processor is the lower part of an autonomous self-organized vision system, called Kydon, that could be used on visually impaired people with a damaged visual cerebral cortex. The Kydon vision system, however, is not presented in this paper. The retina-like processor consists of four major layers, where each of them is an array processor based on hexagonal, autonomous processing elements that perform a certain set of low level vision tasks, such as smoothing and light adaptation, edge detection, segmentation, line recognition and region-graph generation. At each layer, the array processor is a 2D array of k/spl times/m hexagonal identical autonomous cells that simultaneously execute certain low level vision tasks. Thus, the hardware design and the simulation at the transistor level of the processing elements (PEs) of the retina-like processor and its simulated functionality with illustrative examples are provided in this paper.

Protective effect of pomegranate juice on retinal oxidative stress in streptozotocin-induced diabetic rats

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Betul Tugcu

2017-11-01

Full Text Available AIM: To investigate the effect of pomegranate juice (PJ intake on overall oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were divided into four groups as control (CO, diabetic (DM, control treated with PJ (CO-PJ, and diabetic treated with PJ (DM-PJ.The retina tissues were used to determine 8-hydroxy-2’-deoxyguanosine (8OHdG, malondialdehyde (MDA, reduced glutathione (GSH levels, and the enzyme activities of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px. RESULTS: The levels of 8OHdG and MDA were significantly increased in the retina of DM group compared to CO group (P=0.001, P<0.001 respectively. Both 8OHdG and MDA levels were decreased in PJ-DM group compared to DM group (P=0.004, P<0.001 respectively. The activities of antioxidant enzymes GSH, SOD, and GDH-Px were significantly decreased in the retina of DM group compared to CO group (P≤0.01. GSH and GSH-Px activities were higher in PJ-DM group compared with DM group (P=0.010, P=0.042, respectively but SOD activity was not statistically different (P=0.938. CONCLUSION: PJ intake is found to be effective in decreasing oxidative end products, and in increasing the activities of antioxidant enzymes in diabetic retinas of rats, which suggests it may be effective against oxidative stress in diabetic retinas.

Retina Image Analysis and Ocular Telehealth: The Oak Ridge National Laboratory-Hamilton Eye Institute Case Study

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Karnowski, Thomas Paul [ORNL; Giancardo, Luca [ORNL; Li, Yaquin [University of Tennessee, Knoxville (UTK); Tobin Jr, Kenneth William [ORNL; Chaum, Edward [University of Tennessee, Knoxville (UTK)

2013-01-01

Automated retina image analysis has reached a high level of maturity in recent years, and thus the question of how validation is performed in these systems is beginning to grow in importance. One application of retina image analysis is in telemedicine, where an automated system could enable the automated detection of diabetic retinopathy and other eye diseases as a low-cost method for broad-based screening. In this work we discuss our experiences in developing a telemedical network for retina image analysis, including our progression from a manual diagnosis network to a more fully automated one. We pay special attention to how validations of our algorithm steps are performed, both using data from the telemedicine network and other public databases.

Current knowledge on diabetic retinopathy from humandonor tissues

Institute of Scientific and Technical Information of China (English)

Jessica H Eisma; Jennifer E Dulle; Patrice E Fort

2015-01-01

According to the American Diabetes Association, diabetes was the seventh leading cause of death, and diabetic retinopathy the leading cause of blindness in working age adults in the United States in 2010. Diabetes is characterized by hyperglycemia associated with either hypoinsulinemia or insulin resistance, and over time, this chronic metabolic condition may lead to various complications including kidney failure, heart attacks,and retinal degeneration. In order to better understandthe molecular basis of this disease and its complications,animal models have been the primary approach usedto investigate the effects of diabetes on various tissuesor cell types of the body, including the retina. However,inherent to these animal models are critical limitationsthat make the insight gained from these modelschallenging to apply to the human pathology. Thesedifficulties in translating the knowledge obtained fromanimal studies have led a growing number of researchgroups to explore the diabetes complications, especiallydiabetic retinopathy, on tissues from human donors.This review summarizes the data collected from diabeticpatients at various stages of diabetic retinopathy andclassifies the data based upon their relevance to themain aspects of diabetic retinopathy： retinal vasculaturedysfunction, inflammation, and neurodegeneration. Thisreview discusses the importance of those studies todiscriminate and establish the relevance of the findingsobtained from animal models but also the limitations ofsuch approaches.

An experimental platform for systemic drug delivery to the retina.

LENUS (Irish Health Repository)

Campbell, Matthew

2009-10-20

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

Desprendimiento de retina

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L. Jaime Claramunt, Dr.

2010-01-01

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

Desprendimiento de retina

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L. Jaime Claramunt, Dr.

2010-11-01

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

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a potential biomarker of angiogenesis in proliferative diabetic retinopathy.

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Abu El-Asrar, Ahmed M; Ahmad, Ajmal; Alam, Kaiser; Siddiquei, Mohammad Mairaj; Mohammad, Ghulam; Hertogh, Gert De; Mousa, Ahmed; Opdenakker, Ghislain

2017-11-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) promotes angiogenesis through matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) production. We investigated the expression levels of EMMPRIN and correlated these levels with VEGF, MMP-1 and MMP-9 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of EMMPRIN in the retinas of diabetic rats and the effect of EMMPRIN on the induction of angiogenesis regulatory factors in human retinal microvascular endothelial cells (HRMECs). Vitreous samples from 40 PDR and 19 non-diabetic patients, epiretinal membranes from 12 patients with PDR, retinas of rats and HRMECs were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, Western blot analysis, zymography analysis and RT-PCR. We showed a significant increase in the expression of EMMPRIN, VEGF, MMP-1 and MMP-9 in vitreous samples from PDR patients compared with non-diabetic controls (p EMMPRIN and the levels of VEGF (r = 0.38; p = 0.003), MMP-1 (r = 0.36; p = 0.005) and MMP-9 (r = 0.46; p = 0.003). In epiretinal membranes, EMMPRIN was expressed in vascular endothelial cells and stromal cells. Significant increase of EMMPRIN mRNA was detected in rat retinas after induction of diabetes. EMMPRIN induced hypoxia-inducible factor-1α, VEGF and MMP-1 expression in HRMEC. These results suggest that EMMPRIN/MMPs/VEGF pathway is involved in PDR angiogenesis. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

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匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

2003-01-01

Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P＜0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

Connecting the Retina to the Brain

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Lynda Erskine

2014-12-01

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

The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration

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Altmann, Christine

2018-01-01

Diabetic retinopathy is a common complication of diabetes mellitus, which appears in one third of all diabetic patients and is a prominent cause of vision loss. First discovered as a microvascular disease, intensive research in the field identified inflammation and neurodegeneration to be part of diabetic retinopathy. Microglia, the resident monocytes of the retina, are activated due to a complex interplay between the different cell types of the retina and diverse pathological pathways. The trigger for developing diabetic retinopathy is diabetes-induced hyperglycemia, accompanied by leukostasis and vascular leakages. Transcriptional changes in activated microglia, mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and extracellular signal–regulated kinase (ERK) signaling pathways, results in release of various pro-inflammatory mediators, including cytokines, chemokines, caspases and glutamate. Activated microglia additionally increased proliferation and migration. Among other consequences, these changes in microglia severely affected retinal neurons, causing increased apoptosis and subsequent thinning of the nerve fiber layer, resulting in visual loss. New potential therapeutics need to interfere with these diabetic complications even before changes in the retina are diagnosed, to prevent neuronal apoptosis and blindness in patients. PMID:29301251

Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

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Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos

2013-01-01

Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.

Insulin-like activity in the retina

International Nuclear Information System (INIS)

Das, A.

1986-01-01

A number of studies have recently demonstrated that insulin or a homologous peptide may be synthesized outside the pancreas also. The present study was designed to investigate whether insulin-like activity exists in the retina, and if it exists, whether it is due to local synthesis of insulin or a similar peptide in the retina. To determine whether the insulin-like immunoreactivity in retinal glial cells is due to binding and uptake or local synthesis of insulin, a combined approach of immunocytochemistry and in situ DNA-RNA hybridization techniques was used on cultured rat retinal glial cells. Insulin-like immunoreactivity was demonstrated in the cytoplasma of these cells. In situ hybridization studies using labeled rat insulin cDNA indicated that these cells contain the mRNA necessary for de novo synthesis of insulin or a closely homologous peptide. Since human retinal cells have, as yet, not been conveniently grown in culture, an ocular tumor cell line, human Y79 retinoblastoma was used as a model to extend these investigations. The presence of insulin-like immunoreactivity as well as insulin-specific mRNA was demonstrated in this cell line. Light microscopic autoradiography following incubation of isolated rat retinal cells with 125 I-insulin showed the presence of insulin binding sites on the photoreceptors and amarcine cells. On the basis of these observations that rat retina glial cells, including Muller cells are sites of synthesis of insulin or a similar peptide, a model for the pathogenesis of dabetic retinopathy is proposed

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

Science.gov (United States)

Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

Protective effect of pomegranate juice on retinal oxidative stress in streptozotocin-induced diabetic rats

OpenAIRE

Betul Tugcu; Senay Asik Nacaroglu; Asuman Gedikbasi; Mehmet Uhri; Nur Acar; Hakan Ozdemir

2017-01-01

AIM: To investigate the effect of pomegranate juice (PJ) intake on overall oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were divided into four groups as control (CO), diabetic (DM), control treated with PJ (CO-PJ), and diabetic treated with PJ (DM-PJ).The retina tissues were used to determine 8-hydroxy-2’-deoxyguanosine (8OHdG), malondialdehyde (MDA), reduced glutathione (GSH) levels, and the enzyme activities of superoxide dismutase (SOD) and glutathione peroxi...

Optimal wavelet transform for the detection of microaneurysms in retina photographs

OpenAIRE

Quellec, Gwénolé; Lamard, Mathieu; Josselin, Pierre Marie; Cazuguel, Guy; Cochener, Béatrice; Roux, Christian

2008-01-01

11 pages; International audience; In this paper, we propose an automatic method to detect microaneurysms in retina photographs. Microaneurysms are the most frequent and usually the first lesions to appear as a consequence of diabetic retinopathy. So, their detection is necessary for both screening the pathology and follow up (progression measurement). Automating this task, which is currently performed manually, would bring more objectivity and reproducibility. We propose to detect them by loc...

Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

Science.gov (United States)

Widomska, Justyna; Zareba, Mariusz; Subczynski, Witold Karol

2016-01-01

Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases. PMID:27030822

Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

Directory of Open Access Journals (Sweden)

Justyna Widomska

2016-01-01

Full Text Available Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin. Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls, are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases.

Localization and characterization of immunocompetent cells in the human retina

NARCIS (Netherlands)

Yang, P.; Das, P. K.; Kijlstra, A.

2000-01-01

Recent studies have shown that experimental uveitis can be induced by the appropriate administration of various retinal antigens. Little is known about the in-situ interactions between immune cells in the retina as a prerequisite for understanding the mechanisms involving the presentation of

Protective effects of a coumarin derivative in diabetic rats.

Science.gov (United States)

Bucolo, Claudio; Ward, Keith W; Mazzon, Emanuela; Cuzzocrea, Salvatore; Drago, Filippo

2009-08-01

Retinal microvascular cells play a crucial role in the pathogenesis of diabetic retinopathy. The endothelial effects of cloricromene, a novel coumarin derivative, on diabetic retinopathy induced by streptozotocin (STZ) in the rat were investigated. Cloricromene (10 mg/kg intraperitoneally) was administered daily in diabetic rats, and 60 days later eyes were enucleated for localization of nitrotyrosine, ICAM-1, VEGF, ZO-1, occludin, claudin-5, and VE-cadherin by immunohistochemical analysis. The effect of treatment was also evaluated by TNFalpha, ICAM-1, VEGF, and eNOS protein levels measurement in the retina with the respective ELISA kits. Blood-retinal barrier (BRB) integrity was also evaluated by Evans blue. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina. Cloricromene treatment significantly lowered retinal TNFalpha, ICAM-1, VEGF, and eNOS. Furthermore, immunohistochemical analysis for VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions revealed positive staining in the retina from STZ-treated rats. The degree of staining for VEGF, ICAM-1, nitrotyrosine, and tight junctions was markedly reduced in tissue sections obtained from diabetic rats treated with cloricromene. Treatment with cloricromene suppressed diabetes-related BRB breakdown by 45%. This study provides the first evidence that the new coumarin derivative cloricromene attenuates the degree of inflammation preserving the BRB in diabetic rats.

Effect of carbamylated erythropoietin on retinopathy of diabetic rats

Institute of Scientific and Technical Information of China (English)

Lin Jiang

2017-01-01

Objective:To study the effect of carbamylated erythropoietin (CEPO) on retinopathy of diabetic rats.Methods: Male SD rats were selected as experimental animals and randomly divided into control group, DM group and CEPO group, and diabetic animal models were established and then given CEPO intervention. 2 weeks after intervention, the retina was collected to detect the expression of angiogenesis molecules, apoptosis molecules and oxidative stress pathway molecules.Results: HIF-1α, VEGF, Ang-1, Bax, Caspase-3, Nrf-2, ARE, HO-1 and NQO-1 mRNA expression in retina of DM group were significantly higher than those of control group while TKLK, PEDF, Bcl-2 and Survivin mRNA expression were significantly lower than those of control group; HIF-1α, VEGF, Ang-1, TKLK and PEDF mRNA expression in retina of CEPO group were not significantly different from those of DM group, Bcl-2, Survivin, Nrf-2, ARE, HO-1 and NQO-1 mRNA expression were significantly higher than those of DM group, and Bax and Caspase-3 mRNA expression were significantly lower than those of DM group.Conclusion:CEPO can reduce the apoptosis and oxidative stress injury of the retina tissue in diabetic rats without affecting the angiogenesis.

CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development.

Directory of Open Access Journals (Sweden)

Scott F Geller

2009-08-01

Full Text Available Mutations in the CLRN1 gene cause Usher syndrome type 3 (USH3, a human disease characterized by progressive blindness and deafness. Clarin 1, the protein product of CLRN1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and recently demonstrated to be associated with the cytoskeleton. To study Clrn1, we created a Clrn1 knockout (KO mouse and characterized the histological and functional consequences of Clrn1 deletion in the retina and cochlea. Clrn1 KO mice do not develop a retinal degeneration phenotype, but exhibit progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized by 4 months, and some Clrn1 KO mice exhibited circling behavior by 5-6 months of age. Clrn1 mRNA expression was localized in the retina using in situ hybridization (ISH, laser capture microdissection (LCM, and RT-PCR. Retinal Clrn1 transcripts were found throughout development and adulthood by RT-PCR, although expression peaked at P7 and declined to undetectable levels in adult retina by ISH. LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas. Examination of Clrn1 KO mice suggests that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function. This may reflect a redundancy in the mouse retina not present in human retina. In contrast to mouse KO models of USH1 and USH2, our data indicate that Clrn1 expression in the retina is restricted to the Müller glia. This is a novel finding, as most retinal degeneration associated proteins are expressed in photoreceptors, not in glia. If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal

Characterisation of human non-proliferativediabetic retinopathy using the fractal analysis

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Carmen Alina Lupaşcu

2015-08-01

Full Text Available AIM:To investigate and quantify changes in the branching patterns of the retina vascular network in diabetes using the fractal analysis method.METHODS:This was a clinic-based prospective study of 172 participants managed at the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and December 2013. A set of 172 segmented and skeletonized human retinal images, corresponding to both normal (24 images and pathological (148 images states of the retina were examined. An automatic unsupervised method for retinal vessel segmentation was applied before fractal analysis. The fractal analyses of the retinal digital images were performed using the fractal analysis software ImageJ. Statistical analyses were performed for these groups using Microsoft Office Excel 2003 and GraphPad InStat software.RESULTS:It was found that subtle changes in the vascular network geometry of the human retina are influenced by diabetic retinopathy (DR and can be estimated using the fractal geometry. The average of fractal dimensions D for the normal images (segmented and skeletonized versions is slightly lower than the corresponding values of mild non-proliferative DR (NPDR images (segmented and skeletonized versions. The average of fractal dimensions D for the normal images (segmented and skeletonized versions is higher than the corresponding values of moderate NPDR images (segmented and skeletonized versions. The lowest values were found for the corresponding values of severe NPDR images (segmented and skeletonized versions.CONCLUSION:The fractal analysis of fundus photographs may be used for a more complete undeTrstanding of the early and basic pathophysiological mechanisms of diabetes. The architecture of the retinal microvasculature in diabetes can be quantitative quantified by means of the fractal dimension. Microvascular abnormalities on retinal imaging may elucidate early mechanistic pathways for microvascular complications and distinguish patients with

Diabetic retinopathy

DEFF Research Database (Denmark)

Wong, Tien Y; Cheung, Chui Ming Gemmy; Larsen, Michael

2016-01-01

Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is a major cause of vision loss in middle-aged and elderly people. One-third of people with diabetes have DR. Severe stages of DR include proliferative DR, caused by the abnormal growth of new retinal blood vessels......, and diabetic macular oedema, in which there is exudation and oedema in the central part of the retina. DR is strongly associated with a prolonged duration of diabetes, hyperglycaemia and hypertension. It is traditionally regarded as a microvascular disease, but retinal neurodegeneration is also involved...... (VEGF). Optimal control of blood glucose and blood pressure in individuals with diabetes remains the cornerstone for preventing the development and arresting the progression of DR. Anti-VEGF therapy is currently indicated for diabetic macular oedema associated with vision loss, whereas laser...

A programmable artificial retina

International Nuclear Information System (INIS)

Bernard, T.M.; Zavidovique, B.Y.; Devos, F.J.

1993-01-01

An artificial retina is a device that intimately associates an imager with processing facilities on a monolithic circuit. Yet, except for simple environments and applications, analog hardware will not suffice to process and compact the raw image flow from the photosensitive array. To solve this output problem, an on-chip array of bare Boolean processors with halftoning facilities might be used, providing versatility from programmability. By setting the pixel memory size to 3 b, the authors have demonstrated both the technological practicality and the computational efficiency of this programmable Boolean retina concept. Using semi-static shifting structures together with some interaction circuitry, a minimal retina Boolean processor can be built with less than 30 transistors and controlled by as few as 6 global clock signals. The successful design, integration, and test of such a 65x76 Boolean retina on a 50-mm 2 CMOS 2-μm circuit are presented

Advances in retinal imaging for diabetic retinopathy and diabetic macular edema.

Science.gov (United States)

Tan, Colin Siang Hui; Chew, Milton Cher Yong; Lim, Louis Wei Yi; Sadda, Srinivas R

2016-01-01

Diabetic retinopathy and diabetic macular edema (DME) are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA) detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT) provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease.

Advances in retinal imaging for diabetic retinopathy and diabetic macular edema

Directory of Open Access Journals (Sweden)

Colin Siang Hui Tan

2016-01-01

Full Text Available Diabetic retinopathy and diabetic macular edema (DME are leading causes of blindness throughout the world, and cause significant visual morbidity. Ocular imaging has played a significant role in the management of diabetic eye disease, and the advent of advanced imaging modalities will be of great value as our understanding of diabetic eye diseases increase, and the management options become increasingly varied and complex. Color fundus photography has established roles in screening for diabetic eye disease, early detection of progression, and monitoring of treatment response. Fluorescein angiography (FA detects areas of capillary nonperfusion, as well as leakage from both microaneurysms and neovascularization. Recent advances in retinal imaging modalities complement traditional fundus photography and provide invaluable new information for clinicians. Ultra-widefield imaging, which can be used to produce both color fundus photographs and FAs, now allows unprecedented views of the posterior pole. The pathologies that are detected in the periphery of the retina have the potential to change the grading of disease severity, and may be of prognostic significance to disease progression. Studies have shown that peripheral ischemia may be related to the presence and severity of DME. Optical coherence tomography (OCT provides structural detail of the retina, and the quantitative and qualitative features are useful in the monitoring of diabetic eye disease. A relatively recent innovation, OCT angiography, produces images of the fine blood vessels at the macula and optic disc, without the need for contrast agents. This paper will review the roles of each of these imaging modalities for diabetic eye disease.

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

Science.gov (United States)

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

2004-12-01

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

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.

Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina.

Science.gov (United States)

Mollick, Tanzina; Mohlin, Camilla; Johansson, Kjell

2016-09-01

Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Müller cell gliosis only seemed to be alleviated in terms of reduced Müller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Müller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the Treatment of Diabetic Retinopathy A Research Project

Science.gov (United States)

Kupfer, Carl

1973-01-01

Evaluated is the treatment of diabetic retinopathy (blindness due to ruptured vessels of the retina as a side effect of diabetes), and described is a research project comparing two types of photocoagulation treatment. (DB)

Diurnal rodents as animal models of human central vision: characterisation of the retina of the sand rat Psammomys obsesus.

Science.gov (United States)

Saïdi, Tounès; Mbarek, Sihem; Chaouacha-Chekir, Rafika Ben; Hicks, David

2011-07-01

Cone photoreceptor-based central vision is of paramount importance in human eyesight, and the increasing numbers of persons affected by macular degeneration emphasizes the need for relevant and amenable animal models. Although laboratory mice and rats have provided valuable information on retinal diseases, they have inherent limitations for studies on macular pathology. In the present study, we extend our recent analyses of diurnal murid rodents to demonstrate that the sand rat Psammomys obesus has a remarkably cone-rich retina, and represents a useful adjunct to available animal models of central vision. Adult P. obesus were captured and transferred to animal facilities where they were maintained under standard light/dark cycles. Animals were euthanised and their eyes enucleated. Tissue was either fixed in paraformaldehyde and prepared for immunohistochemistry, or solubilized in lysis buffer and separated by SDS-PAGE and subjected to western blot analysis. Samples were labelled with a battery of antibodies against rod and cone photoreceptors, inner retinal neurones, and glia. P. obesus showed a high percentage of cones, 41% of total photoreceptor numbers in both central and peripheral retina. They expressed multiple cone-specific proteins, including short and medium-wavelength opsin and cone transducin. A second remarkable feature of the retina concerned the horizontal cells, which expressed high levels of glial fibrillar acidic protein and occludin, two proteins which are not seen in other species. The retina of P. obesus displays high numbers of morphologically and immunologically identifiable cones which will facilitate analysis of cone pathophysiology in this species. The unusual horizontal cell phenotype may be related to the cone distribution or to an alternative facet of the animals lifestyle.

A Role for Excitatory Amino Acids in Diabetic Eye Disease

Directory of Open Access Journals (Sweden)

Jose E. Pulido

2007-01-01

Full Text Available Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina.

Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice.

Science.gov (United States)

Saliba, Alexandra; Du, Yunpeng; Liu, Haitao; Patel, Shyam; Roberts, Robin; Berkowitz, Bruce A; Kern, Timothy S

2015-01-01

Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in retinas of albino rats. Here, we test the hypothesis that photobiomodulation (PBM) is effective in diabetic, pigmented mice, even when delayed until weeks after onset of diabetes. Direct and indirect effects of PBM on the retina also were studied. Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm) daily. In one study, mice were diabetic for 4 weeks before initiation of PBM for an additional 10 weeks. Retinal oxidative stress, inflammation, and retinal function were measured. In some mice, heads were covered with a lead shield during PBM to prevent direct illumination of the eye, or animals were treated with an inhibitor of heme oxygenase-1. In a second study, PBM was initiated immediately after onset of diabetes, and administered daily for 2 months. These mice were examined using manganese-enhanced MRI to assess effects of PBM on transretinal calcium channel function in vivo. PBM intervention improved diabetes-induced changes in superoxide generation, leukostasis, expression of ICAM-1, and visual performance. PBM acted in part remotely from the retina because the beneficial effects were achieved even with the head shielded from the light therapy, and because leukocyte-mediated cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers. PBM induces retinal protection against abnormalities induced by diabetes in pigmented animals, and even as an intervention. Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms. PBM is a novel non-pharmacologic treatment strategy to inhibit early changes of diabetic retinopathy.

Distribution of light in the human retina under natural viewing conditions

Science.gov (United States)

Gibert, Jorge C.

Age-related macular degeneration (AMD) is the leading cause of blindness inAmerica. The fact that AMD wreaks most of the damage in the center of the retina raises the question of whether light, integrated over long periods, is more concentrated in the macula. A method, based on eye-tracking, was developed to measure the distribution of light in the retina under natural viewing conditions. The hypothesis was that integrated over time, retinal illumination peaked in the macula. Additionally a possible relationship between age and retinal illumination was investigated. The eye tracker superimposed the subject's gaze position on a video recorded by a scene camera. Five informed subjects were employed in feasibility tests, and 58 naive subjects participated in 5 phases. In phase 1 the subjects viewed a gray-scale image. In phase 2, they observed a sequence of photographic images. In phase 3 they viewed a video. In phase 4, they worked on a computer; in phase 5, the subjects walked around freely. The informed subjects were instructed to gaze at bright objects in the field of view and then at dark objects. Naive subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, and the video provided by the scene camera, the cumulative light distribution on the retina was calculated for ˜15° around the fovea. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark objects respectively. The light distribution maps obtained from the naive subjects presented a tendency to peak in the macula for phases 1, 2, and 3, a consistent tendency in phase 4 and a variable tendency in phase 5. The feasibility of using an eye-tracker system to measure the distribution of light in the retina was demonstrated, thus helping to understand the role played by light exposure in the etiology of AMD. Results showed that a tendency for light to peak in the macula is a characteristic of some

Adaptive Optical System for Retina Imaging Approaches Clinic Applications

Science.gov (United States)

Ling, N.; Zhang, Y.; Rao, X.; Wang, C.; Hu, Y.; Jiang, W.; Jiang, C.

We presented "A small adaptive optical system on table for human retinal imaging" at the 3rd Workshop on Adaptive Optics for Industry and Medicine. In this system, a 19 element small deformable mirror was used as wavefront correction element. High resolution images of photo receptors and capillaries of human retina were obtained. In recent two years, at the base of this system a new adaptive optical system for human retina imaging has been developed. The wavefront correction element is a newly developed 37 element deformable mirror. Some modifications have been adopted for easy operation. Experiments for different imaging wavelengths and axial positions were conducted. Mosaic pictures of photoreceptors and capillaries were obtained. 100 normal and abnormal eyes of different ages have been inspected.The first report in the world concerning the most detailed capillary distribution images cover ±3° by ± 3° field around the fovea has been demonstrated. Some preliminary very early diagnosis experiment has been tried in laboratory. This system is being planned to move to the hospital for clinic experiments.

Molecular imaging of retinal endothelial injury in diabetic animals

Directory of Open Access Journals (Sweden)

Sonja Frimmel

2017-01-01

Conclusion: Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.

Neurotransmitter-Regulated Regeneration in the Zebrafish Retina

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Mahesh B. Rao

2017-04-01

Full Text Available Summary: Current efforts to repair damaged or diseased mammalian retinas are inefficient and largely incapable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage using Müller glia (MG-derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. We show that inhibition of γ-aminobutyric acid (GABA signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect decreased ambient levels and undergo dedifferentiation. Using pharmacological and genetic approaches, we demonstrate that GABAA receptor inhibition stimulates regeneration in undamaged retinas while activation inhibits regeneration in damaged retinas. : Unlike mammals, zebrafish regenerate following retina damage from a resident adult stem cell (Müller glia. Dissecting the mechanisms that zebrafish use could lead to new therapeutic targets to treat retinal diseases. Patton and colleagues have discovered a mechanism by which decreased GABA levels are sensed by Müller glia to initiate a regenerative response. Keywords: zebrafish, retina, regeneration, Müller glia, GABA

Corpus vitreum, retina og chorioidea biopsi

DEFF Research Database (Denmark)

Scherfig, Erik Christian Høegh

2002-01-01

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

Angiogenic Factors and Cytokines in Diabetic Retinopathy

Science.gov (United States)

Abcouwer, Steven F.

2013-01-01

Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DR-associated vascular dysfunction, edema and angiogenesis. This has stimulated research of alternative therapeutic targets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored. PMID:24319628

Diabetes and the eye

African Journals Online (AJOL)

2007-10-11

Oct 11, 2007 ... Diabetic damage is not limited to the lens and retina, but also includes other orbital ... A high index of suspicion and prompt referral to an ear, nose and ... retinal detachment. 'Cotton ... the risk of visual loss by 90%.2. The aim ...

Review Article. Electrophysiological Methods for Study of Changes in Visual Analyzer in Patients with Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Elena Mermeklieva

2017-03-01

Full Text Available The electrophysiological (EF methods are objective methods for studying the visual analyzer function. These include electroretinography (ERG, electrooculography (EOG and visual evoked potentials (VEPs. ERG and EOG are used for diagnosis and monitoring of a number of diseases of the retina. VEPs depend on the functional integrity of the entire optical path from the retina through the optic nerve, optic tract, the optical radiation to the visual cortex. The electrophysiological methods are widely used in studying the function of the visual analyzer in the ophthalmic and neurological practice, for objectively measuring the visual acuity and the visual field in non-cooperative patients, small children and in simulation. Diabetes mellitus (DM is a group of metabolic diseases characterized by hyperglycemia. One of the late complications of DM is diabetic retinopathy (DR. It is one of the most serious complications of diabetes, often leading to blindness. Nowadays, DR includes retinal neurodegeneration and microvascular complications. By EF studies can evaluate the function of the retina in diabetic patients in an objective manner using ERG, that reflects the EF activity of the neurons in the retina and VEPs, which indicate the electrical conductivity across the optic tract to the visual cortex.

Distribution and protective function of pituitary adenylate cyclase-activating polypeptide (PACAP in the retina

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Tomoya eNakamachi

2012-11-01

Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP, which is found in 27- or 38-amino acid forms, belongs to the VIP/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues, with PACAP known to exert a protective effect against several types of neural damage. The retina is considered to be part of the central nervous system, and retinopathy is a common cause of profound and intractable loss of vision. This review will examine the expression and morphological distribution of PACAP and its receptors in the retina, and will summarize the current state of knowledge regarding the protective effect of PACAP against different kinds of retinal damage, such as that identified in association with diabetes, ultraviolet light, hypoxia, optic nerve transection, and toxins. This article will also address PACAP-mediated protective pathways involving retinal glial cells.

Msx1 is expressed in retina endothelial cells at artery branching sites

OpenAIRE

Miguel Lopes; Olivier Goupille; Cécile Saint Cloment; Benoît Robert

2012-01-01

Summary Msx1 and Msx2 encode homeodomain transcription factors that play a role in several embryonic developmental processes. Previously, we have shown that in the adult mouse, Msx1lacZ is expressed in vascular smooth muscle cells (VSMCs) and pericytes, and that Msx2lacZ is also expressed in VSMCs as well as in a few endothelial cells (ECs). The mouse retina and choroid are two highly vascularized tissues. Vessel alterations in the retina are associated with several human diseases and the ret...

Blood Vessel Enhancement and Segmentation for Screening of Diabetic Retinopathy

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Ibaa Jamal

2012-06-01

Full Text Available Diabetic retinopathy is an eye disease caused by the increase of insulin in blood and it is one of the main cuases of blindness in idusterlized countries. It is a progressive disease and needs an early detection and treatment. Vascular pattern of human retina helps the ophthalmologists in automated screening and diagnosis of diabetic retinopathy. In this article, we present a method for vascular pattern ehnacement and segmentation. We present an automated system which uses wavelets to enhance the vascular pattern and then it applies a piecewise threshold probing and adaptive thresholding for vessel localization and segmentation respectively. The method is evaluated and tested using publicly available retinal databases and we further compare our method with already proposed techniques.

Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice.

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Alexandra Saliba

Full Text Available Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in retinas of albino rats. Here, we test the hypothesis that photobiomodulation (PBM is effective in diabetic, pigmented mice, even when delayed until weeks after onset of diabetes. Direct and indirect effects of PBM on the retina also were studied.Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm daily. In one study, mice were diabetic for 4 weeks before initiation of PBM for an additional 10 weeks. Retinal oxidative stress, inflammation, and retinal function were measured. In some mice, heads were covered with a lead shield during PBM to prevent direct illumination of the eye, or animals were treated with an inhibitor of heme oxygenase-1. In a second study, PBM was initiated immediately after onset of diabetes, and administered daily for 2 months. These mice were examined using manganese-enhanced MRI to assess effects of PBM on transretinal calcium channel function in vivo.PBM intervention improved diabetes-induced changes in superoxide generation, leukostasis, expression of ICAM-1, and visual performance. PBM acted in part remotely from the retina because the beneficial effects were achieved even with the head shielded from the light therapy, and because leukocyte-mediated cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers.PBM induces retinal protection against abnormalities induced by diabetes in pigmented animals, and even as an intervention. Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms. PBM is a novel non-pharmacologic treatment strategy to inhibit early changes of diabetic

Segmentasi Pembuluh Darah Retina Pada Citra Fundus Menggunakan Gradient Based Adaptive Thresholding Dan Region Growing

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Deni Sutaji

2016-07-01

Full Text Available AbstrakSegmentasi pembuluh darah pada citra fundus retina menjadi hal yang substansial dalam dunia kedokteran, karena dapat digunakan untuk mendeteksi penyakit, seperti: diabetic retinopathy, hypertension, dan cardiovascular. Dokter membutuhkan waktu sekitar dua jam untuk mendeteksi pembuluh darah retina, sehingga diperlukan metode yang dapat membantu screening agar lebih cepat.Penelitian sebelumnya mampu melakukan segmentasi pembuluh darah yang sensitif terhadap variasi ukuran lebar pembuluh darah namun masih terjadi over-segmentasi pada area patologi. Oleh karena itu, penelitian ini bertujuan untuk mengembangkan metode segmentasi pembuluh darah pada citra fundus retina yang dapat mengurangi over-segmentasi pada area patologi menggunakan Gradient Based Adaptive Thresholding dan Region Growing.Metode yang diusulkan terdiri dari 3 tahap, yaitu segmentasi pembuluh darah utama, deteksi area patologi dan segmentasi pembuluh darah tipis. Tahap segmentasi pembuluh darah utama menggunakan high-pass filtering dan tophat reconstruction pada kanal hijau citra yang sudah diperbaiki kontrasnya sehingga lebih jelas perbedaan antara pembuluh darah dan background. Tahap deteksi area patologi menggunakan metode Gradient Based Adaptive Thresholding. Tahap segmentasi pembuluh darah tipis menggunakan Region Growing berdasarkan informasi label pembuluh darah utama dan label area patologi. Hasil segmentasi pembuluh darah utama dan pembuluh darah tipis kemudian digabungkan sehingga menjadi keluaran sistem berupa citra biner pembuluh darah. Berdasarkan hasil uji coba, metode ini mampu melakukan segmentasi pembuluh darah retina dengan baik pada citra fundus DRIVE, yaitu dengan akurasi rata-rata 95.25% dan nilai Area Under Curve (AUC pada kurva Relative Operating Characteristic (ROC sebesar 74.28%.                           Kata Kunci: citra fundus retina, gradient based adaptive thresholding, patologi, pembuluh darah retina, region growing

Combining Image and Non-Image Data for Automatic Detection of Retina Disease in a Telemedicine Network

Energy Technology Data Exchange (ETDEWEB)

Aykac, Deniz [ORNL; Chaum, Edward [University of Tennessee, Knoxville (UTK); Fox, Karen [Delta Health Alliance; Garg, Seema [University of North Carolina; Giancardo, Luca [ORNL; Karnowski, Thomas Paul [ORNL; Li, Yaquin [University of Tennessee, Knoxville (UTK); Nichols, Trent L [ORNL; Tobin Jr, Kenneth William [ORNL

2011-01-01

A telemedicine network with retina cameras and automated quality control, physiological feature location, and lesion/anomaly detection is a low-cost way of achieving broad-based screening for diabetic retinopathy (DR) and other eye diseases. In the process of a routine eye-screening examination, other non-image data is often available which may be useful in automated diagnosis of disease. In this work, we report on the results of combining this non-image data with image data, using the protocol and processing steps of a prototype system for automated disease diagnosis of retina examinations from a telemedicine network. The system includes quality assessments, automated physiology detection, and automated lesion detection to create an archive of known cases. Non-image data such as diabetes onset date and hemoglobin A1c (HgA1c) for each patient examination are included as well, and the system is used to create a content-based image retrieval engine capable of automated diagnosis of disease into 'normal' and 'abnormal' categories. The system achieves a sensitivity and specificity of 91.2% and 71.6% using hold-one-out validation testing.

A novel approach of proteomics to study the mechanism of action of grape seed proanthocyanidin extracts on diabetic retinopathy in rats

Institute of Scientific and Technical Information of China (English)

无

2008-01-01

Background Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes. Methods We used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats. Results GSPE significantly reduced the AGEs of diabetic rats (P <0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism. Conclusions These findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.

Towards metabolic mapping of the human retina.

Science.gov (United States)

Schweitzer, D; Schenke, S; Hammer, M; Schweitzer, F; Jentsch, S; Birckner, E; Becker, W; Bergmann, A

2007-05-01

Functional alterations are first signs of a starting pathological process. A device that measures parameter for the characterization of the metabolism at the human eye-ground would be a helpful tool for early diagnostics in stages when alterations are yet reversible. Measurements of blood flow and of oxygen saturation are necessary but not sufficient. The new technique of auto-fluorescence lifetime measurement (FLIM) opens in combination with selected excitation and emission ranges the possibility for metabolic mapping. FLIM not only adds an additional discrimination parameter to distinguish different fluorophores but also resolves different quenching states of the same fluorophore. Because of its high sensitivity and high temporal resolution, its capability to resolve multi-exponential decay functions, and its easy combination with laser scanner ophthalmoscopy, multi-dimensional time-correlated single photon counting was used for fundus imaging. An optimized set up for in vivo lifetime measurements at the human eye-ground will be explained. In this, the fundus fluorescence is excited at 446 or 468 nm and the time-resolved autofluorescence is detected in two spectral ranges between 510 and 560 nm as well as between 560 and 700 nm simultaneously. Exciting the fundus at 446 nm, several fluorescence maxima of lifetime t1 were detected between 100 and 220 ps in lifetime histograms of 40 degrees fundus images. In contrast, excitation at 468 nm results in a single maximum of lifetime t1 = 190 +/- 16 ps. Several fundus layers contribute to the fluorescence intensity in the short-wave emission range 510-560 nm. In contrast, the fluorescence intensity in the long-wave emission range between 560 and 700 nm is dominated by the fluorescence of lipofuscin in the retinal pigment epithelium. Comparing the lateral distribution of parameters of a tri-exponential model function in lifetime images of the fundus with the layered anatomical fundus structure, the shortest component (t1

Diabetic Retinopathy: Clinical Findings and Management

Directory of Open Access Journals (Sweden)

DD Murray McGavin

2003-01-01

Full Text Available Diabetes mellitus is a metabolic abnormality in which there is a failure to utilise glucose and hence a state of hyperglycaemia can occur. If hyperglycaemia continues uncontrolled over time, it will lead to significant and widespread pathological changes, including involvement of the retina, brain and kidney.In industrialised countries, approximately 1% of the population is diabetic, and at least another 1% are undiagnosed diabetics. Insulin dependent diabetes (IDDM, accounts for approximately 10-15% of cases, the remainder being maturity onset or non-insulin dependent diabetics (NIDDM. Diabetes mellitus is an international public health problem with estimated prevalences ranging from 2.0% to 11.7% in studied populations across the world.

Selective retina therapy (SRT); Selektive Retina-Therapie (SRT)

Energy Technology Data Exchange (ETDEWEB)

Brinkmann, R.; Birngruber, R. [Luebeck Univ. (Germany). Inst. fuer Biomedizinische Optik; Medizinisches Laserzentrum Luebeck GmbH, Luebeck (Germany)

2007-07-01

Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Luebeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the choroid. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced. (orig.)

An analog VLSI chip emulating polarization vision of Octopus retina.

Science.gov (United States)

Momeni, Massoud; Titus, Albert H

2006-01-01

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

Neurodegeneration in the diabetic eye

DEFF Research Database (Denmark)

Simó, Rafael; Hernández, Cristina; Bandello, F

2014-01-01

Diabetic retinopathy (DR), one of the leading causes of preventable blindness, has been considered a microcirculatory disease of the retina. However, there is emerging evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the develop...

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

Directory of Open Access Journals (Sweden)

Rezty Amalia Aras

2016-05-01

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

La retina para el médico no oftalmólogo

Directory of Open Access Journals (Sweden)

Clara Leonor Varón Plata, MD

2010-01-01

Full Text Available La retina es un tejido fundamental en el órgano de la visión.En este artículo hacemos una revisión sobre la anatomía yfisiología de esta estructura así como sobre las principalespatologías que la pueden afectar, entre ellas: despren-dimiento de retina, retinopatía diabética y la enfermedadmacular relacionada con la edad. Aunque actualmentecontamos con técnicas médicas y quirúrgicas seguras yefectivas para el manejo de estas patologías, aúnrepresentan un reto para la ciencia médica, y en estadosavanzados comprometen seriamente la función visual, porello es de gran importancia que el médico general tengaclaros los conceptos básicos sobre el diagnóstico de estasenfermedades, para realizar una remisión adecuada y así poder evitar al máximo secuelas visuales en el paciente. En este artículo revisamos libros de texto reconocidos y empleando MEDLINE, algunos artículos representativos sobre este tema, para mostrar un panorama general del estado actual, clínico e investigativo, del diagnóstico y tratamientode las enfermedades más importantes que afectan la retina y el vítreo. ______________________________________________________________________The retina is a fundamental tissue of the visual organ. In this article we make a review of the anatomy and physiology of this structure as well as the main pathologies that may affect it like: retinal detachment, diabetic retinopathy, and age related macular degeneration. Although currently there are safe medical and surgical alternatives for the management of these diseases, they still represent a challenge for the medical science, and in advanced stagesthey seriously compromise visual function. For this reason it is of vital importance that the primary care physician has clear concepts about the diagnosis of these diseases, to perform an adequate referral, avoiding visual sequelae as much as possible. In this article we reviewed recognized textbooks and using MEDLINE we found some

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

Science.gov (United States)

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

2014-05-13

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

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

Directory of Open Access Journals (Sweden)

Jake Bedore

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

Exploration of the preventive effect of ursolic acid on retinopathy in diabetic mice and its mechanism

Institute of Scientific and Technical Information of China (English)

Ai-Zhong Yu

2016-01-01

Objective:To study the preventive effect of ursolic acid on retinopathy in diabetic mice through adjusting insulin sensitivity, glucose transport, angiogenesis and inflammation. Methods:Male C57BL/6 mice were selected as experimental animals and randomly divided into control group (N group), model group (D group) and intervention group (D+UA group), D group and D+UA group established diabetes models through intraperitoneal injection of STZ, D+UA group received intragastric administration of ursolic acid, and then insulin sensitivity, glucose metabolism in retina as well as the expression levels of GLUTs, HIF-1α/VEGF/VEGFR2 pathway and IKKβ/IKBα/NF-κB pathway in retina tissue of three groups were detected. Results:AUC of D group was significantly lower than that of N group, and HOMA-IR, sugar content in retina tissue as well as GLUT-1, GLUT-3, HIF-1α, VEGF, VEGFR2, IKKβ, IKBα, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin levels were significantly higher than those of N group;AUC of D+UA group was significantly higher than that of D group, and HOMA-IR, sugar content in retina tissue as well as GLUT-1, GLUT-3, HIF-1α, VEGF, VEGFR2, IKK毬, IKBα, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin levels were significantly lower than those of D group. Conclusion:Ursolic acid can increase insulin sensitivity, reduce sugar content in retina tissue and inhibit angiogenesis and inflammation degree in retina tissue, and has preventive effect on retinopathy in diabetic mice.

Near UV radiation effect on the lens and retina

International Nuclear Information System (INIS)

Zigman, S.

1987-01-01

The discussion presented in this paper indicates that the retina of a diurnal animal with a natural UV-absorbing lens (ie: the gray squirrel) is susceptible to near-UV damage from environmental sources only after the lens has been removed. This suggests that it is very important to protect against near-UV exposure of human eyes after cataract surgery

Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina

Science.gov (United States)

Zhang, Yan; Rha, Jungtae; Jonnal, Ravi S.; Miller, Donald T.

2005-06-01

Although optical coherence tomography (OCT) can axially resolve and detect reflections from individual cells, there are no reports of imaging cells in the living human retina using OCT. To supplement the axial resolution and sensitivity of OCT with the necessary lateral resolution and speed, we developed a novel spectral domain OCT (SD-OCT) camera based on a free-space parallel illumination architecture and equipped with adaptive optics (AO). Conventional flood illumination, also with AO, was integrated into the camera and provided confirmation of the focus position in the retina with an accuracy of ±10.3 μm. Short bursts of narrow B-scans (100x560 μm) of the living retina were subsequently acquired at 500 Hz during dynamic compensation (up to 14 Hz) that successfully corrected the most significant ocular aberrations across a dilated 6 mm pupil. Camera sensitivity (up to 94 dB) was sufficient for observing reflections from essentially all neural layers of the retina. Signal-to-noise of the detected reflection from the photoreceptor layer was highly sensitive to the level of cular aberrations and defocus with changes of 11.4 and 13.1 dB (single pass) observed when the ocular aberrations (astigmatism, 3rd order and higher) were corrected and when the focus was shifted by 200 μm (0.54 diopters) in the retina, respectively. The 3D resolution of the B-scans (3.0x3.0x5.7 μm) is the highest reported to date in the living human eye and was sufficient to observe the interface between the inner and outer segments of individual photoreceptor cells, resolved in both lateral and axial dimensions. However, high contrast speckle, which is intrinsic to OCT, was present throughout the AO parallel SD-OCT B-scans and obstructed correlating retinal reflections to cell-sized retinal structures.

Information processing in the outer retina of fish

NARCIS (Netherlands)

Endeman, D.

2017-01-01

The retina translates light into neuronal activity. Thus, it renders visual information of the external environment. The retina can only send a limited amount of information to the brain within a given period. To use this amount optimally, light stimuli are strongly processed in the retina. This

The Ubiquitin-Proteasome System and Microvascular Complications of Diabetes

Directory of Open Access Journals (Sweden)

Saeed Yadranji Aghdam

2013-01-01

Full Text Available The ubiquitin-proteasome system (UPS is the mainstay of protein quality control which regulates cell cycle, differentiation and various signal transduction pathways in eukaryotic cells. The timely and selective degradation of surplus and/or aberrant proteins by the UPS is essential for normal cellular physiology. Any disturbance, delay or exaggeration in the process of selection, sequestration, labeling for degradation and degradation of target proteins by the UPS will compromise cellular and tissue homeostasis. High blood glucose or hyperglycemia caused by diabetes disrupts normal vascular function in several target organs including the retina and kidney resulting in the development of diabetic retinopathy (DR and diabetic nephropathy (DN. We and others have shown that hyperglycemia and oxidative stress modulate UPS activity in the retina and kidney. The majority of studies have focused on the kidney and provided insights into the contribution of dysregulated UPS to microvascular damage in DN. The eye is a unique organ in which a semi-fluid medium, the vitreous humor, separates the neural retina and its anastomosed blood vessels from the semi-solid lens tissue. The complexity of the cellular and molecular components of the eye may require a normal functioning and well tuned UPS for healthy vision. Altered UPS activity may contribute to the development of retinal microvascular complications of diabetes. A better understanding of the molecular nature of the ocular UPS function under normal and diabetic conditions is essential for development of novel strategies targeting its activity. This review will discuss the association of retinal vascular cell UPS activity with microvascular damage in DR with emphasis on alterations of the PA28 subunits of the UPS.

An analog silicon retina with multichip configuration.

Science.gov (United States)

Kameda, Seiji; Yagi, Tetsuya

2006-01-01

The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

Expression and mechanism of high mobility group box protein-1 in retinal tissue of diabetic rats

Directory of Open Access Journals (Sweden)

Shuang Jiang

2016-05-01

Full Text Available AIM:To investigate the expression and mechanism of high mobility group box protein-1(HMGB1in the retina of diabetic rats. METHODS:Sixty SD rats were randomly divided into diabetic group and control group. Diabetic rat model was produced by intraperitioneal injection of 1% STZ with 60mg/Kg weight. The rats in control group received intraperitioneal injection of normal saline with same dosage. After injection, the rats were sacrificed and eyeballs were enucleated for HE staining, the retina fluorescence angiography, TUNEL and Western Blot detection at 1, 2 and 4mo for the expressions of HMGB1 and NF-κB. RESULTS:Compared with the control group, the retinal cells disorder, cell densities decreases, microvasculars occlusion were founded with inner and outer nuclear layer thinning and ganglion cell apoptosis. The fluorescence angiography showed that peripheral capillaries became circuitous and vascular occlusion and non-perfusion area could be seen. The expressions of HMGB1 and NF-κB were higher than those of control with time dependence and they had significant positive correlations(PCONCLUSION:The expression of HMGB1 increases in diabetic rat retina, which may involve in the occurrence of diabetic retinopathy through the NF- κB pathway.

The role of high mobility group box 1 (HMGB-1) in the diabetic retinopathy inflammation and apoptosis.

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Yu, Yao; Yang, Lu; Lv, Jinlei; Huang, Xu; Yi, Jinglin; Pei, Chonggang; Shao, Yi

2015-01-01

Diabetic Retinopathy (DR) is one of the most common complications of the late phase diabetes, and also a common cause of blindness. High mobility group box 1 (HMGB-1) is considered to be an inflammatory mediator in the late phase that promotes inflammation and neovascularization in diabetes. Therefore, this paper discussed the role of HMGB-1 in diabetic retinopathy inflammation and neovascularization. 96 adult SD rats were randomly divided into control and diabetes group. The diabetic rat model was established by intraperitoneal injection of streptomycin (0.1 mol/L). Western blot was applied to determine HMGB-1 and its receptor RAGE and TLR2 protein expression in the serum. TUNEL was used to detect retinal apoptosis. Immunofluorescence was performed to test HMGB1 protein expression in retina. HBGM-1 and RAGE expression in diabetic rat retina was significantly higher than the control (P detection showed that diabetic rat retinal cells presented obviously higher apoptosis rate (P diabetic rat retinal cells (P diabetic retinopathy by binding with RAGE receptor to accelerate rat retinal cells apoptosis.

Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

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Gramlich, Oliver W; Beck, Sabine; von Thun Und Hohenstein-Blaul, Nadine; Boehm, Nils; Ziegler, Anika; Vetter, Jan M; Pfeiffer, Norbert; Grus, Franz H

2013-01-01

There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group). A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007). Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004). CD27(+) cells and CD27(+)/IgG(+) plasma cells were observed in all glaucomatous subjects, but not in controls. This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an immunological involvement comparable to other

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

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Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-09-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

[Analysis of disability due to ocular complications of diabetes in Tashkent over a ten-year period].

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Dzhamalova, Sh A; Iskandarova, Sh T; Nabiev, A M

2016-01-01

to study peculiarities of primary and recurrent disability due to ocular complications of diabetes in Tashkent over the years 2003-2012 and to assess the impact of risk factors on the effectiveness of laser photocoagulation of the retina. A total of 347 disability examination reports of diabetic patients with ocular complications were copied and 48 case histories of patients with type II diabetes who underwent laser photocoagulation of the retina - retrospectively analyzed. Stabilization of visual function was used as the effectiveness criterion. The rate of new cases of disability over the studied decade averaged 0.55 per 100,000 population per year, while that of recurrent disability was 1.8 times higher - 0.97. The overall rate of disability was not high - 1.53; at that, severe disability (i.e. grade I and II) prevailed. Both recurrent and primary disability groups were made up by middle-aged patients and those in their retirement age; however, in the recurrent disability group the number of young disabled people was 4.5 times higher than in the primary disability group. Studies of the effectiveness of laser photocoagulation of the retina in relation to the compensation of diabetes and blood pressure level showed that unstable general condition was associated with not only significant deterioration of visual function, but also complications, including severe. The rate of disability due to ocular complications of diabetes is generally not high, however, grades I and II disabilities that require greater social support has been found to prevail in both groups. Most of disabled people are middle-aged (working-age population), which also causes economic damage. In cases of decompensated diabetes and unstable blood pressure, the effectiveness of laser photocoagulation of the retina is reduced.

Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

DEFF Research Database (Denmark)

Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J

2010-01-01

. Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag...... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies......Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control...

Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection.

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Huang, Di; Chen, Ying-Shan; Thakur, Sachin S; Rupenthal, Ilva D

2017-10-01

Intravitreal injection is the most common administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient delivery of drugs administered intravitreally. This study aimed to improve the diffusive mobility of nanoparticles (NPs) in the vitreous and enhance their permeation across the retina after intravitreal injection by application of ultrasound (US). Ex vivo posterior bovine eye cups were used and the vitreous was either left intact or removed gently from the neural retina. Hyaluronic acid coated human serum albumin NPs were administered into the eye cups and continuous US with a frequency of 1MHz, an intensity of 0.5W/cm 2 , and a duration of 30s was applied once or repeatedly via the transscleral route. After pre-determined time points, fluorescence intensities in the vitreous and the retina were analyzed. Short pulses of US significantly improved the diffusive mobility of NPs through the vitreous as well as their penetration across the neural retina into the retinal pigment epithelium and choroid without causing any detectable damage to the ocular tissues. Therefore, transscleral US could be a powerful and safe tool to enhance retinal delivery of intravitreally injected NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Human leukocyte antigen (HLA) polymorphism and type 1 diabetes ...

African Journals Online (AJOL)

Insulin-dependent diabetes mellitus or type 1 diabetes is an autoimmune multifactorial disease which has a great socio-economic impact. In Morocco, less is known about the contribution of Human leukocyte antigen (HLA) alleles to type 1 diabetes susceptibility. Our study focused on evaluating the distribution of class II ...

Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod Rhodopsin in the Human Retina.

Directory of Open Access Journals (Sweden)

Martin Ehler

Full Text Available We introduce and describe a novel non-invasive in-vivo method for mapping local rod rhodopsin distribution in the human retina over a 30-degree field. Our approach is based on analyzing the brightening of detected lipofuscin autofluorescence within small pixel clusters in registered imaging sequences taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO over a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying variational optimization techniques from applied mathematics. The physical model and the numerical analysis with its implementation are outlined in detail. This new technique enables the creation of spatial maps of the retinal rhodopsin and retinal pigment epithelium (RPE bisretinoid distribution with an ≈ 50μm resolution.

Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod Rhodopsin in the Human Retina

Science.gov (United States)

Ehler, Martin; Dobrosotskaya, Julia; Cunningham, Denise; Wong, Wai T.; Chew, Emily Y.; Czaja, Wojtek; Bonner, Robert F.

2015-01-01

We introduce and describe a novel non-invasive in-vivo method for mapping local rod rhodopsin distribution in the human retina over a 30-degree field. Our approach is based on analyzing the brightening of detected lipofuscin autofluorescence within small pixel clusters in registered imaging sequences taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO) over a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying variational optimization techniques from applied mathematics. The physical model and the numerical analysis with its implementation are outlined in detail. This new technique enables the creation of spatial maps of the retinal rhodopsin and retinal pigment epithelium (RPE) bisretinoid distribution with an ≈ 50μm resolution. PMID:26196397

DIAGNOSIS OF DIABETIC RETINOPATHY USING MACHINE LEARNING TECHNIQUES

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R. Priya

2013-07-01

Full Text Available Diabetic retinopathy (DR is an eye disease caused by the complication of diabetes and we should detect it early for effective treatment. As diabetes progresses, the vision of a patient may start to deteriorate and lead to diabetic retinopathy. As a result, two groups were identified, namely non-proliferative diabetic retinopathy (NPDR and proliferative diabetic retinopathy (PDR. In this paper, to diagnose diabetic retinopathy, three models like Probabilistic Neural network (PNN, Bayesian Classification and Support vector machine (SVM are described and their performances are compared. The amount of the disease spread in the retina can be identified by extracting the features of the retina. The features like blood vessels, haemmoraghes of NPDR image and exudates of PDR image are extracted from the raw images using the image processing techniques and fed to the classifier for classification. A total of 350 fundus images were used, out of which 100 were used for training and 250 images were used for testing. Experimental results show that PNN has an accuracy of 89.6 % Bayes Classifier has an accuracy of 94.4% and SVM has an accuracy of 97.6%. This infers that the SVM model outperforms all other models. Also our system is also run on 130 images available from “DIARETDB0: Evaluation Database and Methodology for Diabetic Retinopathy” and the results show that PNN has an accuracy of 87.69% Bayes Classifier has an accuracy of 90.76% and SVM has an accuracy of 95.38%.

Modified saponification and HPLC methods for analyzing carotenoids from the retina of quail: implications for its use as a nonprimate model species.

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Toomey, Matthew B; McGraw, Kevin J

2007-09-01

To investigate carotenoid content in the retina of Japanese quail (Coturnix japonica), for comparison with carotenoids in human retina, and to assess the effects of different saponification procedures on the recovery of quail retinal carotenoids. Extracted retinal carotenoids were saponified with methods adapted from recent studies, then identified and quantified with reverse-phase high-performance liquid chromatography (HPLC). To assess the effects of saponification conditions on carotenoid recovery from quail retina, we varied base concentration and the total time of saponification across a wide range and again used HPLC to compare carotenoid concentrations among conditions. Astaxanthin and galloxanthin were the dominant carotenoids recovered in the quail retina, along with smaller amounts of five other carotenoids (lutein, zeaxanthin, 3'-epilutein, epsilon-carotene, and an unidentified carotenoid). Astaxanthin was sensitive to saponification conditions; recovery was poor with strong bases (0.2 and 0.5 M KOH) and best with weak bases (0.01 and 0.2 M KOH). In contrast, xanthophyll carotenoids (galloxanthin, zeaxanthin, lutein, 3'-epilutein, and the unknown) were best recovered with strong base after 6 hours of saponification at room temperature. The recovery of epsilon-carotene was not affected by saponification conditions. Separate chemical hydrolysis procedures--using a strong base to recover xanthophylls and a weak base to recover astaxanthin--should be used for maximizing recovery of quail retinal carotenoids. Because the dominant carotenoids in quail retina are absent in human retina, and because of their different packaging (e.g., esterified in oil droplets) and light-absorbance properties compared with xanthophylls in the human eye, use of the quail as a model organism for studying human retinal carotenoids should be approached with caution.

Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats.

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Bucolo, Claudio; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore

2012-07-01

Diabetic retinopathy is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. We hypothesized that eriodictyol, one of the most abundant dietary flavonoids, could be effective against diabetic retinopathy, which involves significant oxidative stress and inflammation. The aim of the present study was to investigate the effects of eriodictyol in early retinal and plasma changes of streptozotocin-induced diabetic rats. The effect of eriodictyol treatment (0.1, 1, 10 mg/kg daily for 10 days) was evaluated by TNF-α, ICAM-1, VEGF, and eNOS protein levels measurement in the retina, plasma lipid peroxidation, and blood-retinal barrier (BRB) integrity. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina from diabetic rats. Eriodictyol treatment significantly lowered retinal TNF-α, ICAM-1, VEGF, and eNOS in a dose-dependent manner. Further, treatment with eriodictyol significantly suppressed diabetes-related lipid peroxidation, as well as the BRB breakdown. These data demonstrated that eriodictyol attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the BRB in early diabetic rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of Qi Ming Granule on the choroidal circulation in diabetic patients

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Ke-Jun Li

2016-03-01

Full Text Available AIM:To investigate the effect of a Chinese medicine(Qi Ming granuleon the retinal and choroidal circulation in diabetes patients. METHODS: According to the results of fundus fluorescein angiography(FFA, all the 45 diabetes patients were divided into no diabetic retinopathy(NDRgroup and nonproliferative diabetic retinopathy(NPDRgroup. All subjects were examined by FFA and indocyanine green angiography(ICGAat the same time. After taken Qi Ming granule for 3mo, all subjects were examined by the same method. FFA and ICGA were used to evaluate the retinal and choroidal circulation and their features. The key points were filling time for the retinal and choroidal circulation before and after treatments. The accuracy data was used to evaluate the effect.RESULTS: After taken Qi Ming granule for 3mo, there were significant decrease of the retina and the choroid filling time in NDR and NPDR groups. The occurrence rate of various abnormal angiographic features were significantly decreased. CONCLUSION: Qi Ming granule can accelerate the blood flow of retina and choroid, improve the blood circulation in diabetes patients, and delay the occurrence and development of diabetic retinopathy.

Ameliorative effect of Morus alba leaves extract against developmental retinopathy in pups of diabetic and aluminum intoxicated pregnant albino rats

Institute of Scientific and Technical Information of China (English)

Hassan; El-Sayyed; Gamal; Badawy; Sobhy; Hassab; Elnabi; Ibrahim; El-Elaimy; Eman; Al; Shehari

2015-01-01

Objective: To investigate the possible ameliorative effect of crude water extract of Morus alba(M. alba) leaves on retinopathy of rat pups maternally subjected to diabetes and/or Al intoxication.Methods: Both control and experimental groups were subjected to certain integrated approaches, namely, biochemical assessments, light microscopic investigation, transmission electron microscopic investigation, single cell gel electrophoresis(comet assay) and determination of DNA fragmentation.Results: The retina of pups of diabetic and/or Al-intoxicated mothers exhibited abnormal alterations in retinal cell layers including retinal pigmented epithelium, photoreceptor inner segment and ganglion cells. Increased incidence of DNA fragmentation and apoptosis were evident in pups of diabetic and/or Al-intoxicated mothers. However, retina of pups maternally received M. alba extract plus diabetes or Al-intoxicated alone or in combination showed marked amelioration. Less degree of ameliorations was seen in retina of pups maternally subjected to combined treatment. Furthermore, application of crude water extract of M.alba resulted in amelioration of the alterations of maternal serum glucose as well as Al concentration.Conclusions: Based on the results of the present study, M. alba extract is effective against experimentally diabetic and Al-induced developmental retinopathy.

Efferent influences on the bioelectrical activity of the retina in primates.

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Ortiz, Gonzalo; Odom, J Vernon; Passaglia, Christopher L; Tzekov, Radouil T

2017-02-01

The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

Exclusion of aldose reductase as a mediator of ERG deficits in a mouse model of diabetic eye disease.

Science.gov (United States)

Samuels, Ivy S; Lee, Chieh-Allen; Petrash, J Mark; Peachey, Neal S; Kern, Timothy S

2012-11-01

Streptozotocin (STZ)-induced diabetes is associated with reductions in the electrical response of the outer retina and retinal pigment epithelium (RPE) to light. Aldose reductase (AR) is the first enzyme required in the polyol-mediated metabolism of glucose, and AR inhibitors have been shown to improve diabetes-induced electroretinogram (ERG) defects. Here, we used control and AR -/- mice to determine if genetic inactivation of this enzyme likewise inhibits retinal electrophysiological defects observed in a mouse model of type 1 diabetes. STZ was used to induce hyperglycemia and type 1 diabetes. Diabetic and age-matched nondiabetic controls of each genotype were maintained for 22 weeks, after which ERGs were used to measure the light-evoked components of the RPE (dc-ERG) and the neural retina (a-wave, b-wave). In comparison to their nondiabetic controls, wildtype (WT) and AR -/- diabetic mice displayed significant decreases in the c-wave, fast oscillation, and off response components of the dc-ERG but not in the light peak response. Nondiabetic AR -/- mice displayed larger ERG component amplitudes than did nondiabetic WT mice; however, the amplitude of dc-ERG components in diabetic AR -/- animals were similar to WT diabetics. ERG a-wave amplitudes were not reduced in either diabetic group, but b-wave amplitudes were lower in WT and AR -/-diabetic mice. These findings demonstrate that the light-induced responses of the RPE and outer retina are disrupted in diabetic mice, but these defects are not due to photoreceptor dysfunction, nor are they ameliorated by deletion of AR. This latter finding suggests that benefits observed in other studies utilizing pharmacological inhibitors of AR might have been secondary to off-target effects of the drugs.

Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

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Harshini Chakravarthy

Full Text Available Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs. We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

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

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

2016-01-01

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

Skin and diabetes mellitus: what do we know?

Science.gov (United States)

Quondamatteo, Fabio

2014-01-01

Diabetes mellitus (DM) is becoming increasingly prevalent worldwide. Although major complications of this condition involve kidney, retina and peripheral nerves, the skin of diabetic patients is also frequently injured. Hence, interest is mounting in the definition of the structural and molecular profile of non-complicated diabetic skin, i.e., before injuries occur. Most of the available knowledge in this area has been obtained relatively recently and, in part, derives from various diabetic animal models. These include both insulin-dependent and insulin-resistant models. Structural work in human diabetic skin has also been carried out by means of tissue samples or of non-invasive methods. Indications have indeed been found for molecular/structural changes in diabetic skin. However, the overall picture that emerges is heterogeneous, incomplete and often contradictory and many questions remain unanswered. This review aims to detail, as much as possible, the various pieces of current knowledge in a systematic and synoptic manner. This should aid the identification of areas in which key questions are still open and more research is needed. A comprehensive understanding of this field could help in determining molecular targets for the prevention and treatment of skin injuries in DM and markers for the monitoring of cutaneous and systemic aspects of the disease. Additionally, with the increasing development of non-invasive optics-based deep-tissue-imaging diagnostic technologies, precise knowledge of cutaneous texture and molecular structure becomes an important pre-requisite for the use of such methods in diabetic patients.

Retina neural circuitry seen with particle detector technology

CERN Multimedia

CERN Bulletin

2010-01-01

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

The cone-dominant retina and the inner ear of zebrafish express the ortholog of CLRN1, the causative gene of human Usher syndrome type 3A.

Science.gov (United States)

Phillips, Jennifer B; Västinsalo, Hanna; Wegner, Jeremy; Clément, Aurélie; Sankila, Eeva-Marja; Westerfield, Monte

2013-12-01

Clarin-1 (CLRN1) is the causative gene in Usher syndrome type 3A, an autosomal recessive disorder characterized by progressive vision and hearing loss. CLRN1 encodes Clarin-1, a glycoprotein with homology to the tetraspanin family of proteins. Previous cell culture studies suggest that Clarin-1 localizes to the plasma membrane and interacts with the cytoskeleton. Mouse models demonstrate a role for the protein in mechanosensory hair bundle integrity, but the function of Clarin-1 in hearing remains unclear. Even less is known of its role in vision, because the Clrn1 knockout mouse does not exhibit a retinal phenotype and expression studies in murine retinas have provided conflicting results. Here, we describe cloning and expression analysis of the zebrafish clrn1 gene, and report protein localization of Clarin-1 in auditory and visual cells from embryonic through adult stages. We detect clrn1 transcripts as early as 24h post-fertilization, and expression is maintained through adulthood. In situ hybridization experiments show clrn1 transcripts enriched in mechanosensory hair cells and supporting cells of the inner ear and lateral line organ, photoreceptors, and cells of the inner retina. In mechanosensory hair cells, Clarin-1 is polarized to the apical cell body and the synapses. In the retina, Clarin-1 localizes to lateral cell contacts between photoreceptors and is associated with the outer limiting membrane and subapical processes emanating from Müller glial cells. We also find Clarin-1 protein in the outer plexiform, inner nuclear and ganglion cell layers of the retina. Given the importance of Clarin-1 function in the human retina, it is imperative to find an animal model with a comparable requirement. Our data provide a foundation for exploring the role of Clarin-1 in retinal cell function and survival in a diurnal, cone-dominant species. Copyright © 2013 Elsevier B.V. All rights reserved.

Detection and classification of retinal lesions for grading of diabetic retinopathy.

Science.gov (United States)

Usman Akram, M; Khalid, Shehzad; Tariq, Anam; Khan, Shoab A; Azam, Farooque

2014-02-01

Diabetic Retinopathy (DR) is an eye abnormality in which the human retina is affected due to an increasing amount of insulin in blood. The early detection and diagnosis of DR is vital to save the vision of diabetes patients. The early signs of DR which appear on the surface of the retina are microaneurysms, haemorrhages, and exudates. In this paper, we propose a system consisting of a novel hybrid classifier for the detection of retinal lesions. The proposed system consists of preprocessing, extraction of candidate lesions, feature set formulation, and classification. In preprocessing, the system eliminates background pixels and extracts the blood vessels and optic disc from the digital retinal image. The candidate lesion detection phase extracts, using filter banks, all regions which may possibly have any type of lesion. A feature set based on different descriptors, such as shape, intensity, and statistics, is formulated for each possible candidate region: this further helps in classifying that region. This paper presents an extension of the m-Mediods based modeling approach, and combines it with a Gaussian Mixture Model in an ensemble to form a hybrid classifier to improve the accuracy of the classification. The proposed system is assessed using standard fundus image databases with the help of performance parameters, such as, sensitivity, specificity, accuracy, and the Receiver Operating Characteristics curves for statistical analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human genetics of diabetic vascular complications

Indian Academy of Sciences (India)

Abstract. Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the ..... cohort with nominal significance, and a recent meta-analysis ..... Whereas it is generally thought that lysine acetylation is.

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy.

Science.gov (United States)

Loukovaara, Sirpa; Sandholm, Jouko; Aalto, Kristiina; Liukkonen, Janne; Jalkanen, Sirpa; Yegutkin, Gennady G

2017-02-01

Clear signaling roles for ATP and adenosine have been established in all tissues, including the eye. The magnitude of signaling responses is governed by networks of enzymes; however, little is known about the regulatory mechanisms of purinergic signaling in the eye. By employing thin-layer chromatographic assays with 3 H-labeled substrates, this study aimed to evaluate the role of nucleotide homeostasis in the pathogenesis of vitreoretinal diseases in humans. We have identified soluble enzymes ecto-5'-nucleotidase/CD73, adenylate kinase-1, and nucleoside diphosphate kinase in the vitreous fluid that control active cycling between pro-inflammatory ATP and anti-inflammatory adenosine. Strikingly, patients with proliferative form of diabetic retinopathy (DR) had higher adenylate kinase activity and ATP concentration, when compared to non-proliferative DR eyes and non-diabetic controls operated for rhegmatogenous retinal detachment, macular hole, and pucker. The non-parametric correlation analysis revealed positive correlations between intravitreal adenylate kinase and concentrations of ATP, ADP, and other angiogenic (angiopoietins-1 and -2), profibrotic (transforming growth factor-β1), and proteolytic (matrix metalloproteinase-9) factors but not erythropoietin and VEGF. Immunohistochemical staining of postmortem human retina additionally revealed selective expression of ecto-5'-nucleotidase/CD73 on the rod-and-cone-containing photoreceptor cells. Collectively, these findings provide novel insights into the regulatory mechanisms that influence purinergic signaling in diseased eye and open up new possibilities in the development of enzyme-targeted therapeutic approaches for prevention and treatment of DR. Ecto-5'-nucleotidase/CD73 and adenylate kinase-1 circulate in human vitreous fluid. Adenylate kinase activity is high in diabetic eyes with proliferative retinopathy. Diabetic eyes display higher intravitreal ATP/ADP ratio than non-diabetic controls. Soluble adenylate

Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.

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Omori, Yoshihiro; Katoh, Kimiko; Sato, Shigeru; Muranishi, Yuki; Chaya, Taro; Onishi, Akishi; Minami, Takashi; Fujikado, Takashi; Furukawa, Takahisa

2011-01-01

In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.

Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.

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Yoshihiro Omori

Full Text Available In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. We previously reported that Otx2 conditional knockout (CKO mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome of the Otx2 CKO retina, we compared expression profile of Otx2 CKO and wild-type retinas at P1 and P12 using microarray. We observed that expression of 101- and 1049-probe sets significantly decreased in the Otx2 CKO retina at P1 and P12, respectively, whereas, expression of 3- and 4149-probe sets increased at P1 and P12, respectively. We found that expression of genes encoding transcription factors involved in photoreceptor development, including Crx, Nrl, Nr2e3, Esrrb, and NeuroD, was markedly down-regulated in the Otx2 CKO at both P1 and P12. Furthermore, we identified three human retinal disease loci mapped in close proximity to certain down-regulated genes in the Otx2 CKO retina including Ccdc126, Tnfsf13 and Pitpnm1, suggesting that these genes are possibly responsible for these diseases. These transcriptome data sets of the Otx2 CKO retina provide a resource on developing rods and cones to further understand the molecular mechanisms underlying photoreceptor development, function and disease.

Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

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Seong-Jae Kim

2017-08-01

Full Text Available AIM: To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB in retinal ganglion cell (RGC death and analysedthe effect of Aralia elata (AE on neurodegeneration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL diet at the onset of diabetes mellitus (DM. Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT, N-acetyl-b-D-glucosaminidase (OGA, O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P<0.001 vs CTL, P<0.01 vs DM and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (P<0.001 vs CTL, P<0.0001 vs DM, glial activation, and active caspase-3 (P<0.0001 vs CTL, P<0.0001 vs DM were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GlcNAcylation and OGT were increased in diabetic retinas (P<0.0001 vs CTL, and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls (P<0.0001 vs CTL. AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia (P<0.0001 vs DM. CONCLUSION: O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis via downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.

Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

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Oliver W Gramlich

Full Text Available BACKGROUND: There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. METHODS AND RESULTS: Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group. A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007. Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004. CD27(+ cells and CD27(+/IgG(+ plasma cells were observed in all glaucomatous subjects, but not in controls. CONCLUSION: This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an

Radioadaptive Cytoprotective Pathways in the Mouse Retina

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

2010-01-01

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

Imaging of the peripheral retina

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Marcus Kernt

2013-01-01

Full Text Available The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO, digital angiography, optical coherence tomography (OCT, and detection of fundus autofluorescence (FAF have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.

Diabetic brain or retina? Visual psychophysical performance in diabetic patients in relation to GABA levels in occipital cortex.

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Sanches, Mafalda; Abuhaiba, Sulaiman I; d'Almeida, Otília C; Quendera, Bruno; Gomes, Leonor; Moreno, Carolina; Guelho, Daniela; Castelo-Branco, Miguel

2017-06-01

Visual impairment is one of the most feared complications of Type 2 Diabetes Mellitus. Here, we aimed to investigate the role of occipital cortex γ-aminobutyric acid (GABA) as a predictor of visual performance in type 2 diabetes. 18 type 2 diabetes patients were included in a longitudinal prospective one-year study, as well as 22 healthy age-matched controls. We collected demographic data, HbA1C and used a novel set of visual psychophysical tests addressing color, achromatic luminance and speed discrimination in both groups. Psychophysical tests underwent dimension reduction with principle component analysis into three synthetic variables: speed, achromatic luminance and color discrimination. A MEGA-PRESS magnetic resonance brain spectroscopy sequence was used to measure occipital GABA levels in the type 2 diabetes group. Retinopathy grading and retinal microaneurysms counting were performed in the type 2 diabetes group for single-armed correlations. Speed discrimination thresholds were significantly higher in the type 2 diabetes group in both visits; mean difference (95% confidence interval), [0.86 (0.32-1.40) in the first visit, 0.74 (0.04-1.44) in the second visit]. GABA from the occipital cortex predicted speed and achromatic luminance discrimination thresholds within the same visit (r = 0.54 and 0.52; p = 0.02 and 0.03, respectively) in type 2 diabetes group. GABA from the occipital cortex also predicted speed discrimination thresholds one year later (r = 0.52; p = 0.03) in the type 2 diabetes group. Our results suggest that speed discrimination is impaired in type 2 diabetes and that occipital cortical GABA is a novel predictor of visual psychophysical performance independently from retinopathy grade, metabolic control or disease duration in the early stages of the disease.

Adaptation of the Central Retina for High Acuity Vision: Cones, the Fovea and the Avascular Zone

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Provis, Jan M; Dubis, Adam M; Maddess, Ted; Carroll, Joseph

2013-01-01

Presence of a fovea centralis is directly linked to molecular specification of an avascular area in central retina, before the fovea (or `pit') begins to form. Modeling suggests that mechanical forces, generated within the eye, initiate formation of a pit within the avascular area, and its later remodeling in the postnatal period. Within the avascular area the retina is dominated by `midget' circuitry, in which signals are transferred from a single cone to a single bipolar cell, then a single ganglion cell. Thus in inner, central retina there are relatively few lateral connections between neurons. This renders the region adaptable to tangential forces, that translocate of ganglion cells laterally / centrifugally, to form the fovea. Optical coherence tomography enables live imaging of the retina, and shows that there is greater variation in the morphology of foveae in humans than previously thought. This variation is associated with differences in size of the avascular area and appears to be genetically based, but can be modified by environmental factors, including prematurity. Even when the fovea is absent (foveal hypoplasia), cones in central retina adopt an elongated and narrow morphology, enabling them to pack more densely to increase the sampling rate, and to act as more effective waveguides. Given these findings, what then is the adaptive advantage of a fovea? We suggest that the advantages of having a pit in central retina are relatively few, and minor, but together work to enhance acuity. PMID:23500068

Spectral domain optical coherence tomography characteristics in diabetic retinopathy

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Laxmi Gella

2014-01-01

Full Text Available Purpose: To report the appearance of diabetic retinopathy lesions using spectral domain optical coherence tomography (SD-OCT. Materials and Methods: A total of 287 eyes of 199 subjects were included. All the subjects underwent complete ophthalmic examination including SD-OCT. Results: The appearance of various lesions of diabetic retinopathy and the retinal layers involved were reported. In subjects with macular edema the prevalence of incomplete PVD was 55.6%. Conclusion: SD-OCT brings new insights into the morphological changes of the retina in diabetic retinopathy.

Study of diabetic retinopathy and Bone Mineral Density in type 2 Diabetes patient%2型糖尿病患者视网膜病变与骨密度的研究

Institute of Scientific and Technical Information of China (English)

张春香; 赵全良

2014-01-01

目的：探讨2型糖尿病患者视网膜病变（ DR）与骨密度（ BMD）的关系。方法：检查了63例2型糖尿病患者视网膜，分为A组即正常组、B组单纯性视网膜病变组、C组增殖性视网膜病变组，并分别测定其L2～4椎体、双侧股骨Ward 区BMD 。结果：除A组患者BMD与对照组无明显差异（ p ＞0．05）；B、C组患BMD与对照组差异明显（ p ＜0．01）；糖尿病患者中， C组BMD明显低于A组（ p ＜0．01）。结论：糖尿病视网膜病变患者BMD 比正常人低，增殖性视网膜病变组BMD较其它组显著下降。%Objective:To study the relationship between diabetic retinopathy and bone mineral density with type 2 diabetic patients (T2DM) .Methods:Dual energy X -ray absorptiometry was used to measure the bone mineral density (BMD) of lumbar spines(L2 -4) , Ward's triangle in 63 patients with type 2 diabetes mellitus and 55 cases of normal control group .According to diabetic retinopathy were divided into groups with normal retina (group A), nonproliferative diabetic retinopathy (group B) and proliferative diabetic retinopa-thy ( group C) .Results:No significant differences were found in BMD between normal retina l diabetic patients and normal control group ( p >0.05) .BMD was significantly lower in diabetes patient with nonproliferative diabetic retinopathy group and proliferative diabetic retinopathy than the normal control group .In diabetes patient BMD was significantly lower in proliferative diabetic retinopathy group than in normal control groups ( p <0.01) .Conclusion:BMD in diabetes patient with nephropathy should be lower than normal control group.BMD in diabetes patient might be more remarkable in the group with proliferative diabetic retinopathy than in the groups with nor -mal retina and nonproliferative diabetic retinopathy .

Imagen de retina de campo ultra-amplio

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Gerardo García-Aguirre

2017-11-01

Conclusión: Las imágenes de campo ultra-amplio han revolucionado la forma en la que estudiamos y entendemos la enfermedad de la retina. A medida que la tecnología para obtenerlas se haga más accesible, formará parte del armamentario de rutina para estudiar las enfermedades de la retina.

Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice

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Yoo-Ri Chung

2017-01-01

Full Text Available Loss of pericytes, an early hallmark of diabetic retinopathy (DR, results in breakdown of the blood-retinal barrier. Endoplasmic reticulum (ER stress may be involved in this process. The purpose of this study was to examine the effects of ursodeoxycholic acid (UDCA, a known ameliorator of ER stress, on pericyte loss in DR of streptozotocin- (STZ- induced diabetic mice. To assess the extent of DR, the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice were evaluated. Additionally, induction of ER stress and the unfolded protein response (UPR were assessed in diabetic mice and human retinal pericytes exposed to advanced glycation end products (AGE or modified low-density lipoprotein (mLDL. Fluorescein dye leakage during angiography and retinal capillary density were improved in UDCA-treated diabetic mice, compared to the nontreated diabetic group. Among the UPR markers, those involved in the protein kinase-like ER kinase (PERK pathway were increased, while UDCA attenuated UPR in STZ-induced diabetic mice as well as AGE- or mLDL-exposed retinal pericytes in culture. Consequently, vascular integrity was improved and pericyte loss reduced in the retina of STZ-induced diabetic mice. Our findings suggest that UDCA might be effective in protecting against DR.

The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown.

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Reichhart, Nadine; Crespo-Garcia, Sergio; Haase, Nadine; Golic, Michaela; Skosyrski, Sergej; Rübsam, Anne; Herrspiegel, Christina; Kociok, Norbert; Alenina, Natalia; Bader, Michael; Dechend, Ralf; Strauss, Olaf; Joussen, Antonia M

2017-01-01

Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy. Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats. Systemic treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal function was assessed by Ganzfeld electroretinography (ERG). Retinal vessels in TetO rats showed differences in vessel calibre, together with gliosis. The total number and the proportion of activated mononuclear phagocytes was increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG indicated photoreceptor malfunction. Both the inner and outer blood-retina barriers were affected. The ARB treated group showed reduced gliosis and an overall amelioration of retinal function, alongside RGC recovery, whilst no statistically significant differences in vascular and inflammatory features were detected. The TetO rat represents a promising translational model for the early neurovascular changes associated with type 2 diabetic retinopathy. ARB treatment had an effect on the neuronal component of the retina but not on the vasculature.

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

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

2016-02-01

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

Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography

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Campbell, J. P.; Zhang, M.; Hwang, T. S.; Bailey, S. T.; Wilson, D. J.; Jia, Y.; Huang, D.

2017-02-01

Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.

Human genetics of diabetic vascular complications

Indian Academy of Sciences (India)

Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play ...

Excess lead in the neural retina in age-related macular degeneration.

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Erie, Jay C; Good, Jonathan A; Butz, John A

2009-12-01

To measure lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration (AMD). Laboratory investigation. Lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium [RPE]-choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) were determined by using inductively coupled plasma-mass spectrometry. Severity of AMD was graded by using color fundus photographs and the Minnesota Grading System. Differences in metal concentrations were compared by using Wilcoxon rank-sum tests. The neural retinas of subjects with AMD had increased lead concentrations (median, 12.0 ng/g; 25% to 75% interquartile range, 8 to 18 ng/g; n = 25) compared with normal subjects (median, 8.0 ng/g; 25% to 75% interquartile range, 0 to 11 ng/g; P = .04; n = 36). There was no difference in lead concentration in the RPE-choroid complex between subjects with AMD (median, 198 ng/g; 25% to 75% interquartile range, 87 to 381 ng/g) and normal subjects (median, 172 ng/g; 25% to 75% interquartile range, 100 to 288 ng/g; P = .25). Cadmium concentration in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.8 microg/g) and RPE-choroid complex (median, 2.2 microg/g; 25% to 75% interquartile range, 1.8 to 3.7 microg/g) in subjects with AMD was not different from concentrations in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.4 microg/g; P = .32) and RPE-choroid complex (median, 1.5 microg/g; 25% to 75% interquartile range, 0.9 to 2.5 microg/g; P = .12) of normal subjects. AMD is associated with excess lead in the neural retina, and this relationship suggests that metal homeostasis in AMD eyes is different from normal.

Topography of ganglion cell production in the cat's retina

International Nuclear Information System (INIS)

Walsh, C.; Polley, E.H.

1985-01-01

The ganglion cells of the cat's retina form several classes distinguishable in terms of soma size, axon diameter, dendritic morphology, physiological properties, and central connections. Labeling with [ 3 H]thymidine shows that the ganglion cells which survive in the adult are produced as several temporally shifted, overlapping waves: medium-sized cells are produced before large cells, whereas the smallest ganglion cells are produced throughout the period of ganglion cell generation. Large cells and medium-sized cells show the same distinctive pattern of production, forming rough spirals around the area centralis. The oldest cells tend to lie superior and nasal to the area centralis, whereas cells in the inferior nasal retina and inferior temporal retina are, in general, progressively younger. Within each retinal quadrant, cells nearer the area centralis tend to be older than cells in the periphery, but there is substantial overlap. The retinal raphe divides the superior temporal quadrant into two zones with different patterns of cell addition. Superior temporal retina near the vertical meridian adds cells only slightly later than superior nasal retina, whereas superior temporal retina near the horizontal meridian adds cells very late, contemporaneously with inferior temporal retina. The broader wave of production of smaller ganglion cells seems to follow this same spiral pattern at its beginning and end. The presence of the area centralis as a nodal point about which ganglion cell production in the retinal quadrants pivots suggests that the area centralis is already an important retinal landmark even at the earliest stages of retinal development

Characterization of human myotubes from type 2 diabetic and non-diabetic subjects using complementary quantitative mass spectrometric methods

DEFF Research Database (Denmark)

Thingholm, Tine E; Bak, Steffen; Beck-Nielsen, Henning

2011-01-01

2 diabetes. Several abnormalities have been identified in skeletal muscle from type 2 diabetic subjects, however, the exact molecular mechanisms leading to the diabetic phenotype has still not been found. Here we present a large-scale study in which we combine a quantitative proteomic discovery...... strategy using iTRAQ and a label-free study with a targeted quantitative proteomic approach using selected reaction monitoring (SRM) to identify, quantify and validate changes in protein abundance between human myotubes obtained from non-diabetic lean, non-diabetic obese and type 2 diabetic subjects...

Structure of the human vitreoretinal border region

DEFF Research Database (Denmark)

Heegaard, Steffen

1994-01-01

Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human......Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human...

Helping the Retina Regenerate

Science.gov (United States)

... the retina News Brief 03/30/17 A new report gives recommendations for regenerating retinal ganglion cells (RGCs), crucial neurons in the back of the eye that carry visual information to the brain. Authored ...

Detection of early metabolic alterations in the ocular fundus of diabetic patients by time-resolved autofluorescence of endogenous fluorophores

Science.gov (United States)

Schweitzer, D.; Klemm, M.; Quick, S.; Deutsch, L.; Jentsch, S.; Hammer, M.; Dawczynski, J.; Kloos, C. H.; Mueller, U. A.

2011-07-01

Measurements of time-resolved autofluorescence (FLIM) at the human ocular fundus of diabetic patients permit the detection of early pathologic alterations before signs of diabetic retinopathy are visible. The measurements were performed by the Jena Fluorescence Lifetime Laser Scanner Ophthalmoscope applying time-correlated single photon counting (TCSPC) in two spectral channels (K1: 490-560 nm, K2:560-700ps). The fluorescence was excited by 70 ps pulses (FWHM) at 448 nm. The decay of fluorescence intensity was triple-exponentially approximated. The frequency of amplitudes, lifetimes, and relative contributions was compared in fields of the same size and position in healthy subjects and in diabetic patients. The most sensitive parameter was the lifetime T2 in the short-wavelength channel, which corresponds to the neuronal retina. The changes in lifetime point to a loss of free NADH and an increased contribution of protein-bound NADH in the pre-stage of diabetic retinopathy.

Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina

International Nuclear Information System (INIS)

Maebayashi, Hisae; Takeuchi, Shigako; Masuda, Chiaki; Makino, Satoshi; Fukui, Kenji; Kimura, Hiroshi; Tooyama, Ikuo

2012-01-01

The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer

Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy.

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Michael Anthony Ruiz

Full Text Available Glucose-induced augmented vascular endothelial growth factor (VEGF production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2, has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation and that inhibition of PRC2 increases miR-200b while reducing VEGF. Furthermore, retinal tissue from animal models of diabetes showed increased expression of major PRC2 components, demonstrating in vivo relevance. This research established a repressive relationship between PRC2 and miR-200b, providing evidence of a novel mechanism of miRNA regulation through histone methylation.

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

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Ramon Coral Ghanem

2004-06-01

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

Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

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Funari, Vincent A; Winkler, Michael; Brown, Jordan; Dimitrijevich, Slobodan D; Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

2013-01-01

MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6) and diabetic (n=6) central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR) and by in situ hybridization (ISH) in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR) or their inhibitors (antagomirs) using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

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Vincent A Funari

Full Text Available MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6 and diabetic (n=6 central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR and by in situ hybridization (ISH in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR or their inhibitors (antagomirs using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

Rhythmic ganglion cell activity in bleached and blind adult mouse retinas.

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Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

2014-01-01

In retinitis pigmentosa--a degenerative disease which often leads to incurable blindness--the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor's dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the understanding of the degeneration process and may guide future rescue strategies.

Effect of PKCbeta on retinal oxygenation response in experimental diabetes.

OpenAIRE

Luan, H.; Leitges, M.; Gupta, R.; Pacheco, D.; Seidner, A.; Liggett, J.; Ito, Y.; Kowluru, R.; Berkowitz, B.

2004-01-01

PURPOSE: To test the hypotheses that, in mice, breathing carbogen (95% O(2)-5% CO(2)) oxygenates the retina better than breathing 100% oxygen, the superior hemiretinal oxygenation response to carbogen inhalation is subnormal early in diabetes, and diabetes-induced elevation of retinal protein kinase C (PKC)-beta contributes to this pathophysiology. METHODS: Retinal oxygenation response (DeltaPO(2)) was measured using functional magnetic resonance imaging (MRI) and either carbogen or 100% oxyg...

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

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Xiao, Zhitao; Zhang, Xinpeng; Geng, Lei; Zhang, Fang; Wu, Jun; Tong, Jun; Ogunbona, Philip O; Shan, Chunyan

2017-10-26

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Identification of StARD3 as a lutein-binding protein in the macula of the primate retina.

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Li, Binxing; Vachali, Preejith; Frederick, Jeanne M; Bernstein, Paul S

2011-04-05

Lutein, zeaxanthin, and their metabolites are the xanthophyll carotenoids that form the macular pigment of the human retina. Epidemiological evidence suggests that high levels of these carotenoids in the diet, serum, and macula are associated with a decreased risk of age-related macular degeneration (AMD), and the AREDS2 study is prospectively testing this hypothesis. Understanding the biochemical mechanisms underlying the selective uptakes of lutein and zeaxanthin into the human macula may provide important insights into the physiology of the human macula in health and disease. GSTP1 is the macular zeaxanthin-binding protein, but the identity of the human macular lutein-binding protein has remained elusive. Prior identification of the silkworm lutein-binding protein (CBP) as a member of the steroidogenic acute regulatory domain (StARD) protein family and selective labeling of monkey photoreceptor inner segments with an anti-CBP antibody provided an important clue for identifying the primate retina lutein-binding protein. The homology of CBP with all 15 human StARD proteins was analyzed using database searches, Western blotting, and immunohistochemistry, and we here provide evidence to identify StARD3 (also known as MLN64) as a human retinal lutein-binding protein. Antibody to StARD3, N-62 StAR, localizes to all neurons of monkey macular retina and especially cone inner segments and axons, but does not colocalize with the Müller cell marker, glutamine synthetase. Further, recombinant StARD3 selectively binds lutein with high affinity (K(D) = 0.45 μM) when assessed by surface plasmon resonance (SPR) binding assays. Our results demonstrate previously unrecognized, specific interactions of StARD3 with lutein and provide novel avenues for exploring its roles in human macular physiology and disease.

[Degenerative lesions of the peripheral retina].

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Conart, J-B; Baron, D; Berrod, J-P

2014-01-01

Degenerative lesions of the peripheral retina are present from teenage years onwards and increase with age. These abnormabilities are frequent, some of them being benign while others predispose to retinal tears and detachment. In the latter case, the lesions are rhegmatogenous and may justify prophylactic treatment by laser photocoagulation. We distinguish congenital lesions of the peripheral retina and intraretinal, chorioretinal and vitreoretinal degenerations. The holes and tears observed in 2% of the population consist of round atrophic holes, "horseshoe" tears, oral dialyses and giant tears. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Diabetes Accelerates Retinal Neuronal Cell Death In A Mouse Model of Endogenous Hyperhomocysteinemia

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Preethi S. Ganapathy

2009-07-01

Full Text Available Hyperhomocysteinemia has been implicated in visual dysfunction. We reported recently that mice with endogenous hyperhomocysteinemia, due to mutation of the cystathionine-β-synthase (cbs gene, demonstrate loss of neurons in the retinal ganglion cell (RGC layer and other retinal layers as homocysteine levels increase. Some clinical studies implicate hyperhomocysteinemia in the pathogenesis of diabetic retinopathy, which is also characterized by RGC loss. The present study used cbs+/- mice to determine whether modest elevation of plasma homocysteine, in the presence of diabetes, accelerates neuronal cell loss. Diabetes (DB was induced in 3 wk old cbs+/- and wildtype mice using streptozotocin; four groups of mice were studied: DB cbs+/-; non-DB cbs+/-; DB cbs+/+; non-DB cbs+/+. One group of diabetic cbs+/- mice was maintained on a high methionine diet (HMD, 0.5% methionine drinking water to increase plasma homocysteine slightly. Eyes were harvested at 5, 10 and 15 weeks post-onset of diabetes; retinal cryosections were examined by light microscopy and subjected to systematic morphometric analysis. Diabetic cbs+/- had significantly fewer RGCs at 5 weeks compared to age-matched, non-diabetic cbs+/- and wildtype controls (10.0 ± 0.5 versus 14.9 ± 0.5 and 15.8 ± 0.6 cells/100 µm retina length, respectively. Significant differences in retinas of DB/high homocysteine versus controls were obtained 15 wks post-onset of diabetes including fewer RGCS and decreased thickness of inner nuclear and plexiform layers. Moderate increases in plasma homocysteine coupled with diabetes cause a more dramatic alteration of retinal phenotype than elevated homocysteine or diabetes alone and suggest that diabetes accelerates the retinal neuronal death in hyperhomocysteinemic mice.

β2-Adrenergic Receptor Knockout Mice Exhibit A Diabetic Retinopathy Phenotype

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Jiang, Youde; Zhang, Qiuhua; Liu, Li; Tang, Jie; Kern, Timothy S.; Steinle, Jena J.

2013-01-01

There is considerable evidence from our lab and others for a functional link between β-adrenergic receptor and insulin receptor signaling pathways in retina. Furthermore, we hypothesize that this link may contribute to lesions similar to diabetic retinopathy in that the loss of adrenergic input observed in diabetic retinopathy may disrupt normal anti-apoptotic insulin signaling, leading to retinal cell death. Our studies included assessment of neural retina function (ERG), vascular degeneration, and Müller glial cells (which express only β1 and β2-adrenergic receptor subtypes). In the current study, we produced β2-adrenergic receptor knockout mice to examine this deletion on retinal neurons and vasculature, and to identify specific pathways through which β2-adrenergic receptor modulates insulin signaling. As predicted from our hypothesis, β2-adrenergic receptor knockout mice display certain features similar to diabetic retinopathy. In addition, loss of β2-adrenergic input resulted in an increase in TNFα, a key inhibitor of insulin receptor signaling. Increased TNFα may be associated with insulin-dependent production of the anti-apoptotic factor, Akt. Since the effects occurred in vivo under normal glucose conditions, we postulate that aspects of the diabetic retinopathy phenotype might be triggered by loss of β2-adrenergic receptor signaling. PMID:23894672

Functions of Müller cell-derived vascular endothelial growthfactor in diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

2015-01-01

Müller cells are macroglia and play many essentialroles as supporting cells in the retina. To respond topathological changes in diabetic retinopathy （DR）, amajor complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascularendothelial growth factor （VEGF or VEGF-A）. As VEGFis expressed by multiple retinal cell-types and Müllerglia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function ofVEGF or other globally expressed proteins produced byMüller cells. With the development of conditional genetargeting tools, it is now possible to dissect the functionof Müller cell-derived VEGF in vivo . By using conditionalgene targeting approach, we demonstrate that Müllerglia are a major source of retinal VEGF in diabetic miceand Müller cell-derived VEGF plays a significant role inthe alteration of protein expression and peroxynitration,which leads to retinal inflammation, neovascularization,vascular leakage, and vascular lesion, key pathologicalchanges in DR. Therefore, Müller glia are a potentialcellular target for the treatment of DR, a leading causeof blindness.

FPGA-Based Real Time, Multichannel Emulated-Digital Retina Model Implementation

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Zsolt Vörösházi

2009-01-01

Full Text Available The function of the low-level image processing that takes place in the biological retina is to compress only the relevant visual information to a manageable size. The behavior of the layers and different channels of the neuromorphic retina has been successfully modeled by cellular neural/nonlinear networks (CNNs. In this paper, we present an extended, application-specific emulated-digital CNN-universal machine (UM architecture to compute the complex dynamic of this mammalian retina in video real time. The proposed emulated-digital implementation of multichannel retina model is compared to the previously developed models from three key aspects, which are processing speed, number of physical cells, and accuracy. Our primary aim was to build up a simple, real-time test environment with camera input and display output in order to mimic the behavior of retina model implementation on emulated digital CNN by using low-cost, moderate-sized field-programmable gate array (FPGA architectures.

The Diabetes Pearl: Diabetes biobanking in The Netherlands

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van’t Riet Esther

2012-11-01

Full Text Available Abstract Background Type 2 diabetes is associated with considerable comorbidity and severe complications, which reduce quality of life of the patients and require high levels of healthcare. The Diabetes Pearl is a large cohort of patients diagnosed with type 2 diabetes, covering different geographical areas in the Netherlands. The aim of the study is to create a research infrastructure that will allow the study of risk factors, including biomarkers and genetic determinants for severe diabetes complications. Methods/design Baseline examinations began November 2009 and will continue through 2012. By the end of 2012, it is expected that 7000 patients with type 2 diabetes will be included in the Diabetes Pearl cohort. To ensure quality of the data collected, standard operation procedures were developed and used in all 8 recruitment centers. From all patients who provide informed consent, the following information is collected: personal information, medication use, physical examination (antropometry, blood pressure, electrocardiography (ECG, retina photographs, ankle-brachial index, peripheral vibration perception, self-report questionnaire (socio-economic status, lifestyle, (family history of disease, and psychosocial well-being, laboratory measurements (glucose, A1c, lipid profile, kidney function, biobank material (storage of urine and blood samples and isolated DNA. All gathered clinical data and biobank information is uploaded to a database for storage on a national level. Biobanks are maintained locally at all recruitment centers. Discussion The Diabetes Pearl is large-scale cohort of type 2 diabetes patients in the Netherlands aiming to study risk factors, including biomarkers and genetic markers, for disease deterioration and the development of severe diabetes complications. As a result of the well-designed research design and the national coverage, the Diabetes Pearl data can be of great value to national and international researchers with

A Computational Model of Peripheral Photocoagulation for the Prevention of Progressive Diabetic Capillary Occlusion

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Thomas J. Gast

2016-01-01

Full Text Available We developed a computational model of the propagation of retinal ischemia in diabetic retinopathy and analyzed the consequences of various patterns and sizes of burns in peripheral retinal photocoagulation. The model addresses retinal ischemia as a phenomenon of adverse local feedback in which once a capillary is occluded there is an elevated probability of occlusion of adjacent capillaries resulting in enlarging areas of retinal ischemia as is commonly seen clinically. Retinal burns of different sizes and patterns, treated as local oxygen sources, are predicted to have different effects on the propagation of retinal ischemia. The patterns of retinal burns are optimized with regard to minimization of the sum of the photocoagulated retina and computer predicted ischemic retina. Our simulations show that certain patterns of retinal burns are effective at preventing the spatial spread of ischemia by creating oxygenated boundaries across which the ischemia does not propagate. This model makes no statement about current PRP treatment of avascular peripheral retina and notes that the usual spot sizes used in PRP will not prevent ischemic propagation in still vascularized retinal areas. The model seems to show that a properly patterned laser treatment of still vascularized peripheral retina may be able to prevent or at least constrain the propagation of diabetic retinal ischemia in those retinal areas with intact capillaries.

Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: potential role for CTGF in human diabetic foot ulcer healing.

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Henshaw, F R; Boughton, P; Lo, L; McLennan, S V; Twigg, S M

2015-01-01

Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P diabetic foot ulcers.

The mammalian retina as a clock

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Tosini, Gianluca; Fukuhara, Chiaki

2002-01-01

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

Selective retina therapy (SRT)

International Nuclear Information System (INIS)

Brinkmann, R.; Birngruber, R.

2007-01-01

Selective Retina Therapy (SRT) is a new and very gentle laser method developed at the Medical Laser Center Luebeck. It is currently investigated clinically in order to treat retinal disorders associated with a decreased function of the retinal pigment epithelium (RPE). SRT is designed to selectively effect the RPE while sparing the neural retina and the photoreceptors as well as the choroid. Aim of the therapy is the rejuvenation of the RPE in the treated areas, which should ideally lead to a long term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with a complete thermal necrosis of the treated site, SRT completely retains full vision. This paper reviews the methods and mechanisms behind selective RPE effects and reports the first clinical results. An online dosimetry technique to visualize the ophthalmoscopically invisible effects is introduced. (orig.)

Developmentally Regulated Production of meso-Zeaxanthin in Chicken Retinal Pigment Epithelium/Choroid and Retina.

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Gorusupudi, Aruna; Shyam, Rajalekshmy; Li, Binxing; Vachali, Preejith; Subhani, Yumna K; Nelson, Kelly; Bernstein, Paul S

2016-04-01

meso-Zeaxanthin is a carotenoid that is rarely encountered in nature outside of the vertebrate eye. It is not a constituent of a normal human diet, yet this carotenoid comprises one-third of the primate macular pigment. In the current study, we undertook a systematic approach to biochemically characterize the production of meso-zeaxanthin in the vertebrate eye. Fertilized White Leghorn chicken eggs were analyzed for the presence of carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid were isolated, and carotenoids were extracted. The samples were analyzed on C-30 or chiral HPLC columns to determine the carotenoid composition. Lutein and zeaxanthin were found in all studied nonocular tissues, but no meso-zeaxanthin was ever detected. Among the ocular tissues, the presence of meso-zeaxanthin was consistently observed starting at embryonic day 17 (E17) in the RPE/choroid, several days before its consistent detection in the retina. If RPE/choroid of an embryo was devoid of meso-zeaxanthin, the corresponding retina was always negative as well. This is the first report of developmentally regulated synthesis of meso-zeaxanthin in a vertebrate system. Our observations suggest that the RPE/choroid is the primary site of meso-zeaxanthin synthesis. Identification of meso-zeaxanthin isomerase enzyme in the developing chicken embryo will facilitate our ability to determine the biochemical mechanisms responsible for production of this unique carotenoid in other higher vertebrates, such as humans.

A Retina-Like Dual Band Organic Photosensor Array for Filter-Free Near-Infrared-to-Memory Operations.

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Wang, Hanlin; Liu, Hongtao; Zhao, Qiang; Ni, Zhenjie; Zou, Ye; Yang, Jie; Wang, Lifeng; Sun, Yanqiu; Guo, Yunlong; Hu, Wenping; Liu, Yunqi

2017-08-01

Human eyes use retina photoreceptor cells to absorb and distinguish photons from different wavelengths to construct an image. Mimicry of such a process and extension of its spectral response into the near-infrared (NIR) is indispensable for night surveillance, retinal prosthetics, and medical imaging applications. Currently, NIR organic photosensors demand optical filters to reduce visible interference, thus making filter-free and anti-visible NIR imaging a challenging task. To solve this limitation, a filter-free and conformal, retina-inspired NIR organic photosensor is presented. Featuring an integration of photosensing and floating-gate memory modules, the device possesses an acute color distinguishing capability. In general, the retina-like photosensor transduces NIR (850 nm) into nonvolatile memory and acts as a dynamic photoswitch under green light (550 nm). In doing this, a filter-free but color-distinguishing photosensor is demonstrated that selectively converts NIR optical signals into nonvolatile memory. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Loss of Melanopsin-Expressing Retinal Ganglion Cells in Patients With Diabetic Retinopathy

DEFF Research Database (Denmark)

Obara, Elisabeth Anne; Hannibal, Jens; Heegaard, Steffen

2017-01-01

Purpose: Photo-entrainment of the circadian clock is mediated by melanopsin-expressing retinal ganglion cells (mRGCs) located in the retina. Patients suffering from diabetic retinopathy (DR) show impairment of light regulated circadian activity such as sleep disorders, altered blood pressure...

Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans.

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Satoshi Hara

Full Text Available Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3 gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI with advanced glycation end-product (AGE and Nε-carboxymethyl-lysine (CML deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

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Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

2012-01-01

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water

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

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

2016-04-01

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

Effects of nuclear factor κB expression on retinal neovascularization and apoptosis in a diabetic retinopathy rat model

Institute of Scientific and Technical Information of China (English)

Ning; Jiang; Xiao-Long; Chen; Hong-Wei; Yang; Yu-Ru; Ma

2015-01-01

AIM: To investigate the expression and role of nuclear factor κB(NF-κB) in diabetic retinopathy(DR) and its relationship with neovascularization and retinal cell apoptosis. METHODS: A total of 80 male Wistar rats were randomly assigned to control(4, 8, 12 and 16 wk, n =10 in each group) and diabetes mellitus(DM) groups(4, 8, 12 and 16wk, n =10 in each group). A diabetic rat model was established by intraperitoneal injection of streptozotocin(60 mg/kg). After 4, 8, 12 and 16 wk, rats were sacrificed.Retinal layers and retinal neovascularization growth were stained with hematoxylin-eosin and examined under light microscopy. Cell apoptosis in the retina was detected by Td T-mediated d UTP nick end labeling, and NF-κB distribution and expression in the retina was determined using immunohistochemistry. RESULTS: DM model success rate up to 100%.Diabetes model at each time point after the experimental groupcompared with the control group, the blood glucose was significantly increased, decreased body weight, each time point showed significant differences compared with the control group(P <0.01). After 12 wk other pathological changes in the retina of diabetic rats were observed; after 16 wk, neovascularization were observed. After 1mo, retinal cell apoptosis was observed.Compared with the control group, NF-κB expression in the DM group significantly increased with disease duration.CONCLUSION: With the prolonging of DM progression,the expression NF-κB increases. NF-κB may be related to retinal cell apoptosis and neovascularization.

Inhibition of HIF-1α decreases expression of pro-inflammatory IL-6 and TNF-α in diabetic retinopathy.

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Gao, Xiuhua; Li, Yonghua; Wang, Hongxia; Li, Chuanbao; Ding, Jianguang

2017-12-01

Recent studies demonstrate that pro-inflammatory cytokines (PICs, i.e. IL-1β, IL-6 and TNF-α) in retinal tissues are likely involved in the development of diabetic retinopathy (DR). In this report, we particularly examined contributions of hypoxia inducible factor subtype 1α (HIF-1α) to the expression of PICs and their receptors in diabetic retina. Streptozotocin (STZ) was systemically injected to induce hyperglycaemia in rats. ELISA and Western blot analysis were employed to determine the levels of HIF-1α and PICs as well as PIC receptors in retinal tissues of control rats and STZ rats. The levels of retinal HIF-1α were significantly increased in STZ rats 4-10 weeks after induction of hyperglycaemia as compared with control animals. With increasing HIF-1α retinal PICs including IL-1β, IL-6 and TNF-α, their respective receptors, namely IL-1R, IL-6R and TNFR1, were also elevated in STZ rats. Moreover, inhibition of HIF-1α by injection of 2-methoxyestradiol (2-MET) significantly decreased the amplified expression IL-6, TNF-α, IL-6R and TNFR1 in diabetic retina, but did not modify IL-1β pathway. In addition, we examined protein expression of Caspase-3 indicating cell apoptosis in the retina of STZ rats after infusing 2-MET, demonstrating that 2-MET attenuated an increase in Caspase-3 evoked by STZ. Hypoxia inducible factor subtype 1α (HIF-1α) activated in diabetic retina is likely to play a role in regulating pathophysiological process via IL-6 and TNF-α mechanism. This has pharmacological implications to target specific HIF-1α, IL-6 and TNF-α signalling pathway for dysfunction and vulnerability related to DR. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Retina tissue engineering by conjunctiva mesenchymal stem cells encapsulated in fibrin gel: Hypotheses on novel approach to retinal diseases treatment.

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Soleimannejad, Mostafa; Ebrahimi-Barough, Somayeh; Nadri, Samad; Riazi-Esfahani, Mohammad; Soleimani, Masoud; Tavangar, Seyed Mohammad; Ai, Jafar

2017-04-01

Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision. Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders. In this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells. Application of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy

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Tingting Jiang

2016-01-01

Full Text Available Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR. Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p. injection of STZ (60 mg/kg in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p. was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL. Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS, was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina.

Expression of nitric oxide synthase during the development of RCS rat retinas.

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Sharma, R K; Warfvinge, K; Ehinger, B

2001-01-01

Nitric oxide (NO) has been reported to be both neurodestructive and neuroprotective in the central nervous system and could possibly play an important role in neurodegenerative disorders. On the assumption that NO synthesis may influence degenerative processes in the retina, we have examined the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive cells in developing Royal College of Surgeons (RCS) rat retinas, which is an animal model for retinal degeneration. An antibody against constitutive neuronal NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days 3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days 3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas but were distinctly seen in the PN 7 retina along with a plexus in the inner plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of the plexus in the inner plexiform layer could be seen at PN 10, which became more distinct at PN 14. The immunoreactive cells were detected also in the oldest retina examined, which was PN 281 in the case of RCS rats. In both groups, certain amacrine cells, certain bipolar cells and certain horizontal cells were found to be immunoreactive. In conclusion, the developmental timetable of the NOS immunoreactivity was identical in the normal and the RCS rat retinas. The NOS-immunoreactive cells persisted in the RCS retinas even when the retina had degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot be ruled out from this study. We conclude that the chronological and qualitative development of the constitutive neuronal NOS immunoreactivity is normal in RCS rat retinas. Copyright 2001 S. Karger AG, Basel

Minireview: Epigenetics of obesity and diabetes in humans.

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Slomko, Howard; Heo, Hye J; Einstein, Francine H

2012-03-01

Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation.

Comparative Aspects of Human, Canine, and Feline Obesity and Factors Predicting Progression to Diabetes

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Margarethe Hoenig

2014-08-01

Full Text Available Obesity and diabetes mellitus are common diseases in humans, dogs and cats and their prevalence is increasing. Obesity has been clearly identified as a risk factor for type 2 diabetes in humans and cats but recent data are missing in dogs, although there is evidence that the unprecedented rise in canine obesity in the last decade has led to a rise in canine diabetes of similar magnitude. The insulin resistance of obesity has often been portrayed as major culprit in the loss of glucose control; however, insulin resistance alone is not a good indicator of progression to diabetes in people or pets. A loss of beta cell function is necessary to provide the link to impaired fasting and post-prandial plasma glucose. Increased endogenous glucose output by the liver is also a prerequisite for the increase in fasting blood glucose when non-diabetic obese humans and pets develop diabetes. This may be due to decreased hepatic insulin sensitivity, decreased insulin concentrations, or a combination of both. While inflammation is a major link between obesity and diabetes in humans, there is little evidence that a similar phenomenon exists in cats. In dogs, more studies are needed to examine this important issue.

X-ray microprobe analysis of the retina and RPE in sheep with ovine ceroid-lipofuscinosis

International Nuclear Information System (INIS)

Samuelson, D.A.; Armstrong, D.; Jolly, R.

1990-01-01

Ovine ceroid-lipofuscinosis (OCL) is one animal model for the human condition, and because autofluorescent lipopigments are prominent in the brain and eye, it may also prove useful as a model for aging. For example, a progressive decline in electrical recording from brain and retina are observed in both aging and OCL. Samples of retinal and retinal pigment epithelial (RPE) tissues were obtained from a young control. 2 animals with OCL and a normal aged sheep. Specimens were cryo-fractured and examined by scanning electron microscopy/x-ray microanalysis. Measurements made of 6 individual cells in the ganglion layer of OCL specimens, the remainder of the retina, and RPE showed age-related changes in zinc, iron, and copper which were associated with lipopigment accumulation in the RPE. There was marked decrease in phosphate, sulfur, and manganese levels, as photoreceptor cells and their outer segments are lost in the disease process. This is the first report of metal analysis in the retina and RPE in a disease entity, and as a function of normal aging

The elementary representation of spatial and color vision in the human retina.

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Sabesan, Ramkumar; Schmidt, Brian P; Tuten, William S; Roorda, Austin

2016-09-01

The retina is the most accessible element of the central nervous system for linking behavior to the activity of isolated neurons. We unraveled behavior at the elementary level of single input units-the visual sensation generated by stimulating individual long (L), middle (M), and short (S) wavelength-sensitive cones with light. Spectrally identified cones near the fovea of human observers were targeted with small spots of light, and the type, proportion, and repeatability of the elicited sensations were recorded. Two distinct populations of cones were observed: a smaller group predominantly associated with signaling chromatic sensations and a second, more numerous population linked to achromatic percepts. Red and green sensations were mainly driven by L- and M-cones, respectively, although both cone types elicited achromatic percepts. Sensations generated by cones were rarely stochastic; rather, they were consistent over many months and were dominated by one specific perceptual category. Cones lying in the midst of a pure spectrally opponent neighborhood, an arrangement purported to be most efficient in producing chromatic signals in downstream neurons, were no more likely to signal chromatic percepts. Overall, the results are consistent with the idea that the nervous system encodes high-resolution achromatic information and lower-resolution color signals in separate pathways that emerge as early as the first synapse. The lower proportion of cones eliciting color sensations may reflect a lack of evolutionary pressure for the chromatic system to be as fine-grained as the high-acuity achromatic system.

Real-time simulation of the retina allowing visualization of each processing stage

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Teeters, Jeffrey L.; Werblin, Frank S.

1991-08-01

The retina computes to let us see, but can we see the retina compute? Until now, the answer has been no, because the unconscious nature of the processing hides it from our view. Here the authors describe a method of seeing computations performed throughout the retina. This is achieved by using neurophysiological data to construct a model of the retina, and using a special-purpose image processing computer (PIPE) to implement the model in real time. Processing in the model is organized into stages corresponding to computations performed by each retinal cell type. The final stage is the transient (change detecting) ganglion cell. A CCD camera forms the input image, and the activity of a selected retinal cell type is the output which is displayed on a TV monitor. By changing the retina cell driving the monitor, the progressive transformations of the image by the retina can be observed. These simulations demonstrate the ubiquitous presence of temporal and spatial variations in the patterns of activity generated by the retina which are fed into the brain. The dynamical aspects make these patterns very different from those generated by the common DOG (Difference of Gaussian) model of receptive field. Because the retina is so successful in biological vision systems, the processing described here may be useful in machine vision.

Automatic diabetic retinopathy classification

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Bravo, María. A.; Arbeláez, Pablo A.

2017-11-01

Diabetic retinopathy (DR) is a disease in which the retina is damaged due to augmentation in the blood pressure of small vessels. DR is the major cause of blindness for diabetics. It has been shown that early diagnosis can play a major role in prevention of visual loss and blindness. This work proposes a computer based approach for the detection of DR in back-of-the-eye images based on the use of convolutional neural networks (CNNs). Our CNN uses deep architectures to classify Back-of-the-eye Retinal Photographs (BRP) in 5 stages of DR. Our method combines several preprocessing images of BRP to obtain an ACA score of 50.5%. Furthermore, we explore subproblems by training a larger CNN of our main classification task.

Functional Architecture of the Retina: Development and Disease

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

2014-01-01

Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina. PMID:24984227

Human embryonic stem cell-derived pancreatic endoderm alleviates diabetic pathology and improves reproductive outcome in C57BL/KsJ-Lep(db/+) gestational diabetes mellitus mice.

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Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

2015-07-01

Gestational diabetes mellitus is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal maldevelopment. The cause of gestational diabetes mellitus can be attributed to both genetic and environmental factors, hence complicating its diagnosis and treatment. Pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice. In this study, we have developed a system of treating diabetes using human embryonic stem cell-derived pancreatic endoderm in a mouse model of gestational diabetes mellitus. Human embryonic stem cells were differentiated in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus. The transplant greatly improved glucose metabolism and reproductive outcome of the females compared with the control groups. Our findings support the feasibility of using differentiated human embryonic stem cells for treating gestational diabetes mellitus patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Modeling laser damage to the retina

Science.gov (United States)

Clark, Clifton D.

This dissertation presents recent progress in several areas related to modeling laser damage to the retina. In Chapter 3, we consider the consequences of using the Arrhenius damage model to predict the damage thresholds of multiple pulse, or repetitive pulse, exposures. We have identified a few fundamental trends associated with the multiple pulse damage predictions made by the Arrhenius model. These trends differ from what would be expected by non-thermal mechanisms, and could prove useful in differentiating thermal and non-thermal damage. Chapter 4 presents a new rate equation damage model hypothesized to describe photochemical damage. The model adds a temperature dependent term to the simple rate equation implied by the principle of reciprocity that is characteristic of photochemical damage thresholds. A recent damage threshold study, conducted in-vitro, has revealed a very sharp transition between thermal and photochemical damage threshold trends. For the wavelength used in the experiment (413 nm), thermal damage thresholds were observed at exposure levels that were twice the expected photochemical damage threshold, based on the traditional understanding of photochemical damage. Our model accounts for this observed trend by introducing a temperature dependent quenching, or repair, rate to the photochemical damage rate. For long exposures that give a very small temperature rise, the model reduces to the principle of reciprocity. Near the transition region between thermal and photochemical damage, the model allows the damage threshold to be set by thermal mechanisms, even at exposure above the reciprocity exposure. In Chapter 5, we describe a retina damage model that includes thermal lensing in the eye by coupling beam propagation and heat transfer models together. Thermal lensing has recently been suggested as a contributing factor to the large increase in measured retinal damage thresholds in the near infrared. The transmission of the vitreous decreases

Diabetes Accelerates Retinal neuronal cell Death in A Mouse Model of endogenous Hyperhomocysteinemia

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Preethi S. Ganapathy

2009-01-01

Full Text Available Hyperhomocysteinemia has been implicated in visual dysfunction. We reported recently that mice with endogenous hyperhomocysteinemia, due to mutation of the cystathionine-β-synthase ( cbs gene, demonstrate loss of neurons in the retinal ganglion cell (RGC layer and other retinal layers as homocysteine levels increase. Some clinical studies implicate hyperhomocysteinemia in the pathogenesis of diabetic retinopathy, which is also characterized by RGC loss. The present study used cbs +/– mice to determine whether modest elevation of plasma homocysteine, in the presence of diabetes, accelerates neuronal cell loss. Diabetes (DB was induced in 3 wk old cbs +/– and wildtype mice using streptozotocin; four groups of mice were studied: DB cbs +/– non-DB cbs +/– DB cbs +/+ ; non-DB cbs +/+ . One group of diabetic cbs +/– mice was maintained on a high methionine diet (HMD, 0.5% methionine drinking water to increase plasma homocysteine slightly. Eyes were harvested at 5, 10 and 15 weeks post-onset of diabetes; retinal cryosections were examined by light microscopy and subjected to systematic morphometric analysis. Diabetic cbs +/– had significantly fewer RGCs at 5 weeks compared to age-matched, non-diabetic cbs +/– and wildtype controls (10.0 ± 0.5 versus 14.9 ± 0.5 and 15.8 ± 0.6 cells/100 μm retina length, respectively. Significant differences in retinas of DB/high homocysteine versus controls were obtained 15 wks post-onset of diabetes including fewer RGCS and decreased thickness of inner nuclear and plexiform layers. Moderate increases in plasma homocysteine coupled with diabetes cause a more dramatic alteration of retinal phenotype than elevated homocysteine or diabetes alone and suggest that diabetes accelerates the retinal neuronal death in hyperhomocysteinemic mice.

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

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

2016-01-01

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

Illumination-invariant face recognition with a contrast sensitive silicon retina

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

1993-11-29

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

Maturação funcional da retina em bebês prematuros

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Adriana Berezovsky

2007-06-01

Full Text Available A retina humana ainda não está totalmente desenvolvida no nascimento. Só após o nascimento é que ocorrem mudanças anatômicas como o aumento na densidade de cones centrais e o alongamento do segmento externo dos fotorreceptores. As mudanças funcionais que ocorrem na retina com a maturação no primeiro ano de vida podem ser avaliadas pela técnica do eletrorretinograma de campo total, que representa a atividade somada da retina distal em resposta à luz. Abordaremos aspectos da maturação funcional da retina avaliada pelo eletrorretinograma em bebês prematuros.

Functional imaging of hemodynamic stimulus response in the rat retina with ultrahigh-speed spectral / Fourier domain OCT

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Choi, WooJhon; Baumann, Bernhard; Clermont, Allen C.; Feener, Edward P.; Boas, David A.; Fujimoto, James G.

2013-03-01

Measuring retinal hemodynamics in response to flicker stimulus is important for investigating pathophysiology in small animal models of diabetic retinopathy, because a reduction in the hyperemic response is thought to be one of the earliest changes in diabetic retinopathy. In this study, we investigated functional imaging of retinal hemodynamics in response to flicker stimulus in the rat retina using an ultrahigh speed spectral / Fourier domain OCT system at 840nm with an axial scan rate of 244kHz. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was +/-37.7mm/s. Pulsatile total retinal arterial blood flow as a function of time was measured using an en face Doppler approach where a 200μm × 200μm area centered at the central retinal artery was repeatedly raster scanned at a volume acquisition rate of 55Hz. Three-dimensional capillary imaging was performed using speckle decorrelation which has minimal angle dependency compared to other angiography techniques based on OCT phase information. During OCT imaging, a flicker stimulus could be applied to the retina synchronously by inserting a dichroic mirror in the imaging interface. An acute transient increase in total retinal blood flow could be detected. At the capillary level, an increase in the degree of speckle decorrelation in capillary OCT angiography images could also be observed, which indicates an increase in the velocity of blood at the capillary level. This method promises to be useful for the investigation of small animal models of ocular diseases.

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications

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Thomas Schwitzer

2016-01-01

Full Text Available Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.

MEMS scanner mirror based system for retina scanning and in eye projection

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Woittennek, Franziska; Knobbe, Jens; Pügner, Tino; Dallmann, Hans-Georg; Schelinski, Uwe; Grüger, Heinrich

2015-02-01

Many applications could benefit from miniaturized systems to scan blood vessels behind the retina in the human eye, so called "retina scanning". This reaches from access control to sophisticated security applications and medical devices. High volume systems for consumer applications require low cost and a user friendly operation. For example this includes no need for removal of glasses and self-adjustment, in turn guidance of focus and point of attraction by simultaneous projection for the user. A new system has been designed based on the well-known resonantly driven 2-d scanner mirror of Fraunhofer IPMS. A combined NIR and VIS laser system illuminates the eye through an eye piece designed for an operating distance allowing the use of glasses and granting sufficient field of view. This usability feature was considered to be more important than highest miniaturization. The modulated VIS laser facilitates the projection of an image directly onto the retina. The backscattered light from the continuous NIR laser contains the information of the blood vessels and is detected by a highly sensitive photo diode. A demonstrational setup has been realized including readout and driving electronics. The laser power was adjusted to an eye-secure level. Additional security features were integrated. Test measurements revealed promising results. In a first demonstration application the detection of biometric pattern of the blood vessels was evaluated for issues authentication in.

Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity.

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Fu, Zhiyao; Berhane, Feven; Fite, Alemu; Seyoum, Berhane; Abou-Samra, Abdul B; Zhang, Ren

2014-05-23

Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic β-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N=15) or diabetic (BMI- and age-matched; N=14); b) lean or obese (N=53 totally) and c) fasting and 2 hours following a defined meal (N=12). Serum lipasin levels were determined by the enzyme-linked immunosorbent assay. Lipasin levels [mean±SEM] were increased by more than two fold (Plipasin levels were positively correlated with BMI (rho=0.49, Plipasin/betatrophin is nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity.

Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model

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Zhao, Yong, E-mail: yongzhao@uic.edu [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Guo, Chengshan; Hwang, David; Lin, Brian; Dingeldein, Michael; Mihailescu, Dan; Sam, Susan; Sidhwani, Seema [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Zhang, Yongkang [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Jain, Sumit [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Skidgel, Randal A. [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Prabhakar, Bellur S. [Department of Immunology and Microbiology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Mazzone, Theodore [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Holterman, Mark J. [Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612 (United States)

2010-09-03

Research highlights: {yields} Establish a human immune-mediated type 1 diabetic model in NOD-scid IL2r{gamma}{sup null} mice. {yields} Using the irradiated diabetic NOD mouse spleen mononuclear cells as trigger. {yields} The islet {beta} cells were selectively destroyed by infiltrated human T cells. {yields} The model can facilitate translational research to find a cure for type 1 diabetes. -- Abstract: Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing {beta} cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2r{gamma}{sup null} mice. The selective destruction of pancreatic islet {beta} cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total {beta}-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the {beta} cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet {beta} cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4{sup +} T cell infiltration and clonal expansion, and the mouse islet {beta}-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet {beta} cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.

Relations between Cardiac and Visual Phenotypes in Diabetes: A Multivariate Approach.

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Oliveiros, Bárbara; Sanches, Mafalda; Quendera, Bruno; Graça, Bruno; Guelho, Daniela; Gomes, Leonor; Carrilho, Francisco; Caseiro-Alves, Filipe; Castelo-Branco, Miguel

2016-01-01

Cardiovascular disease and diabetes represent a major public health concern. The former is the most frequent cause of death and disability in patients with type 2 diabetes, where left ventricular dysfunction is highly prevalent. Moreover, diabetic retinopathy is becoming a dominant cause of visual impairment and blindness. The complex relation between cardiovascular disease and diabetic retinopathy as a function of ageing, obesity and hypertension remains to be clarified. Here, we investigated such relations in patients with diabetes type 2, in subjects with neither overt heart disease nor advanced proliferative diabetic retinopathy. We studied 47 patients and 50 controls, aged between 45 and 65 years, equally distributed according to gender. From the 36 measures regarding visual structure and function, and the 11 measures concerning left ventricle function, we performed data reduction to obtain eight new derived variables, seven of which related to the eye, adjusted for age, gender, body mass index and high blood pressure using both discriminant analysis (DA) and logistic regression (LR). We found moderate to strong correlation between left ventricle function and the eye constructs: minimum correlation was found for psychophysical motion thresholds (DA: 0.734; LR: 0.666), while the maximum correlation was achieved with structural volume density in the neural retina (DA: 0.786; LR: 0.788). Controlling the effect of pairwise correlated visual constructs, the parameters that were most correlated to left ventricle function were volume density in retina and thickness of the retinal nerve fiber layers (adjusted multiple R2 is 0.819 and 0.730 for DA and LR), with additional contribution of psychophysical loss in achromatic contrast discrimination. We conclude that visual structural and functional changes in type 2 diabetes are related to heart dysfunction, when the effects of clinical, demographic and associated risk factors are taken into account, revealing a genuine

Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina

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Bibliowicz Jonathan

2009-10-01

Full Text Available Abstract Background The roles of the Hedgehog (Hh pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. Results To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. Conclusion Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS, a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2, and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography.

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Garcia, Jose Mauricio Botto de Barros; Isaac, David Leonardo Cruvinel; Sardeiro, Tainara; Aquino, Érika; Avila, Marcos

2017-01-01

This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980), an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Benign familial fleck retina: multimodal imaging including optical coherence tomography angiography

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Jose Mauricio Botto de Barros Garcia

Full Text Available ABSTRACT This report presents multimodal imaging of a 27-year-old woman diagnosed with benign familial fleck retina (OMIM 228980, an uncommon disorder. Fundus photographs revealed retinal flecks that affected her post-equatorial retina but spared the macular area. Fundus autofluorescence and infrared imaging demonstrated a symmetrical pattern of yellow-white fleck lesions that affected both eyes. Her full-field electroretinogram and electrooculogram were normal. An optical coherence tomography B-scan was performed for both eyes, revealing increased thickness of the retinal pigmented epithelium leading to multiple small pigmented epithelium detachments. The outer retina remained intact in both eyes. Spectral-domain optical coherence tomography angiography with split-spectrum amplitude decorrelation algorithm and 3 × 3 mm structural en face optical coherence tomography did not show macular lesions. Benign familial fleck retina belongs to a heterogenous group of so-called flecked retina syndromes, and should be considered in patients with yellowish-white retinal lesions without involvement of the macula.

Monte Carlo simulation of zinc protoporphyrin fluorescence in the retina

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Chen, Xiaoyan; Lane, Stephen

2010-02-01

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

Spontaneous high frequency diameter oscillations of larger retinal arterioles are reduced in type 2 diabetes mellitus

DEFF Research Database (Denmark)

Bek, Toke; Jeppesen, Peter; Kanters, Jørgen K.

2013-01-01

Diabetic retinopathy is characterized by morphological changes in the retina secondary to disturbances in retinal blood flow. Vasomotion is a mechanism for regulating blood flow by spontaneous oscillations in the diameter of retinal resistance arterioles, and has been shown to be disturbed outside...... the eye in diabetic patients. Therefore, the purpose of the present study was to characterize spontaneous oscillations in the diameter of retinal arterioles in normal persons and in persons with different severity of diabetic retinopathy....

Genetics of lattice degeneration of the retina.

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Murakami, F; Ohba, N

1982-01-01

First-degree relatives of proband patients with lattice degeneration of the retina revealed a significantly higher prevalence of the disease than the prevalence in the general population: the former had the disease about three times as frequently as the latter. The observed data were analyzed in terms of their accordance with recognized genetic models. The inheritance pattern did not fit well to a monogenic mode of inheritance, and it was hypothesized that a polygenic or multifactorial mode of inheritance is the most likely for lattice degeneration of the retina.

Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections.

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Levin, Ariana M; Rusu, Irene; Orlin, Anton; Gupta, Mrinali P; Coombs, Peter; D'Amico, Donald J; Kiss, Szilárd

2017-01-01

The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA.

Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections

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Levin AM

2017-01-01

Full Text Available Ariana M Levin, Irene Rusu, Anton Orlin, Mrinali P Gupta, Peter Coombs, Donald J D’Amico, Szilárd Kiss Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA Purpose: The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA following anti-vascular endothelial growth factor (VEGF intravitreal injections in patients treated for diabetic retinopathy. Methods: This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Results: Twelve of 16 eyes (75% or 11 of 15 patients (73.3% demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. Conclusion: In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA. Keywords: anti-VEGF, diabetes, diabetic retinopathy, ischemia, perfusion, reperfusion

Toward automated selective retina treatment (SRT): an optical microbubble detection technique

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Seifert, Eric; Park, Young-Gun; Theisen-Kunde, Dirk; Roh, Young-Jung; Brinkmann, Ralf

2018-02-01

Selective retina therapy (SRT) is an ophthalmological laser technique, targeting the retinal pigment epithelium (RPE) with repetitive microsecond laser pulses, while causing no thermal damage to the neural retina, the photoreceptors as well as the choroid. The RPE cells get damaged mechanically by microbubbles originating, at the intracellular melanosomes. Beneficial effects of SRT on Central Serous Retinopathy (CSR) and Diabetic Macula Edema (DME) have already been shown. Variations in the transmission of the anterior eye media and pigmentation variation of RPE yield in intra- and inter- individual thresholds of the pulse energy required for selective RPE damage. Those selective RPE lesions are not visible. Thus, dosimetry-systems, designed to detect microbubbles as an indicator for RPE cell damage, are demanded elements to facilitate SRT application. Therefore, a technique based on the evaluation of backscattered treatment light has been developed. Data of 127 spots, acquired during 10 clinical treatments of CSR patients, were assigned to a RPE cell damage class, validated by fluorescence angiography (FLA). An algorithm has been designed to match the FLA based information. A sensitivity of 0.9 with a specificity close to 1 is achieved. The data can be processed within microseconds. Thus, the process can be implemented in existing SRT lasers with an automatic pulse wise increasing energy and an automatic irradiation ceasing ability to enable automated treatment close above threshold to prevent adverse effects caused by too high pulse energy. Alternatively, a guidance procedure, informing the treating clinician about the adequacy of the actual settings, is possible.

Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

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Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

2016-01-01

There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

Damage and functional recovery of the mouse retina after exposure to genotoxic agents

International Nuclear Information System (INIS)

Vinogradova, Yu.V.; Tronov, V.A.; Lyakhova, K.N.; Ostrovskij, M.A.

2013-01-01

As is known, the mature retina is characterized by high radiation resistance. We showed earlier that ionizing radiation at a dose of ≥25 Gy and the chemical genotoxic agent methylnitrosourea (MNU) in a concentration of ≥60 mg/kg induce acute retinal degeneration, combined with proapoptotic protein expression. The process has a high genotoxic threshold, below which no degeneration signs were traced. The aim of this work was to study the damaging effect of ionizing radiation and MNU on the functional activity of the retina and its ability to recover after exposure to these genotoxicants. The functional activity of the mouse retina was evaluated with electroretinograms (ERG). In parallel, morphological changes in the retina were controlled, and the TUNEL detection of the death of its cell elements was performed. It has been shown that gamma rays or accelerated proton irradiation below 15 Gy cause no structural or functional changes in the mouse retina, which confirms the mature retina's high radiation resistance. Irradiation with a higher dose of 25 Gy leads to photoreceptor layer destruction. This goes along with an increase in the number of the TUNEL-positive photoreceptors, among which are cells with fragmented nuclei, which are typical of apoptosis. MNU in a concentration of 70 mg/kg caused the irreversible loss of the retina's physiological activity, and the morphological degeneration of photoreceptors and their mass death. In a concentration of 35 mg/kg, however, MNU had no cytotoxic effect on the retina. Moreover, this dose caused a reversible ERG amplitude decrease. Also, adaptive response was observed in the retina, which became apparent after two consecutive MNU injections - first, at a dose of 17 mg/kg; then, at a cytotoxic dose of 70 mg/kg. These results point to the possibility of the neurohormesis effect, which was described concerning the retina's exposure to ionizing radiation and some chemicals.

Localization of glycine-containing neurons in the Macaca monkey retina

International Nuclear Information System (INIS)

Hendrickson, A.E.; Koontz, M.A.; Pourcho, R.G.; Sarthy, P.V.; Goebel, D.J.

1988-01-01

Autoradiography following 3H-glycine (Gly) uptake and immunocytochemistry with a Gly-specific antiserum were used to identify neurons in Macaca monkey retina that contain a high level of this neurotransmitter. High-affinity uptake of Gly was shown to be sodium dependent whereas release of both endogenous and accumulated Gly was calcium dependent. Neurons labeling for Gly included 40-46% of the amacrine cells and nearly 40% of the bipolars. Synaptic labeling was seen throughout the inner plexiform layer (IPL) but with a preferential distribution in the inner half. Bands of labeled puncta occurred in S2, S4, and S5. Both light and postembedding electron microscopic (EM) immunocytochemistry identified different types of amacrine and bipolar cell bodies and their synaptic terminals. The most heavily labeled Gly+ cell bodies typically were amacrine cells having a single, thick, basal dendrite extending deep into the IPL and, at the EM level, electron-dense cytoplasm and prominent nuclear infoldings. This cell type may be homologous with the Gly2 cell in human retina and the AII/Gly2 of cat retina. Gly+ amacrines synapse most frequently onto Gly- amacrines and both Gly- and Gly+ bipolars. Gly+ bipolar cells appeared to be cone bipolars because their labeled dendrites could be traced only to cone pedicles. The pattern of these labeled dendritic trees indicated that both diffuse and midget types of biopolars were Gly+. The EM distribution of labeled synapses showed Gly+ amacrine synapses throughout the IPL, but these composed only 11-23% of the amacrine population. Most of the Gly+ bipolar terminals were in the inner IPL, where 70% of all bipolar terminals were labeled

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

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

2000-01-01

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

Clonal origins of cells in the pigmented retina of the zebrafish eye

International Nuclear Information System (INIS)

Streisinger, G.; Coale, F.; Taggart, C.; Walker, C.; Grunwald, D.J.

1989-01-01

Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma-irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina

General aspects of diabetes mellitus.

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Alam, Uazman; Asghar, Omar; Azmi, Shazli; Malik, Rayaz A

2014-01-01

Diabetes mellitus is a heterogeneous group of disorders characterized by hyperglycemia due to an absolute or relative deficit in insulin production or action. The chronic hyperglycemia of diabetes mellitus is associated with end organ damage, dysfunction, and failure, including the retina, kidney, nervous system, heart, and blood vessels. The International Diabetes Federation (IDF) estimated an overall prevalence of diabetes mellitus to be 366 million in 2011, and predicted a rise to 552 million by 2030. The treatment of diabetes mellitus is determined by the etiopathology and is most commonly subdivided in type 1 and type 2 diabetes mellitus. There is a greater propensity towards hyperglycemia in individuals with coexisting genetic predisposition or concomitant drug therapy such as corticosteroids. The screening for diabetes mellitus may either be in the form of a 2hour oral glucose tolerance test, or via HbA1c testing, as recently recommended by the American Diabetes Association (ADA). Strong associations have been shown in observational studies suggesting poor clinical outcomes both with chronic hyperglycemia and acutely in intensive care settings. However, tight glycemic control in this setting is a contentious issue with an increased incidence of hypoglycemia and possible increase in morbidity and mortality. In a critically ill patient a glucose range of 140-180mg/dL (7.8-10.0mmol/L) should be maintained via continuous intravenous insulin infusion.

Gastrointestinal transit in nonobese diabetic mouse: an animal model of human diabetes type 1.

Science.gov (United States)

El-Salhy, M

2001-01-01

Gastrointestinal transit (GI) in the nonobese diabetic (NOD) mouse, an animal model of human diabetes type 1, was examined in animals with short- (duration 1-5 days) and long-term (duration 28-35 days) diabetes. Blood glucose level, serum insulin concentration, and gut neuroendocrine peptide content were also measured. GI was significantly rapid in NOD mice with long-term diabetes (LTD), but was not correlated with blood glucose level, serum insulin concentration, or pancreatic insulin content. GI was correlated with duodenal secretin content, but not with the content of other neuroendocrine peptides in the different segments investigated. Whereas antral vasoactive intestinal peptide (VIP) content in NOD mice with LTD was significantly higher, colonic VIP was lower in NOD mice with short-term diabetes (STD). In the duodenum, whereas the concentration of secretin in NOD mice with both STD and LTD was lower, the gastrin content was higher. Duodenal somatostatin content in NOD mice with LTD was lower. In colon, the content of galanin in NOD mice with LTD was higher than in controls. The decreased content of secretin may be among the factors that cause rapid GI in NOD mice with LTD. Changes in the antral content of VIP, duodenal somatostatin, and colonic galanin in NOD mice with LTD may cause low intestinal secretion and, together with rapid GI, give rise to diarrhoea, which is a common symptom in diabetes.

Imaging and quantifying ganglion cells and other transparent neurons in the living human retina.

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Liu, Zhuolin; Kurokawa, Kazuhiro; Zhang, Furu; Lee, John J; Miller, Donald T

2017-11-28

Ganglion cells (GCs) are fundamental to retinal neural circuitry, processing photoreceptor signals for transmission to the brain via their axons. However, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. A major bottleneck has been our inability to observe GCs and their degeneration in the living human eye. Despite two decades of development of optical technologies to image cells in the living human retina, GCs remain elusive due to their high optical translucency. Failure of conventional imaging-using predominately singly scattered light-to reveal GCs has led to a focus on multiply-scattered, fluorescence, two-photon, and phase imaging techniques to enhance GC contrast. Here, we show that singly scattered light actually carries substantial information that reveals GC somas, axons, and other retinal neurons and permits their quantitative analysis. We perform morphometry on GC layer somas, including projection of GCs onto photoreceptors and identification of the primary GC subtypes, even beneath nerve fibers. We obtained singly scattered images by: ( i ) marrying adaptive optics to optical coherence tomography to avoid optical blurring of the eye; ( ii ) performing 3D subcellular image registration to avoid motion blur; and ( iii ) using organelle motility inside somas as an intrinsic contrast agent. Moreover, through-focus imaging offers the potential to spatially map individual GCs to underlying amacrine, bipolar, horizontal, photoreceptor, and retinal pigment epithelium cells, thus exposing the anatomical substrate for neural processing of visual information. This imaging modality is also a tool for improving clinical diagnosis and assessing treatment of retinal disease. Copyright © 2017 the Author(s). Published by PNAS.

Evidence for diffuse central retinal edema in vivo in diabetic male Sprague Dawley rats.

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Bruce A Berkowitz

Full Text Available Investigations into the mechanism of diffuse retinal edema in diabetic subjects have been limited by a lack of animal models and techniques that co-localized retinal thickness and hydration in vivo. In this study we test the hypothesis that a previously reported supernormal central retinal thickness on MRI measured in experimental diabetic retinopathy in vivo represents a persistent and diffuse edema.In diabetic and age-matched control rats, and in rats experiencing dilutional hyponatremia (as a positive edema control, whole central retinal thickness, intraretinal water content and apparent diffusion coefficients (ADC, 'water mobility' were measured in vivo using quantitative MRI methods. Glycated hemoglobin and retinal thickness ex vivo (histology were also measured in control and diabetic groups. In the dilutional hyponatremia model, central retinal thickness and water content were supernormal by quantitative MRI, and intraretinal water mobility profiles changed in a manner consistent with intracellular edema. Groups of diabetic (2, 3, 4, 6, and 9 mo of diabetes, and age-matched controls were then investigated with MRI and all diabetic rats showed supernormal whole central retinal thickness. In a separate study in 4 mo diabetic rats (and controls, MRI retinal thickness and water content metrics were significantly greater than normal, and ADC was subnormal in the outer retina; the increase in retinal thickness was not detected histologically on sections of fixed and dehydrated retinas from these rats.Diabetic male Sprague Dawley rats demonstrate a persistent and diffuse retinal edema in vivo, providing, for the first time, an important model for investigating its pathogenesis and treatment. These studies also validate MRI as a powerful approach for investigating mechanisms of diabetic retinal edema in future experimental and clinical investigations.

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina.

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Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

2015-07-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. Copyright © 2015 Elsevier Inc. All rights reserved.

[Lattice degeneration of the peripheral retina: ultrastructural study].

Science.gov (United States)

Bec, P; Malecaze, F; Arne, J L; Mathis, A

1985-01-01

The ultrastructural study of a case of snail track degeneration shows the presence of lipid inclusions in both the glial and the macrophage cells in every layer of the retina, and the existence of intraretinal fibers different from collagen fibers appearing to be glial filaments similar to those found in astrocytic gliomes and to the Rosenthal fibers observed in senile nervous cells. Other features were thinning of the retina and absence of blood vessels in the retina. There are no abnormalities of the vitreo-retinal juncture. All the lesions are in agreement with those observed by Daicker [Ophthalmologica, Basel 165: 360-365, 1972; Klin. Mbl. Augenheilk. 172: 581-583, 1978] with some differences, however. They are different from those found in lattice degeneration. They show that snail track degeneration is a specific form of peripheral retinal degeneration which is quite different from lattice degeneration and must not be considered similar.

Impact of MCT1 Haploinsufficiency on the Mouse Retina

KAUST Repository

Peachey, Neal S.

2018-05-02

The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

Impact of MCT1 Haploinsufficiency on the Mouse Retina

KAUST Repository

Peachey, Neal S.; Yu, Minzhong; Han, John Y. S.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Philp, Nancy J.

2018-01-01

The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

Impact of bronchopulmonary dysplasia on brain and retina

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Annie Wing Hoi Poon

2016-04-01

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

Investigation of the Protective Effects of Taurine against Alloxan-Induced Diabetic Retinal Changes via Electroretinogram and Retinal Histology with New Zealand White Rabbits

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Samuel Tung-Hsing Chiang

2014-01-01

Full Text Available The purpose of this study was to investigate the protective role of orally administered taurine against diabetic retinal changes via electroretinogram (ERG and retinal histology on rabbits. Rabbits were randomly assigned into groups: Group I (vehicle administration only; Group II (diabetes: induced by 100 mg/kg alloxan injection; Group III (diabetes and fed with 200 mg/kg taurine; and Group IV (diabetes and fed with 400 mg/kg taurine. The body weight and blood glucose levels of the rabbits were monitored weekly. The ERG was measured on weeks 5 and 15. Retinal histology was analyzed in the end of the experiment. Results revealed that a taurine supplement significantly ameliorates the alloxan-induced hyperglycemia and protects the retina from electrophysiological changes. Group II showed a significant (P0.05 between all groups and when compared with those of Group I. Our study provides solid evidences that taurine possesses an antidiabetic activity, reduced loss of body weight, and less electrophysiological changes of the diabetic retina.

Spontaneous activity in the developing mammalian retina: Form and function

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Butts, Daniel Allison

Spontaneous neuronal activity is present in the immature mammalian retina during the initial stages of visual system development, before the retina is responsive to light. This activity consists of bursts of action potentials fired by retinal ganglion cells, and propagates in a wavelike manner across the inner plexiform layer of the retina. Unlike waves in other neural systems, retinal waves have large variability in both their rate and direction of propagation, and individual waves only propagate across small regions of the retina. The unique properties of retinal activity arise from dynamic processes within the developing retina, and produce characteristic spatiotemporal properties. These spatiotemporal properties are of particular interest, since they are believed to play a role in visual system development. This dissertation addresses the complex spatiotemporal patterning of the retinal waves from two different perspectives. First, it proposes how the immature circuitry of the developing retina generates these patterns of activity. In order to reproduce the distinct spatiotemporal properties observed in experiments, a model of the immature retinal circuitry must meet certain requirements, which are satisfied by a coarse-grained model of the developing retina that we propose. Second, this dissertation addresses how the particular spatiotemporal patterning of the retinal waves provides information to the rest of the visual system and, as a result, can be used to guide visual system development. By measuring the properties of this information, we place constraints on the developmental mechanisms that use this activity, and show how the particular spatiotemporal properties of the retinal waves provide this information. Together, this dissertation demonstrates how the apparent complexity of retinal wave patterning can be understood both through the immature circuitry that generates it, and through the developmental mechanisms that may use it. The first three

Müller glia provide essential tensile strength to the developing retina

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MacDonald, Ryan B.; Randlett, Owen; Oswald, Julia; Yoshimatsu, Takeshi

2015-01-01

To investigate the cellular basis of tissue integrity in a vertebrate central nervous system (CNS) tissue, we eliminated Müller glial cells (MG) from the zebrafish retina. For well over a century, glial cells have been ascribed a mechanical role in the support of neural tissues, yet this idea has not been specifically tested in vivo. We report here that retinas devoid of MG rip apart, a defect known as retinoschisis. Using atomic force microscopy, we show that retinas without MG have decreased resistance to tensile stress and are softer than controls. Laser ablation of MG processes showed that these cells are under tension in the tissue. Thus, we propose that MG act like springs that hold the neural retina together, finally confirming an active mechanical role of glial cells in the CNS. PMID:26416961

Epigenetic Modifications and Diabetic Retinopathy

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Renu A. Kowluru

2013-01-01

Full Text Available Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2 and matrix metalloproteinase-9 (MMP-9 are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1, and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

Endoplasmic reticulum stress and diabetic retinopathy

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Toshiyuki Oshitari

2008-02-01

Full Text Available Toshiyuki Oshitari1,2, Natsuyo Hata1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba City, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, JapanAbstract: Endoplasmic reticulum (ER stress is involved in the pathogenesis of several diseases including Alzheimer disease and Parkinson disease. Many recent studies have shown that ER stress is related to the pathogenesis of diabetes mellitus, and with the death of pancreatic β-cells, insulin resistance, and the death of the vascular cells in the retina. Diabetic retinopathy is a major complication of diabetes and results in death of both neural and vascular cells. Because the death of the neurons directly affects visual function, the precise mechanism causing the death of neurons in early diabetic retinopathy must be determined. The ideal therapy for preventing the onset and the progression of diabetic retinopathy would be to treat the factors involved with both the vascular and neuronal abnormalities in diabetic retinopathy. In this review, we present evidence that ER stress is involved in the death of both retinal neurons and vascular cells in diabetic eyes, and thus reducing or blocking ER stress may be a potential therapy for preventing the onset and the progression of diabetic retinopathy.Keywords: endoplasmic reticulum stress, diabetic retinopathy, vascular cell death, neuronal cell death

Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients

DEFF Research Database (Denmark)

Klassen, Henry; Kiilgaard, Jens Folke; Zahir, Tasneem

2007-01-01

Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor...

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

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ROBERTO PAES-DE-CARVALHO

2002-09-01

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

Identification of endogenous flurophores in the layered retina

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Xu, Gaixia; Chen, Danni; Sun, Yiwen; Qu, Junle; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

2007-05-01

In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment epithelium cells exhibited strong autofluorescence with as emission peak of 600+/-10nm when excited with 860-nm light. The emission peak of photoreceptors was at 652+/-5nm, and the emission peak of retinal vessels layer was weak and at 640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which suggested that there wasn't only one endogenous fluorophores of tissues excited.

Increased Retinal Thinning after Combination of Internal Limiting Membrane Peeling and Silicone Oil Endotamponade in Proliferative Diabetic Retinopathy.

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Kaneko, Hiroki; Matsuura, Toshiyuki; Takayama, Kei; Ito, Yasuki; Iwase, Takeshi; Ueno, Shinji; Nonobe, Norie; Yasuda, Shunsuke; Kataoka, Keiko; Terasaki, Hiroko

2017-01-01

The aim of this study was to examine the change in retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling and/or silicone oil (SO) endotamponade in proliferative diabetic retinopathy (PDR). The actual amount and ratio of changes in the retinal thickness were calculated. Compared to control eyes in the ILM peeling (-)/SO (-) group, the central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, inferior inner, temporal inner, and nasal inner retina in the ILM peeling (+)/SO (+) group showed a significant reduction of the retinal thickness. The central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, superior inner, inferior inner, and temporal inner retina in the ILM peeling (+)/SO (+) group showed a significantly increased reduction rate of the retinal thickness compared to the control group. Macular retinal thinning in PDR was observed after ILM peeling and SO endotamponade, and it was increased by the combination of these 2 factors. © 2017 S. Karger AG, Basel.

Role of phospholipases A2 in diabetic retinopathy: in vitro and in vivo studies.

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Lupo, Gabriella; Motta, Carla; Giurdanella, Giovanni; Anfuso, Carmelina Daniela; Alberghina, Mario; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio

2013-12-01

Diabetic retinopathy is one of the leading causes of blindness and the most common complication of diabetes with no cure available. We investigated the role of phospholipases A2 (PLA2) in diabetic retinopathy using an in vitro blood-retinal barrier model (BRB) and an in vivo streptozotocin (STZ)-induced diabetic model. Mono- and co-cultures of endothelial cells (EC) and pericytes (PC), treated with high or fluctuating concentrations of glucose, to mimic the diabetic condition, were used. PLA2 activity, VEGF and PGE2 levels and cell proliferation were measured, with or without PLA2 inhibition. Diabetes was induced in rats by STZ injection and PLA2 activity along with VEGF, TNFα and ICAM-1 levels were measured in retina. High or fluctuating glucose induced BRB breakdown, and increased PLA2 activity, PGE2 and VEGF in EC/PC co-cultures; inhibition of PLA2 in mono- or co-cultures treated with high or fluctuating glucose dampened PGE2 and VEGF production down to the levels of controls. High or fluctuating glucose increased EC number and reduced PC number in co-cultures; these effects were reversed after transfecting EC with small interfering RNA targeted to PLA2. PLA2 and COX-2 protein expressions were significantly increased in microvessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNFα that were reduced by treatment with a cPLA2 inhibitor. In conclusion, the present findings indicate that PLA2 upregulation represents an early step in glucose-induced alteration of BRB, possibly upstream of VEGF; thus, PLA2 may be an interesting target in managing diabetic retinopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

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Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

2016-12-01

Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Standard anatomical and visual space for the mouse retina: computational reconstruction and transformation of flattened retinae with the Retistruct package.

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David C Sterratt

Full Text Available The concept of topographic mapping is central to the understanding of the visual system at many levels, from the developmental to the computational. It is important to be able to relate different coordinate systems, e.g. maps of the visual field and maps of the retina. Retinal maps are frequently based on flat-mount preparations. These use dissection and relaxing cuts to render the quasi-spherical retina into a 2D preparation. The variable nature of relaxing cuts and associated tears limits quantitative cross-animal comparisons. We present an algorithm, "Retistruct," that reconstructs retinal flat-mounts by mapping them into a standard, spherical retinal space. This is achieved by: stitching the marked-up cuts of the flat-mount outline; dividing the stitched outline into a mesh whose vertices then are mapped onto a curtailed sphere; and finally moving the vertices so as to minimise a physically-inspired deformation energy function. Our validation studies indicate that the algorithm can estimate the position of a point on the intact adult retina to within 8° of arc (3.6% of nasotemporal axis. The coordinates in reconstructed retinae can be transformed to visuotopic coordinates. Retistruct is used to investigate the organisation of the adult mouse visual system. We orient the retina relative to the nictitating membrane and compare this to eye muscle insertions. To align the retinotopic and visuotopic coordinate systems in the mouse, we utilised the geometry of binocular vision. In standard retinal space, the composite decussation line for the uncrossed retinal projection is located 64° away from the retinal pole. Projecting anatomically defined uncrossed retinal projections into visual space gives binocular congruence if the optical axis of the mouse eye is oriented at 64° azimuth and 22° elevation, in concordance with previous results. Moreover, using these coordinates, the dorsoventral boundary for S-opsin expressing cones closely matches

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats.

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Li, Lin; Li, Yan-Lin; Zhou, Yun-Feng; Ge, Zheng-Yan; Wang, Li-Li; Li, Zhi-Qiang; Guo, Yu-Jie; Jin, Long; Ren, Ye; Liu, Jian-Xun; Xu, Yang

2017-06-01

To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA). High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (Pdiabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment. JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.

Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

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Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

2016-04-01

Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Comparative immunolocalization of the plasma membrane calcium pump and calbindin D28K in chicken retina during embryonic development

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N. Tolosa de Talamoni

2010-05-01

Full Text Available The immunolocalization of the plasma membrane calcium pump (PMCA was studied in 4-week-old chick retina in comparison with calbindin D28K (CaBP immunostaining. We have demonstrated that the monoclonal anti-PMCA antibody 5F10 from human erythrocyte plasma membrane crossreacts with a Ca2+ pump epitope of the cells from the neural retina. The immunolocalization of both proteins was also studied during the embryonic development of the chicken retina. At age 4.5 days, the cells of the retina were faintly immunoreactive to PMCA and CaBP antibodies, but the lack of cellular aggregation and differentiation did not allow discrimination between the two proteins. A clear difference in the localization was seen from the tenth day of development through post-hatching with slight variation. PMCA localized mainly in the outer and inner plexiform layers, in some cells in the ganglion layer, in the nerve fiber layer and slightly in the photoreceptor cells. CaBP was intensely stained in cones, cone pedicles and some amacrine cells. The number of CaBP positive amacrine cells declined after hatching. A few ganglion cells and several nerve fibers were CaBP 333 immunoreactive. The role of these proteins in the early stages of retinal development is unknown, but the results suggest that Ca2+ homeostasis in the retina is well regulated, probably to avoid excessive accumulation of Ca2+, which often leads to neurodegeneration.

Comparative Aspects of Human, Canine, and Feline Obesity and Factors Predicting Progression to Diabetes

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Margarethe Hoenig

2014-01-01

Obesity and diabetes mellitus are common diseases in humans, dogs and cats and their prevalence is increasing. Obesity has been clearly identified as a risk factor for type 2 diabetes in humans and cats but recent data are missing in dogs, although there is evidence that the unprecedented rise in canine obesity in the last decade has led to a rise in canine diabetes of similar magnitude. The insulin resistance of obesity has often been portrayed as major culprit in the loss of glucose control...

Localization and Developmental Expression Patterns of CSPG in the RCS Rat Retina

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Li-Feng Chen

2011-05-01

Full Text Available Purpose: Investigate changes in chondroitin sulfate proteoglycan (CSPG distribution in Royal College of Surgeons (RCS rat retinae. Could CSPGs distribution act as a physical barrier to transplanted cell migration in degenerating retinae? Methods: CSPG expression was examined in RCS and Long-Evans rat retinae from birth to postnatal day 150 (PND150 using immunofluorescence and western-blots. Results: Both groups showed a rapid rise in CSPG expression on PND14, which peaked on PND21 before declining to lower levels by PND35. CSPG expression had risen again by PND90 and remained elevated for the duration of the study (PND150. However, from PND21, CSPG expression was significantly higher (p ≤ 0.05, n = 5 in Long-Evans rat retinae. CSPG-positive cells were localized in the ganglion cell layer (GCL and the photoreceptor outer segment debris zone (DZ; CSPG expression in the DZ was the main contributor to the higher expression in older animals for both groups. Conclusions: Increased expression of CSPGs in the DZ may act as a physical barrier following retinal cellular transplantation. CSPGs in the GCL is probably related to dendritic changes. CSPG accumulation in the older retinae suggests that aging influences the microenvironment in the retina, which may affect the efficacy of cell transplantation.

Asymmetric severity of diabetic retinopathy in Waardenburg syndrome: response to authors

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Gupta A

2012-03-01

Full Text Available Aditi Gupta, Rajiv Raman, Tarun SharmaShri Bhagwan Mahavir Department of Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, IndiaWe read with great interest the recent article by Kashima et al,1 in which the authors report a case of asymmetric severity of diabetic retinopathy in Waardenburg syndrome. We want to highlight some concerns regarding this report. Previous reports have described many systemic and local factors associated with the development of asymmetric diabetic retinopathy.2,3 These include myopia ≥5 D, anisometropia >1 D, amblyopia, unilateral elevated intraocular pressure, complete posterior vitreous detachment, unilateral carotid artery stenosis, ocular ischemic syndrome, and chorioretinal scarring.2,3 In any suspected case of asymmetric diabetic retinopathy, it is prudent to rule out the abovementioned factors first. In the present case, although the authors clearly mention the absence of internal carotid and ophthalmic artery obstruction on magnetic resonance angiography, it would have been more informative if the authors had also provided the refractive error, intraocular pressure, and posterior vitreous detachment status of both the eyes.Likewise, it would have been useful to note the arm-retina time and retinal arteriovenous filling time in both the eyes on fundus fluorescein angiography, which is usually used to diagnose ocular ischemic syndrome by monitoring extension of the retinal circulation time, including time of blood circulation from the arm to the retina and the retinal arteriovenous filling time.4,5 The mere absence of internal carotid obstruction on magnetic resonance angiography cannot rule out the presence of ocular ischemic syndrome because, rarely, ocular ischemic syndrome can also occur secondary to other causes, such as arteritis.6,7 Comparing the arm-retina time and retinal arteriovenous filling time on fundus fluorescein angiography in both the eyes would be more helpful to rule out ocular

Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity

OpenAIRE

Zhiyao Fu; Feven Berhane; Alemu Fite; Berhane Seyoum; Abdul B. Abou-Samra; Ren Zhang

2014-01-01

Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic ?-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N = 15) or diabetic (BMI- and age-matched; N = 14); b) lean or obese (N = 53 ...

Bcl-2 expression during the development and degeneration of RCS rat retinae.

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Sharma, R K

2001-12-14

In various hereditary retinal degenerations, including that in Royal College of Surgeons (RCS) rats, the photoreceptors ultimately die by apoptosis. Bcl-2 is one of the genes, which regulates apoptosis and is thought to promote survival of cells. This study has investigated the developmental expression of Bcl-2 in RCS rat, which is a well-studied animal model for hereditary retinal degeneration. An antibody against Bcl-2 was used for its immunohistochemical localization in dystrophic RCS rat retinae from postnatal (PN) days 4, 7, 13, 35, 45, 70, 202 and 14 months. Results were compared with Bcl-2 localization in congenic non-dystrophic rats from PN 4, 7, 13, 44, 202 and 14 months. Bcl-2 immunoreactivity in non-dystrophic retinae was already present in PN 4 retinae in the nerve fiber layer (presumably in the endfeet of immature Müller cells) and in the proximal parts of certain radially aligned neuroepithelial cells/immature Müller cell radial processes. With increasing age the immunoreactivity in relatively more mature Müller cell radial processes spread distally towards the outer retina and between PN 13 and 44 it reached the adult distribution. No cell bodies in the ganglion cell layer were found to be immunoreactive. Expression of Bcl-2 immunoreactivity in dystrophic RCS rat retinae closely resembled that of non-dystrophic retinae. No immunoreactivity was seen in photoreceptors or retinal pigment epithelium in dystrophic or non-dystrophic retinae. In conclusion, Bcl-2 expression is not altered, either in terms of its chronology or the cell type expressing it, during retinal degeneration in RCS rats.

Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

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

2009-01-01

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

Progranulin regulates neurogenesis in the developing vertebrate retina.

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Walsh, Caroline E; Hitchcock, Peter F

2017-09-01

We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed-retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114-1129, 2017. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.

Early diagnosis of sub-clinical stage of diabetic retinopathy

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Xing-Hui Xu

2014-12-01

Full Text Available AIM: To evaluate the early diagnosis of sub-clinic stage of diabetic retinopathy.METHODS: This was cross sectional study,multifocal retina electroretinogram(mf-ERG, contrast sensitivity(CSand central retinal artery color Doppler examination were recorded from 30 cases(30 eyesmatched control subjects, 35 cases(35 eyeswith type 2 diabetes mellitus(DMwithout diabetic retinopathy(NDRand 38 cases(38 eyeswith non-prolifera tive diabetic retinopathy(NPDR. One-way ANOVA and SNK-q test were used for data analysis.RESULTS: P1 response density of NDR patients were found decrease, N1 implicit time were delayed. Which were related with the degree of retinopathy(PPPP>0.05, The differences between normal group, NDR group and NPDR group were found statistically significant(PCONCLUSION: mf-ERG and CS are sensitive indexes for early evaluation of visual function in patients with diabetes mellitus, with development of the disease, CRA blood flow also appears to decline.

Protein changes in the retina following experimental retinal detachment in rabbits

DEFF Research Database (Denmark)

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

2011-01-01

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

Msx1 is expressed in retina endothelial cells at artery branching sites

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Miguel Lopes

2012-02-01

Msx1 and Msx2 encode homeodomain transcription factors that play a role in several embryonic developmental processes. Previously, we have shown that in the adult mouse, Msx1lacZ is expressed in vascular smooth muscle cells (VSMCs and pericytes, and that Msx2lacZ is also expressed in VSMCs as well as in a few endothelial cells (ECs. The mouse retina and choroid are two highly vascularized tissues. Vessel alterations in the retina are associated with several human diseases and the retina has been intensely used for angiogenesis studies, whereas the choroid has been much less investigated. Using the Msx1lacZ and Msx2lacZ reporter alleles, we observed that Msx2 is not expressed in the eye vascular tree in contrast to Msx1, for which we establish the spatial and temporal expression pattern in these tissues. In the retina, expression of Msx1 takes place from P3, and by P10, it becomes confined to a subpopulation of ECs at branching points of superficial arterioles. These branching sites are characterized by a subpopulation of mural cells that also show specific expression programs. Specific Msx gene inactivation in the endothelium, using Msx1 and Msx2 conditional mutant alleles together with a Tie2-Cre transgene, did not lead to conspicuous structural defects in the retinal vascular network. Expression of Msx1 at branching sites might therefore be linked to vessel physiology. The retinal blood flow is autonomously regulated and perfusion of capillaries has been proposed to depend on arteriolar precapillary structures that might be the sites for Msx1 expression. On the other hand, branching sites are subject to shear stress that might induce Msx1 expression. In the choroid vascular layer Msx1lacZ is expressed more broadly and dynamically. At birth Msx1lacZ expression takes place in the endothelium but at P21 its expression has shifted towards the mural layer. We discuss the possible functions of Msx1 in the eye vasculature.

Msx1 is expressed in retina endothelial cells at artery branching sites.

Science.gov (United States)

Lopes, Miguel; Goupille, Olivier; Saint Cloment, Cécile; Robert, Benoît

2012-04-15

Msx1 and Msx2 encode homeodomain transcription factors that play a role in several embryonic developmental processes. Previously, we have shown that in the adult mouse, Msx1(lacZ) is expressed in vascular smooth muscle cells (VSMCs) and pericytes, and that Msx2(lacZ) is also expressed in VSMCs as well as in a few endothelial cells (ECs). The mouse retina and choroid are two highly vascularized tissues. Vessel alterations in the retina are associated with several human diseases and the retina has been intensely used for angiogenesis studies, whereas the choroid has been much less investigated. Using the Msx1(lacZ) and Msx2(lacZ) reporter alleles, we observed that Msx2 is not expressed in the eye vascular tree in contrast to Msx1, for which we establish the spatial and temporal expression pattern in these tissues. In the retina, expression of Msx1 takes place from P3, and by P10, it becomes confined to a subpopulation of ECs at branching points of superficial arterioles. These branching sites are characterized by a subpopulation of mural cells that also show specific expression programs. Specific Msx gene inactivation in the endothelium, using Msx1 and Msx2 conditional mutant alleles together with a Tie2-Cre transgene, did not lead to conspicuous structural defects in the retinal vascular network. Expression of Msx1 at branching sites might therefore be linked to vessel physiology. The retinal blood flow is autonomously regulated and perfusion of capillaries has been proposed to depend on arteriolar precapillary structures that might be the sites for Msx1 expression. On the other hand, branching sites are subject to shear stress that might induce Msx1 expression. In the choroid vascular layer Msx1(lacZ) is expressed more broadly and dynamically. At birth Msx1(lacZ) expression takes place in the endothelium but at P21 its expression has shifted towards the mural layer. We discuss the possible functions of Msx1 in the eye vasculature.

Application of Novel Software Algorithms to Spectral-Domain Optical Coherence Tomography for Automated Detection of Diabetic Retinopathy.

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Adhi, Mehreen; Semy, Salim K; Stein, David W; Potter, Daniel M; Kuklinski, Walter S; Sleeper, Harry A; Duker, Jay S; Waheed, Nadia K

2016-05-01

To present novel software algorithms applied to spectral-domain optical coherence tomography (SD-OCT) for automated detection of diabetic retinopathy (DR). Thirty-one diabetic patients (44 eyes) and 18 healthy, nondiabetic controls (20 eyes) who underwent volumetric SD-OCT imaging and fundus photography were retrospectively identified. A retina specialist independently graded DR stage. Trained automated software generated a retinal thickness score signifying macular edema and a cluster score signifying microaneurysms and/or hard exudates for each volumetric SD-OCT. Of 44 diabetic eyes, 38 had DR and six eyes did not have DR. Leave-one-out cross-validation using a linear discriminant at missed detection/false alarm ratio of 3.00 computed software sensitivity and specificity of 92% and 69%, respectively, for DR detection when compared to clinical assessment. Novel software algorithms applied to commercially available SD-OCT can successfully detect DR and may have potential as a viable screening tool for DR in future. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:410-417.]. Copyright 2016, SLACK Incorporated.

Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

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de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

2010-04-01

The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the

Development of a screening tool for staging of diabetic retinopathy in fundus images

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Dhara, Ashis Kumar; Mukhopadhyay, Sudipta; Bency, Mayur Joseph; Rangayyan, Rangaraj M.; Bansal, Reema; Gupta, Amod

2015-03-01

Diabetic retinopathy is a condition of the eye of diabetic patients where the retina is damaged because of long-term diabetes. The condition deteriorates towards irreversible blindness in extreme cases of diabetic retinopathy. Hence, early detection of diabetic retinopathy is important to prevent blindness. Regular screening of fundus images of diabetic patients could be helpful in preventing blindness caused by diabetic retinopathy. In this paper, we propose techniques for staging of diabetic retinopathy in fundus images using several shape and texture features computed from detected microaneurysms, exudates, and hemorrhages. The classification accuracy is reported in terms of the area (Az) under the receiver operating characteristic curve using 200 fundus images from the MESSIDOR database. The value of Az for classifying normal images versus mild, moderate, and severe nonproliferative diabetic retinopathy (NPDR) is 0:9106. The value of Az for classification of mild NPDR versus moderate and severe NPDR is 0:8372. The Az value for classification of moderate NPDR and severe NPDR is 0:9750.

Measuring mouse retina response near the detection threshold to direct stimulation of photons with sub-poisson statistics

Science.gov (United States)

Tavala, Amir; Dovzhik, Krishna; Schicker, Klaus; Koschak, Alexandra; Zeilinger, Anton

Probing the visual system of human and animals at very low photon rate regime has recently attracted the quantum optics community. In an experiment on the isolated photoreceptor cells of Xenopus, the cell output signal was measured while stimulating it by pulses with sub-poisson distributed photons. The results showed single photon detection efficiency of 29 +/-4.7% [1]. Another behavioral experiment on human suggests a less detection capability at perception level with the chance of 0.516 +/-0.01 (i.e. slightly better than random guess) [2]. Although the species are different, both biological models and experimental observations with classical light stimuli expect that a fraction of single photon responses is filtered somewhere within the retina network and/or during the neural processes in the brain. In this ongoing experiment, we look for a quantitative answer to this question by measuring the output signals of the last neural layer of WT mouse retina using microelectrode arrays. We use a heralded downconversion single-photon source. We stimulate the retina directly since the eye lens (responsible for 20-50% of optical loss and scattering [2]) is being removed. Here, we demonstrate our first results that confirms the response to the sub-poisson distributied pulses. This project was supported by Austrian Academy of Sciences, SFB FoQuS F 4007-N23 funded by FWF and ERC QIT4QAD 227844 funded by EU Commission.

Pannexin1 in the outer retina of the zebrafish, Danio rerio

NARCIS (Netherlands)

Prochnow, N.; Hoffmann, S.; Vroman, R.; Klooster, J.; Bunse, S.; Kamermans, M.; Dermietzel, R.; Zoidl, G.

2009-01-01

In the retina, chemical and electrical synapses couple neurons into functional networks. New candidates encoding for electrical synapse proteins have recently emerged. In the present study, we determined the localization of the candidate protein pannexin1 (zfPanx1) in the zebrafish retina and

Role of endothelial dysfunction in the pathogenesis of diabetic retinopathy in patients with type 2 diabetes

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I. V. Vorobyeva

2014-07-01

Full Text Available The reason for the progressive vision reduction at diabetes mellitus (DM is diabetic retinopathy (DR. When type 2 diabetes combined with hypertension (Ht, it increases the risk of vision loss by 25 times. In the pathogenesis of DR is important to endothelial dysfunction and a variety of biochemical processes (an excess of intracellular sorbitol, non-enzymatic glycation of proteins, oxidative stress. there is a decrease in generation vasodilating factors, nitric oxide, with a simultaneous increase of endothelin, which causes vasoconstriction. Key processes underlying the development of DR, such as increased vascular permeability, edema, neovasculariza- tion, inflammation and associated with the effects of kallikrein-kinin system. In the pathogenesis of DR can be involved independent intraocular renin-angiotensin system, which is an important mediator of angiogenesis and increased vascular permeability. Damage to the endothelium of retinal vessels leads to ischemia of the retina. there is growth and development of newly formed blood vessels, which may provoke recurrent bleeding.

Optic nerve signals in a neuromorphic chip I: Outer and inner retina models.

Science.gov (United States)

Zaghloul, Kareem A; Boahen, Kwabena

2004-04-01

We present a novel model for the mammalian retina and analyze its behavior. Our outer retina model performs bandpass spatiotemporal filtering. It is comprised of two reciprocally connected resistive grids that model the cone and horizontal cell syncytia. We show analytically that its sensitivity is proportional to the space-constant-ratio of the two grids while its half-max response is set by the local average intensity. Thus, this outer retina model realizes luminance adaptation. Our inner retina model performs high-pass temporal filtering. It features slow negative feedback whose strength is modulated by a locally computed measure of temporal contrast, modeling two kinds of amacrine cells, one narrow-field, the other wide-field. We show analytically that, when the input is spectrally pure, the corner-frequency tracks the input frequency. But when the input is broadband, the corner frequency is proportional to contrast. Thus, this inner retina model realizes temporal frequency adaptation as well as contrast gain control. We present CMOS circuit designs for our retina model in this paper as well. Experimental measurements from the fabricated chip, and validation of our analytical results, are presented in the companion paper [Zaghloul and Boahen (2004)].

Thyroid Hormone Signaling in the Mouse Retina.

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Patrick Arbogast

Full Text Available Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3 and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells showed strong β-gal labeling. In the inner nuclear layer (INL, a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic 'starburst' amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.

Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways

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Wayne Young Liu

2016-12-01

Full Text Available Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg or fenofibric acid (100 mg/kg was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects.

Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans

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Leonore Wigger

2017-02-01

Full Text Available Summary: Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D. Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D. : Wigger et al. find that several sphingolipids in mouse plasma correlate with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in human plasma from two cohorts reveal that dihydroceramides are significantly elevated in individuals progressing to diabetes, up to 9 years before disease onset. Keywords: diabetes, T2D, ceramides, dihydroceramides, biomarkers, lipidomics, prognostic, mouse, human, high-fat diet, metabolic challenge, glucose intolerance, insulin sensitivity, prospective cohort

Modeling and Simulation of Microelectrode-Retina Interactions

Energy Technology Data Exchange (ETDEWEB)

Beckerman, M

2002-11-30

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

Direct transdifferentiation in the vertebrate retina.

Science.gov (United States)

Opas, M; Dziak, E

1998-03-01

Transdifferentiation is the process by which differentiated cells alter their identity to become other, distinct cell types. The conversion of neural retina into lens epithelium is one of the most spectacular examples of transdifferentiation. We show that the redirection of cell fate from neural retina to lens and subsequent transdifferentiation is independent of cell replication as it occurs in growth-arrested cell populations. Using DNA ratiometry of individual cells in these cultures we show that, indeed, individual amitotic cells do transdifferentiate. Hence, choice of fate in transdifferentiating cells does not rely on a "community effect" but instead can be categorized as a leadership effect> For lack of overt lens progenitors, and most importantly, for its mitotic independence, we conclude that lens colony formation in vitro does occur by direct transdifferentiation and not by clonal proliferation of progenitor cells.

[Deficient prevention and late treatment of diabetic retinopathy in Mexico].

Science.gov (United States)

Cervantes-Castañeda, René A; Menchaca-Díaz, Rufino; Alfaro-Trujillo, Beatriz; Guerrero-Gutiérrez, Manuel; Chayet-Berdowsky, Arturo S

2014-01-01

Retinopathy is a frequent complication of diabetes, causing visual impairment in 10% and blindness in 2% of diabetic patients. The aim of this study is to describe the clinical profile of diabetic patients in an ophthalmologic unit in Tijuana, México. Retrospective study of a random sample of 500 clinical charts of patients with diabetes who attended the Retina Service of "Fundación CODET para la Prevención de la Ceguera IBP" Ophthalmologic Center between 2006 and 2010. The main complaint of 58% of patients was decreased visual acuity in first evaluation. Only 6.2% of patients were referred by a health professional. Forty-six percent of the patients had a history of diabetes of at least 15 years. Thirty percent had clinically significant visual impairment at first visit, which was associated with a long history of diabetes and previous eye surgery. Twenty-five percent of these patients who were treated at our clinic experienced visual deterioration due to advanced retinopathy. Patients with diabetic retinopathy are referred to ophthalmological service tardily, when visual loss is usually severe and irreversible.

Distribution of photon absorption rates across the rat retina.

Science.gov (United States)

Williams, T P; Webbers, J P; Giordano, L; Henderson, R P

1998-04-15

1. An investigation into the distribution of light intensity across the rat retina was carried out on excised, intact rat eyes exposed to Ganzfeld illumination from a helium-neon laser (543 nm). 2. Some of the light entering the eyes exits through the sclera where its intensity can be monitored with an optical 'pick-up' that samples the intensity coming from a small region of external sclera and underlying retina. The spatial resolution of the pick-up is such that it samples light that has passed through ca 2 % of the rods in the rat eye. 3. Some of the laser light is absorbed by the rod pigment, rhodopsin, which gradually bleaches. Bleaching in the retina, in turn, causes an exponential increase in intensity emanating from the sclera. By monitoring this intensity increase, we are able to measure two important parameters in a single bleaching run: the local rhodopsin concentration and the local intensity falling on the rods. 4. With an ocular transmission photometer, we have measured both the local intensity and the local rhodopsin concentration across wide regions of rat retina. Both pigmented and albino rats were studied. 5. The distributions of rhodopsin and intensity were both nearly uniform; consequently, the product, (rhodopsin concentration) x (intensity), was similarly nearly equal across the retina. This means that the initial rate of photon absorption is about the same at all retinal locations. 6. Interpreted in terms of photostasis (the regulation of daily photon catch), this means that the rate of photon absorption is about the same in each rod, viz. 14 400 photons absorbed per rod per second. Since this rate of absorption is sufficient to saturate the rod, one possible purpose of photostasis is to maintain the rod system in a saturated state during daylight hours.

Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice

Energy Technology Data Exchange (ETDEWEB)

Geiger, Adolf, E-mail: ageiger@dreirosen-pharma.com; Walker, Audrey, E-mail: awalker@dreirosen-pharma.com; Nissen, Erwin, E-mail: enissen@dreirosen-pharma.com

2015-11-13

Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. - Highlights: • Fibrocytes have shown potent wound healing properties in vitro and in vivo. • Their clinical use is precluded by low numbers and antigen-presenting function. • We isolated exosomes with no immunogenicity potential from human fibrocytes. • Their cargo included microRNAs and proteins that are known healing promoters. • They accelerated wound closure in diabetic mice in a dose-dependent manner.

Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors

International Nuclear Information System (INIS)

Tilton, R.G.; Chang, K.; Pugliese, G.; Eades, D.M.; Province, M.A.; Sherman, W.R.; Kilo, C.; Williamson, J.R.

1989-01-01

This study investigated hemodynamic changes in diabetic rats and their relationship to changes in vascular albumin permeation and increased metabolism of glucose to sorbitol. The effects of 6 wk of streptozocin-induced diabetes and three structurally different inhibitors of aldose reductase were examined on (1) regional blood flow (assessed with 15-microns 85Sr-labeled microspheres) and vascular permeation by 125I-labeled bovine serum albumin (BSA) and (2) glomerular filtration rate (assessed by plasma clearance of 57Co-labeled EDTA) and urinary albumin excretion (determined by radial immunodiffusion assay). In diabetic rats, blood flow was significantly increased in ocular tissues (anterior uvea, posterior uvea, retina, and optic nerve), sciatic nerve, kidney, new granulation tissue, cecum, and brain. 125I-BSA permeation was increased in all of these tissues except brain. Glomerular filtration rate and 24-h urinary albumin excretion were increased 2- and 29-fold, respectively, in diabetic rats. All three aldose reductase inhibitors completely prevented or markedly reduced these hemodynamic and vascular filtration changes and increases in tissue sorbitol levels in the anterior uvea, posterior uvea, retina, sciatic nerve, and granulation tissue. These observations indicate that early diabetes-induced hemodynamic changes and increased vascular albumin permeation and urinary albumin excretion are aldose reductase-linked phenomena. Discordant effects of aldose reductase inhibitors on blood flow and vascular albumin permeation in some tissues suggest that increased vascular albumin permeation is not entirely attributable to hemodynamic change

Clinical application of OCTA in observation of macular blood flow density in patients with diabetic retinopathy

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Xiang Xiang

2017-07-01

Full Text Available AIM: Using optical coherence tomography angiography(OCTAto observe the changes and clinical significance of macular blood flow density in patients with diabetic retinopathy(DR.METHODS: Totally 47 eyes(28 patientswith diabetic retinopathy(DRwere enrolled in the DR group. According to the international clinical grading criteria of diabetic retinopathy, 30 eyes(19 patientswith non-proliferative diabetic retinopathy were classified as the NPDR group, and 17 eyes(11 patientswith proliferative diabetic retinopathy were classified as PDR group. A total of 46(27 subjectshealthy eyes with matched age were enrolled in the control group. All the subjects underwent the 3mm×3mm scanning of macular retina by optical coherence tomography angiography(OCTA, obtaining 4 levels of macular blood flow density map. The macular blood flow density at 3 levels, including superficial retinal layer, deep retinal layer and choroidal capillaries layer, were measured. RESULTS: The macular blood flow density of superfical retinal layer, deep retinal layer and choroidal capillaries layer in DR group were 0.4963±0.0840, 0.4798±0.0801 and 0.5290±0.0528, respectively. Among them, the blood flow density of each layer were 0.5064±0.0843,0.4983±0.0766,0.5345±0.0529, respectively, for the NPDR group, and were 0.4786±0.0830, 0.4473±0.0778,0.5192±0.0526, respectively, for the PDR group. For the control group, the density of each layers were 0.5919±0.0704, 0.6301±0.0527, 0.5691±0.0169, respectively. The macular blood flow density was significantly different in the superficial retinal layer, deep retinal layer and choroidal capillary layer between the control group and the NPDR group, as well as the PDR group and the DR group(total PP=0.029, but not in the superficial retina layer and choroid capillary layer(P=0.236, 0.268. CONCLUSION: Compared with the control group, the macular blood flow density of superficial retinal layer, deep retinal layer and choroidal capillary

Association between the number of natural teeth and diabetic retinopathy among type 2 diabetes mellitus: The Korea national health and nutrition examination survey.

Science.gov (United States)

Song, Su Jeong; Han, Kyungdo; Lee, Seong-Su; Park, Jun-Beom

2017-11-01

The aim of this study was to investigate the relationship between the number of teeth and diabetic retinopathy among Korean population.This was a retrospective analysis using data of total 45,811 individuals who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) 2008 to 2012. Among these, 2593 (5.7%) participants were identified as having type 2 diabetes mellitus. After excluding participants without ophthalmic evaluation or other variables, 2078 (80%) participants were included. Demographic factors including dental status were analyzed and compared between participants with and without diabetic retinopathy.Among the 2078 type 2 diabetes, 358 (17.2%) had diabetic retinopathy. Type 2 diabetes with fewer teeth were more likely to have diabetic retinopathy (P diabetes with diabetic retinopathy when compared with type 2 diabetes with ≥28 teeth (95% confidence interval: 2.69-28.3) after adjusting for age, sex, body mass index, smoking, drinking, exercise, hypertension, diabetes mellitus duration, and glycated hemoglobin level.The number of teeth was found to be an independent risk factor for diabetic retinopathy. Thus, a comprehensive approach of dentists and ophthalmologists is needed to minimize the complications of diabetes mellitus. Whether the teeth number reflects microvascular changes of the retina among type 2 diabetes warrants further investigation. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

A review on exudates detection methods for diabetic retinopathy.

Science.gov (United States)

Joshi, Shilpa; Karule, P T

2018-01-01

The presence of exudates on the retina is the most characteristic symptom of diabetic retinopathy. As exudates are among early clinical signs of DR, their detection would be an essential asset to the mass screening task and serve as an important step towards automatic grading and monitoring of the disease. Reliable identification and classification of exudates are of inherent interest in an automated diabetic retinopathy screening system. Here we review the numerous early studies that used for automatic exudates detection with the aim of providing decision support in addition to reducing the workload of an ophthalmologist. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Melatonin and diabetes: from pathophysiology to the treatment perspectives

Directory of Open Access Journals (Sweden)

Vladimir Iosifovich Konenkov

2013-06-01

Full Text Available Pineal hormone melatonin synchronizes insulin secretion and glucose homeostasis with solar periods. Misalliance between melatonin-mediated circadian rhythms and insulin secretion characterizes diabetes mellitus type 1 (T1DM and type 2 (T2DM. Insulin deficiency in T1DM is accompanied by increased melatonin production. Conversely, T2DM is characterized by diminished melatonin secretion. In genome-wide association studies the variants of melatonin receptor MT2 gene (rs1387153 and rs10830963 were associated with fasting glucose, beta-cell function and T2DM. In experimental models of diabetes melatonin enhanced beta-cell proliferation and neogenesis, improved insulin resistance and alleviated oxidative stress in retina and kidneys. However, further investigation is required to assess the therapeutic value of melatonin in diabetic patients.

Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Liping Yang; Lemeng Wu; Dongmei Wang; Ying Li; Hongliang Dou; Mark OMTso; Zhizhong Ma

2013-01-01

Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly in-creased, which was associated with retinal ganglion celldeath in diabetic retinas. The C/ERB ho-mologous protein pathway directly contributed to glial reactivity, and was subsequently responsible for neuronal loss and vascular abnormalities in diabetic retinopathy. Our experimental findings in-dicate that endoplasmic reticulum stress plays an important role in diabetes-induced retinal neu-ronal loss and vascular abnormalities, and that inhibiting the activation of the endoplasmic reticulum stress pathway provides effective protection against diabetic retinopathy.

Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys.

Science.gov (United States)

Johnson, Elizabeth J; Neuringer, Martha; Russell, Robert M; Schalch, Wolfgang; Snodderly, D Max

2005-02-01

Macular pigment (MP) is composed of the xanthophylls lutein (L) and zeaxanthin (Z) and may help to prevent age-related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls. From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 micromol/kg per day for 24 to 101 weeks. At baseline and at 4- to 12-week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina (central 4 mm, 8-mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet. Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R,3'S-Z (RSZ or meso-Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula (central 4 mm). All-trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z. L is the precursor of RSZ, a major component of macular pigment. Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion.

Changes in acetylcholine release from the chick retina are not associated with myopia development

International Nuclear Information System (INIS)

Vessey, K.A.; Cotriall, C.L.; McBrien, N.A.

2002-01-01

Full text: The effectiveness of muscarinic receptor antagonists in inhibiting myopia progression in animal models and humans implicates cholinergic signalling in ocular growth regulation. Therefore to determine if changes in the release of acetylcholine from the retina are involved in myopia development, the efflux of acetylcholine from the in vitro retina of normal and myopic chick eyes was investigated. Chicks were monocularly deprived (MD) of pattern vision with translucent occluders for 2 or 7 days and refractive error of MD groups and age matched normals was monitored using retinoscopy (n=6 each group). 3 H-choline-Cl (1 Ci in 7μL) was injected into the vitreous of each eye under 2.5% halothane anaesthesia. After 1hr, the eyes were enucleated, under terminal anaesthesia (sodium pentobarbital, 120 mg/kg, im). Retinas were flat-mounted on acetate filter discs and superfused with oxygenated physiological saline solution (PSS) for 30min at 0.4mL/min. Five baseline fractions were collected (B1-B5), then three stimulated fractions were collected in the presence of PSS containing 50mM KCl (K1-K3) at 2min intervals. 3 H-acetylcholine ( 3 H-ACh) in each fraction was quantified by liquid scintillation counting. Significant amounts of myopia were induced in MD eyes after 2 (-5.1±0.8D) and 7 days (-18.8±2.4D) relative to control eyes (paired t-test p 3 H-ACh release was 146±15% above basal levels (K2/B1%) from retinas of normal animals. After 2 days MD, there was no significant difference between KCl-evoked release of 3 H-ACh from deprived eyes (147 39%) compared to control eyes (198±61%, paired t-test, p=0.27) or the eyes of normal animals (ANOVA, p>0.5). Similar results were obtained following 7 days MD. The results demonstrate that evoked acetylcholine release from the chick retina of myopic eyes is unaltered relative to control or normal eyes using an in vitro approach. Copyright (2002) Australian Neuroscience Society

Frequency of Toxoplasma gondii in the retina in eye banks in Brazil.

Science.gov (United States)

Costa, Deise F; Nascimento, Heloisa; Sutili, Aline; Nobrega, Fernando A J; Fowler, Flavio; Nobrega, Mario Junqueira; Garrido, Cristina; de Oliveira Dias, Janaina; Adán, Consuelo B D; Rizzo, Luiz Vicente; Silveira, Claudio; Belfort, Rubens; Commodaro, Alessandra G

2017-07-01

Ocular toxoplasmosis is the main cause of posterior uveitis worldwide frequently leading to vision loss. In Brazil, the seroprevalence of Toxoplasma gondii infection ranges from 50 to 80% depending of the region studied. The frequency of toxoplasmic retinal scar may reach 18% of the adults in the South of Brazil. Our goal was to determine the frequency of T. gondii DNA in retinas from eye banks from different regions in Brazil. A total of 162 eyes were obtained from eye banks in Manaus (n = 60), Sao Paulo (n = 60), Chapeco (n = 26), and Joinville (n = 16). The retinas were macroscopically analyzed and collected for DNA extraction. Real-time PCR (qPCR) was performed using the T. gondii B1 marker. By qPCR, a higher frequency of T. gondii DNA in the retinas from the eye bank of Joinville (25%) was found when compared to Manaus (5%). The retinas from Sao Paulo and Chapeco were qPCR negative. Clinical examination determined the retina lesions to be compatible with toxoplasmosis in the following frequencies: Joinville (62.5%), Manaus (10%), Sao Paulo (6.7%), and Chapeco (15.4%).

Some indications of structural damage in retina by heavy ion radiation

International Nuclear Information System (INIS)

Nelson, A.C.; Hayes, T.L.; Tobias, C.A.; Yang, T.C.

1981-01-01

At the Lawrence Berkeley Laboratory Bevalac Facility, iron nuclei were accelerated to an energy of 600 MeV/amu. The beam of iron thus obtained was used to irradiate living biological specimens in order to study possible microscopic tissue damage with the aid of SEM. The experiments involved total head irradiation of live rats which were subsequently returned to their cages to remain for 1 day and 30 days before further examination. After the 1 day and 30 day waits, both eyes were enucleated and placed in chemical fixative followed by ethanol dehydration and critical point drying. Retinas were carefully removed from the eye cups and loaded separately on aluminum stubs which were sputter coated. SEM of the 1 day and 30 day retinas revealed lesions which were not found at all in control retinas. The 1 day and 30 day retinas manifest regions where outer rod segments were missing or rearranged. A single energetic iron nucleus may be capable of generating a retinal lesion which becomes enlarged as biological processes intervene during the 1 day and 30 day waits. Being composed of highly specialized nerve cells, retinas cannot regenerate following irradiation which severely damages the rod cells. Thus one would expect the observed radiation induced retinal lesions to correspond to permanent tissue damage and possible loss of visual acuity in the intact animal

A model of the human retina

DEFF Research Database (Denmark)

Jørgensen, John Leif

1998-01-01

Traditionally, the human eye is perceived as being "just" a camera, that renders an accurate, although limited, image for processing in the brain. This interpretation probably stems from the apparent similarity between a video- or photo-camera and a human eye with respect to the lens, the iris...

Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome

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Kimball Scot R

2011-05-01

Full Text Available Abstract Background Diabetic retinopathy (DR is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia. Methods The retina transcriptome (22,523 genes and transcript variants was examined after three months of streptozotocin-induced diabetes in male Sprague Dawley rats with and without insulin replacement for the later one and a half months of diabetes. Selected gene expression changes were confirmed by qPCR, and also examined in independent control and diabetic rats at a one month time-point. Results Transcriptomic alterations in response to diabetes (1376 probes were clustered according to insulin responsiveness. More than half (57% of diabetes-induced mRNA changes (789 probes observed at three months were fully normalized to control levels with insulin therapy, while 37% of probes (514 were only partially normalized. A small set of genes (5%, 65 probes was significantly dysregulated in the insulin-treated diabetic rats. qPCR confirmation of findings and examination of a one month time point allowed genes to be further categorized as prevented or rescued with insulin therapy. A subset of genes (Ccr5, Jak3, Litaf was confirmed at the level of protein expression, with protein levels recapitulating changes in mRNA expression. Conclusions These results provide the first genome-wide examination of the effects of insulin therapy on retinal gene expression changes with diabetes. While insulin clearly normalizes the majority of genes dysregulated in response to diabetes, a number of genes related to inflammatory processes, microvascular integrity, and neuronal function are still altered in expression in

Rod photoreceptors express GPR55 in the adult vervet monkey retina

DEFF Research Database (Denmark)

Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

2013-01-01

. Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells) and CB2R in glial...

Functional and Cellular Responses to Laser Injury in the Rat Snake Retina

National Research Council Canada - National Science Library

Glickman, Randolph D; Elliott, III, W. R; Kumar, Neeru

2007-01-01

.... This animal is of interest for vision research because its eye has an all-cone retina. A linear array of 5 thermal lesions was placed in the retina of anesthetized animals, near the area centralis, using a Nd:VO4 laser (532 nm...

Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy

DEFF Research Database (Denmark)

Scott, Ingrid U; Jackson, Gregory R; Quillen, David A

2014-01-01

IMPORTANCE: Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR). OBJECTIVES: To investigate, in a proof-of-concept clinical trial, whether low-dose oral doxycycline monohydrate can (1) slow the deterioration of, or improve, retinal function or (2) induce regression or slow......: We conducted a randomized, double-masked, 24-month proof-of-concept clinical trial. Thirty patients (from hospital-based retina practices) with 1 or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study-defined high-risk PDR. INTERVENTIONS: Patients were randomized...... adaptation, visual acuity, and quality of life) and anatomic factors (Early Treatment Diabetic Retinopathy Study DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters). RESULTS: From baseline to month 24, mean FDP foveal sensitivity decreased...

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

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Tao, Ye [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China); Chen, Tao [Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi' an 710032 (China); Liu, Bei [Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi' an (China); Yang, Guo Qing [Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi' an 710032 (China); Peng, Guanghua [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China); Zhang, Hua [Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi' an (China); Huang, Yi Fei [Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853 (China)

2015-07-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration. �

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

International Nuclear Information System (INIS)

Tao, Ye; Chen, Tao; Liu, Bei; Yang, Guo Qing; Peng, Guanghua; Zhang, Hua; Huang, Yi Fei

2015-01-01

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration. �

The Neural Retina in Retinopathy of Prematurity

Science.gov (United States)

Hansen, Ronald M.; Moskowitz, Anne; Akula, James D.; Fulton, Anne B.

2016-01-01

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease. We used noninvasive electroretinographic (ERG), psychophysical, and retinal imaging procedures to study the function and structure of the neurosensory retina. Rod photoreceptor and post-receptor responses are significantly altered years after the preterm days during which ROP is an active disease. The alterations include persistent rod dysfunction, and evidence of compensatory remodeling of the post-receptor retina is found in ERG responses to full-field stimuli and in psychophysical thresholds that probe small retinal regions. In the central retina, both Mild and Severe ROP delay maturation of parafoveal scotopic thresholds and are associated with attenuation of cone mediated multifocal ERG responses, significant thickening of post-receptor retinal laminae, and dysmorphic cone photoreceptors. These results have implications for vision and control of eye growth and refractive development and suggest future research directions. These results also lead to a proposal for noninvasive management using light that may add to the currently invasive therapeutic armamentarium against ROP. PMID:27671171

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

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Jack W Hickmott

2016-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

Retina-like sensor image coordinates transformation and display

Science.gov (United States)

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

2015-03-01

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

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

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Ignacio M Larrayoz

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

Autofluorescence from the outer retina and subretinal space: hypothesis and review.

Science.gov (United States)

Spaide, Richard

2008-01-01

To review the pathophysiologic principles underlying increased autofluorescence from the outer retina and subretinal space using selected diseases as examples. The ocular imaging information and histopathologic features, when known, were integrated for diseases causing increased autofluorescence from the outer retina and subretinal space. Inferences were taken from this information and used to create a classification scheme. These diseases are principally those that cause separation of the outer retina from the retinal pigment epithelium, thereby preventing proper phagocytosis of photoreceptor outer segments. The separation can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space. Lack of normal outer segment processing initially leads to increased accumulation of outer segments on the outer retina and subretinal space. Over time, this material is visible as an increasingly thick coating on the outer retina, is yellow, and is autofluorescent. Over time, atrophy develops with thinning of the deposited material and decreasing autofluorescence. The accumulated material is ultimately capable of inducing damage to the retinal pigment epithelium. Diseases causing accumulation of the material include central serous chorioretinopathy, vitelliform macular dystrophy, acute exudative polymorphous vitelliform maculopathy, choroidal tumors, and vitreomacular traction syndrome. The physical separation of the retinal outer segments from the retinal pigment epithelium hinders proper phagocytosis of the outer segments. Accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina.

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Astrid Zayas-Santiago

Full Text Available Müller cells, the principal glial cells of the vertebrate retina, are fundamental for the maintenance and function of neuronal cells. In most vertebrates, including humans, Müller cells abundantly express Kir4.1 inwardly rectifying potassium channels responsible for hyperpolarized membrane potential and for various vital functions such as potassium buffering and glutamate clearance; inter-species differences in Kir4.1 expression were, however, observed. Localization and function of potassium channels in Müller cells from the retina of crocodiles remain, hitherto, unknown.We studied retinae of the Spectacled caiman (Caiman crocodilus fuscus, endowed with both diurnal and nocturnal vision, by (i immunohistochemistry, (ii whole-cell voltage-clamp, and (iii fluorescent dye tracing to investigate K+ channel distribution and glia-to-neuron communications.Immunohistochemistry revealed that caiman Müller cells, similarly to other vertebrates, express vimentin, GFAP, S100β, and glutamine synthetase. In contrast, Kir4.1 channel protein was not found in Müller cells but was localized in photoreceptor cells. Instead, 2P-domain TASK-1 channels were expressed in Müller cells. Electrophysiological properties of enzymatically dissociated Müller cells without photoreceptors and isolated Müller cells with adhering photoreceptors were significantly different. This suggests ion coupling between Müller cells and photoreceptors in the caiman retina. Sulforhodamine-B injected into cones permeated to adhering Müller cells thus revealing a uni-directional dye coupling.Our data indicate that caiman Müller glial cells are unique among vertebrates studied so far by predominantly expressing TASK-1 rather than Kir4.1 K+ channels and by bi-directional ion and uni-directional dye coupling to photoreceptor cells. This coupling may play an important role in specific glia-neuron signaling pathways and in a new type of K+ buffering.

Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration

Science.gov (United States)

Haynes, Tracy; Luz-Madrigal, Agustin; Reis, Edimara S.; Echeverri Ruiz, Nancy P.; Grajales-Esquivel, Erika; Tzekou, Apostolia; Tsonis, Panagiotis A.; Lambris, John D.; Del Rio-Tsonis, Katia

2013-01-01

Identifying the initiation signals for tissue regeneration in vertebrates is one of the major challenges in regenerative biology. Much of the research thus far has indicated that certain growth factors have key roles. Here we show that complement fragment C3a is sufficient to induce complete regeneration of the embryonic chick retina from stem/progenitor cells present in the eye, independent of fibroblast growth factor receptor signaling. Instead, C3a induces retina regeneration via STAT3 activation, which in turn activates the injury- and inflammation-responsive factors, IL-6, IL-8 and TNF-α. This activation sets forth regulation of Wnt2b, Six3 and Sox2, genes associated with retina stem and progenitor cells. Thus, our results establish a mechanism for retina regeneration based on injury and inflammation signals. Furthermore, our results indicate a unique function for complement anaphylatoxins that implicate these molecules in the induction and complete regeneration of the retina, opening new avenues of experimentation in the field. PMID:23942241

COMPARISON OF RNFL THICKNESS AND VISUAL FIELD CHANGES BETWEEN DIABETIC WITHOUT RETINOPATHY AND NONDIABETIC CONTROLS- A CROSS-SECTIONAL STUDY

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Soumya Swarup Chattopadhyay

2017-10-01

Full Text Available BACKGROUND Diabetes mellitus is one of the major component of metabolic syndrome and a leading cause of ocular morbidity in modern era and India will be considered to be the diabetes capital of the world. Before the onset of diabetic retinopathy, other structural and functional changes may predict the visual diminution of the individual. MATERIALS AND METHODS In this cross-sectional study in a tertiary care hospital, after inclusion and exclusion, the age-gender matched groups (diagnosed type 2 diabetes patients without diabetic retinopathy and controls without diabetes were thoroughly examined clinically and by noninvasive and invasive examination (after proper counselling of the patient and informed consent. Then, they are tested for functional loss of retina by Humphrey FDT, GDx VCC. Comparison done between cases and controls as well as poorly-controlled and well-controlled diabetic groups. RESULTS It was found that the average RNFL thickness was significantly reduced in diabetics (mean 53.48, SD 2.69 compared to controls (mean 60.21, SD 1.87 (p7%, the RNFL thickness was significantly reduced (mean 52.23, SD 1.31 compared to diabetics with good metabolic control (mean 56.38, SD 2.92 (p<0.05. In retinal functional testing, it was found that the Humphrey FDT mean deviation (FDT MD and pattern standard deviation (FDT PSD were significantly worse in diabetics (FDT MD- 1.478, SD 0.386, (FDT PSD- 3.485, SD 0.403 compared to normal controls (FDT MD- 0.442, SD 0.536, (FDT PSD- 1.438, SD 0.404. The parameters were also found to be significantly worse in uncontrolled diabetics (p<0.05. CONCLUSION To conclude, without diabetic retinopathy, functional and structural loss in retina in diabetes patients compared to age-sex matched individual and especially in poorly-controlled diabetes should be of concern as there are no detectable vasculopathy. So, early diagnosis and control of diabetes is advocated to control this functional loss

Addition of Adapted Optics towards obtaining a quantitative detection of diabetic retinopathy

Science.gov (United States)

Yust, Brian; Obregon, Isidro; Tsin, Andrew; Sardar, Dhiraj

2009-04-01

An adaptive optics system was assembled for correcting the aberrated wavefront of light reflected from the retina. The adaptive optics setup includes a superluminous diode light source, Hartmann-Shack wavefront sensor, deformable mirror, and imaging CCD camera. Aberrations found in the reflected wavefront are caused by changes in the index of refraction along the light path as the beam travels through the cornea, lens, and vitreous humour. The Hartmann-Shack sensor allows for detection of aberrations in the wavefront, which may then be corrected with the deformable mirror. It has been shown that there is a change in the polarization of light reflected from neovascularizations in the retina due to certain diseases, such as diabetic retinopathy. The adaptive optics system was assembled towards the goal of obtaining a quantitative measure of onset and progression of this ailment, as one does not currently exist. The study was done to show that the addition of adaptive optics results in a more accurate detection of neovascularization in the retina by measuring the expected changes in polarization of the corrected wavefront of reflected light.

Training and professional profile of retinologists in Spain: Retina 2 project, Report 4.

Science.gov (United States)

Pastor, J Carlos; Fernández, Itziar; Rojas, Jimena; Coco, Rosa; Sanabria, Maria R; Rodríguez-de la Rúa, Enrique; Sánchez, Diego; Valverde, Carmen; Sala-Puigdollers, Anna

2011-01-01

Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties. After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined. Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%). Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5%) practiced anterior segment surgery, and 78.7% declared skills in vitrectomy. We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.

Automatic detection of blood vessels in retinal images for diabetic retinopathy diagnosis.

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Raja, D Siva Sundhara; Vasuki, S

2015-01-01

Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients. DR is mainly caused due to the damage of retinal blood vessels in the diabetic patients. It is essential to detect and segment the retinal blood vessels for DR detection and diagnosis, which prevents earlier vision loss in diabetic patients. The computer aided automatic detection and segmentation of blood vessels through the elimination of optic disc (OD) region in retina are proposed in this paper. The OD region is segmented using anisotropic diffusion filter and subsequentially the retinal blood vessels are detected using mathematical binary morphological operations. The proposed methodology is tested on two different publicly available datasets and achieved 93.99% sensitivity, 98.37% specificity, 98.08% accuracy in DRIVE dataset and 93.6% sensitivity, 98.96% specificity, and 95.94% accuracy in STARE dataset, respectively.

[Results of the use of antioxidant and angioprotective agents in type 2 diabetes patients with diabetic retinopathy and age-related macular degeneration].

Science.gov (United States)

Moshetova, L K; Vorob'eva, I V; Alekseev, I B; Mikhaleva, L G

2015-01-01

to investigate changes in clinical, functional, and morphological parameters of the retina in type 2 diabetes patients with diabetic retinopathy (DR) and those with combined fundus pathology (DR plus age-related macular degeneration (AMD)) before and after a course of antioxidants and angioprotectors in the form of mono- or combination therapy. The study included 180 patients (180 eyes) with type 2 diabetes divided into 6 groups of 30 each. DR was graded according to E. Kohner and M. Porta classification, AMD--AREDS classification. Thus, group 1 consisted of patients with DRO,; group 2--DR1 without DM, group 3--DR1 with DM, group 4--DRO and "dry" AMD (AREDS 1-3), group 5--DR1 with no DM but with AMD (AREDS 1-3), and group 6--DR1 with DM and AMD (AREDS 1-3). A drug containing lutein 6 mg, zeaxanthin 0.5 mg, vitamin C 60 mg, vitamin E 7 mg, vitamin A 1.5 mg, vitamin B2 1.2 mg, rutin 25 mg, zinc 5 mg, selenium 25 mcg, and bilberry extract 60 mg was used for antioxidative therapy. Ginkgo biloba leaf extract 60 mg was chosen as the angioprotector. In all patients visual acuity, macular thickness and morphology (OCT) as well as light sensitivity (microperimetry) were assessed before and after the treatment course. Analysis of baseline measurements demonstrated a significant decrease in best corrected visual acuity (p Macular thickness was increased in all groups, however, the changes were statistically significant only in groups 3 and 6 (pmacular thickness decreased in all groups, however, the changes were statistically significant (p prevention, and early treatment. Conservative treatment with antioxidant and angioprotective agents has been proved effective in type 2 diabetes patients with preclinical (DRO) and early (DR1) diabetic retinopathy and those with DR and "dry" AMD (AREDS 1-3) in terms of functional and morphological parameters of the retina. From all the regimens, a combined antioxidant and double-dose angioprotective (240 mg) therapy appeared to be the most

Human Genetics of Diabetic Retinopathy: Current Perspectives

Directory of Open Access Journals (Sweden)

Daniel P. K. Ng

2010-01-01

Full Text Available Diabetic retinopathy (DR is a most severe microvascular complication which, if left unchecked, can be sight-threatening. With the global prevalence of diabetes being relentlessly projected to rise to 438 million subjects by 2030, DR will undoubtedly pose a major public health concern. Efforts to unravel the human genetics of DR have been undertaken using the candidate gene and linkage approaches, while GWAS efforts are still lacking. Aside from evidence for a few genes including aldose reductase and vascular endothelial growth factor, the genetics of DR remain poorly elucidated. Nevertheless, the promise of impactful scientific discoveries may be realized if concerted and collaborative efforts are mounted to identify the genes for DR. Harnessing new genetic technologies and resources such as the upcoming 1000 Genomes Project will help advance this field of research, and potentially lead to a rich harvest of insights into the biological mechanisms underlying this debilitating complication.

Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

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Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

2015-06-01

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

Detection of retinal capillary nonperfusion in fundus fluorescein angiogram of diabetic retinopathy.

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Rasta, Seyed Hossein; Nikfarjam, Shima; Javadzadeh, Alireza

2015-01-01

Retinal capillary nonperfusion (CNP) is one of the retinal vascular diseases in diabetic retinopathy (DR) patients. As there is no comprehensive detection technique to recognize CNP areas, we proposed a different method for computing detection of ischemic retina, non-perfused (NP) regions, in fundus fluorescein angiogram (FFA) images. Whilst major vessels appear as ridges, non-perfused areas are usually observed as ponds that are surrounded by healthy capillaries in FFA images. A new technique using homomorphic filtering to correct light illumination and detect the ponds surrounded in healthy capillaries on FFA images was designed and applied on DR fundus images. These images were acquired from the diabetic patients who had referred to the Nikookari hospital and were diagnosed for diabetic retinopathy during one year. Our strategy was screening the whole image with a fixed window size, which is small enough to enclose areas with identified topographic characteristics. To discard false nominees, we also performed a thresholding operation on the screen and marked images. To validate its performance we applied our detection algorithm on 41 FFA diabetic retinopathy fundus images in which the CNP areas were manually delineated by three clinical experts. Lesions were found as smooth regions with very high uniformity, low entropy, and small intensity variations in FFA images. The results of automated detection method were compared with manually marked CNP areas so achieved sensitivity of 81%, specificity of 78%, and accuracy of 91%.The result was present as a Receiver operating character (ROC) curve, which has an area under the curve (AUC) of 0.796 with 95% confidence intervals. This technique introduced a new automated detection algorithm to recognize non-perfusion lesions on FFA. This has potential to assist detecting and managing of ischemic retina and may be incorporated into automated grading diabetic retinopathy structures.

Canonical Wnt signaling in diabetic retinopathy.

Science.gov (United States)

Chen, Qian; Ma, Jian-Xing

2017-10-01

Diabetic retinopathy (DR) is a common eye complication of diabetes, and the pathogenic mechanism of DR is still under investigation. The canonical Wnt signaling pathway is an evolutionarily conserved pathway that plays fundamental roles in embryogenesis and adult tissue homeostasis. Wnt signaling regulates expression of multiple genes that control retinal development and eye organogenesis, and dysregulated Wnt signaling plays pathophysiological roles in many ocular diseases, including DR. This review highlights recent progress in studies of Wnt signaling in DR. We discuss Wnt signaling regulation in the retina and dysregulation of Wnt signaling associated with ocular diseases with an emphasis on DR. We also discuss the therapeutic potential of modulating Wnt signaling in DR. Continued studies in this field will advance our current understanding on DR and contribute to the development of new treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Image Signal Transfer Method in Artificial Retina using Laser

Energy Technology Data Exchange (ETDEWEB)

Yoon, I.Y.; Lee, B.H.; Kim, S.J. [Seoul National University, Seoul (Korea)

2002-05-01

Recently, the research on artificial retina for the blind is active. In this paper a new optical link method for the retinal prosthesis is proposed. Laser diode system was chosen to transfer image into the eye in this project and the new optical system was designed and evaluated. The use of laser diode array in artificial retina system makes system simple for lack of signal processing part inside of the eyeball. Designed optical system is enough to focus laser diode array on photodiode array in 20X20 application. (author). 11 refs., 7 figs., 2 tabs.

Role of endoplasmic reticulum stress in 12/15-lipoxygenase-induced retinal microvascular dysfunction in a mouse model of diabetic retinopathy.

Science.gov (United States)

Elmasry, Khaled; Ibrahim, Ahmed S; Saleh, Heba; Elsherbiny, Nehal; Elshafey, Sally; Hussein, Khaled A; Al-Shabrawey, Mohamed

2018-05-01

Our earlier studies have established the role of 12/15-lipoxygenase (LO) in mediating the inflammatory reaction in diabetic retinopathy. However, the exact mechanism is still unclear. The goal of the current study was to identify the potential role of endoplasmic reticulum (ER) stress as a major cellular stress response in the 12/15-LO-induced retinal changes in diabetic retinopathy. We used in vivo and in vitro approaches. For in vivo studies, experimental diabetes was induced in wild-type (WT) mice and 12/15-Lo (also known as Alox15) knockout mice (12/15-Lo -/- ); ER stress was then evaluated after 12-14 weeks of diabetes. We also tested the effect of intravitreal injection of 12-hydroxyeicosatetraenoic acid (HETE) on retinal ER stress in WT mice and in mice lacking the catalytic subunit of NADPH oxidase, encoded by Nox2 (also known as Cybb) (Nox2 -/- mice). In vitro studies were performed using human retinal endothelial cells (HRECs) treated with 15-HETE (0.1 μmol/l) or vehicle, with or without ER stress or NADPH oxidase inhibitors. This was followed by evaluation of ER stress response, NADPH oxidase expression/activity and the levels of phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) by western blotting and immunoprecipitation assays. Moreover, real-time imaging of intracellular calcium (Ca 2+ ) release in HRECs treated with or without 15-HETE was performed using confocal microscopy. Deletion of 12/15-Lo significantly attenuated diabetes-induced ER stress in mouse retina. In vitro, 15-HETE upregulated ER stress markers such as phosphorylated RNA-dependent protein kinase-like ER-regulated kinase (p-PERK), activating transcription factor 6 (ATF6) and protein disulfide isomerase (PDI) in HRECs. Inhibition of ER stress reduced 15-HETE-induced-leucocyte adhesion, VEGFR2 phosphorylation and NADPH oxidase expression/activity. However, inhibition of NADPH oxidase or deletion of Nox2 had no effect on ER stress induced by the 12/15-LO

HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration

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Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel

2011-01-01

Summary Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that proHB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals. PMID:22340497

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

Science.gov (United States)

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

2015-04-01

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

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

Science.gov (United States)

Yang, Xu; Gong, Bo; Lu, Jian-Wei

2015-01-01

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

Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

Science.gov (United States)

Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

2013-10-29

In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

Proteomic profiling of early degenerative retina of RCS rats.

Science.gov (United States)

Zhu, Zhi-Hong; Fu, Yan; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

2017-01-01

To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student's t -test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

Proteomic profiling of early degenerative retina of RCS rats

Directory of Open Access Journals (Sweden)

Zhi-Hong Zhu

2017-06-01

Full Text Available AIM: To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP. METHODS: Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs. Bioinformatics analyses, including Gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS: In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student’s t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION: We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

NETosis Delays Diabetic Wound Healing in Mice and Humans.

Science.gov (United States)

Fadini, Gian Paolo; Menegazzo, Lisa; Rigato, Mauro; Scattolini, Valentina; Poncina, Nicol; Bruttocao, Andrea; Ciciliot, Stefano; Mammano, Fabio; Ciubotaru, Catalin Dacian; Brocco, Enrico; Marescotti, Maria Cristina; Cappellari, Roberta; Arrigoni, Giorgio; Millioni, Renato; Vigili de Kreutzenberg, Saula; Albiero, Mattia; Avogaro, Angelo

2016-04-01

Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue. Therefore, we examined the effect of NETosis on the healing of diabetic foot ulcers (DFUs). Using proteomics, we found that NET components were enriched in nonhealing human DFUs. In an independent validation cohort, a high concentration of neutrophil elastase in the wound was associated with infection and a subsequent worsening of the ulcer. NET components (elastase, histones, neutrophil gelatinase-associated lipocalin, and proteinase-3) were elevated in the blood of patients with DFUs. Circulating elastase and proteinase-3 were associated with infection, and serum elastase predicted delayed healing. Neutrophils isolated from the blood of DFU patients showed an increased spontaneous NETosis but an impaired inducible NETosis. In mice, skin PAD4 activity was increased by diabetes, and FACS detection of histone citrullination, together with intravital microscopy, showed that NETosis occurred in the bed of excisional wounds. PAD4 inhibition by Cl-amidine reduced NETting neutrophils and rescued wound healing in diabetic mice. Cumulatively, these data suggest that NETosis delays DFU healing. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.

Science.gov (United States)

Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald

2009-03-01

Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

TOPOGRAPHIC ORGANIZATION AND SPECIALIZED AREAS IN THE RETINA OF Callopistes palluma: GANGLION CELL LAYER

OpenAIRE

Inzunza, Oscar; Barros B., Zitta; Bravo, Hermes

1998-01-01

In this paper we analyze the topographic distribution and cell body size of neurons (ganglion and displaced amacrine) of layer 8 of the retina in the chilean reptile Callopistes palluma; using whole mount retinaswith nissl stain. Callopistes palluma retina has an area centralis without fovea in which the ganglion cell density amounts 20.000 cells / µm2 while the displaced amacrine neurons is about 7.000 cells / µm2. This neural density decreased gradually towards the peripheral retina. A hor...

Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

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Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

2013-12-01

Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. �

Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

International Nuclear Information System (INIS)

Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

2013-01-01

Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. �

VEGF as a Survival Factor in Ex Vivo Models of Early Diabetic Retinopathy.

Science.gov (United States)

Amato, Rosario; Biagioni, Martina; Cammalleri, Maurizio; Dal Monte, Massimo; Casini, Giovanni

2016-06-01

Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR. Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants. Data were obtained with real-time RT-PCR, Western blot, ELISA, and immunohistochemistry. Apoptosis was induced in the retinal explants by HG, OS, or AGE treatments. At the same time, explants also showed increased VEGF expression and release. The data revealed that VEGF is released shortly after exposure of the explants to stressors and before the level of cell death reaches its maximum. Retinal cell apoptosis was inhibited by OCT and PACAP. At the same time, OCT and PACAP also reduced VEGF expression and release. Vascular endothelial growth factor turned out to be a protective factor for the stressed retinal explants, because inhibiting VEGF with a VEGF trap further increased cell death. These data show that protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. These observations suggest that the retina in early DR releases VEGF as a prosurvival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.

Current status in diabetic macular edema treatments

Institute of Scientific and Technical Information of China (English)

Pedro; Romero-Aroca

2013-01-01

Diabetes is a serious chronic condition,which increase the risk of cardiovascular diseases,kidney failure and nerve damage leading to amputation.Furthermore the ocular complications include diabetic macular edema,is the leading cause of blindness among adults in the industrialized countries.Today,blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy.The treatment should include an optimized control of glycemia,arterial tension,lipids and renal status.The photocoagulation laser is currently restricted to focal macular edema in some countries,but due the high cost of intravitreal drugs,the use of laser treatment for focal and diffuse diabetic macular edema(DME),can be valid as gold standard in many countries.The intravitreal anti vascular endothelial growth factor drugs(ranibizumab and bevacizumab),are indicated in the treatment of all types of DME,but the correct protocol for administration should be defined for the different Retina Scientific Societies.The corticosteroids for diffuse DME,has a place in pseudophakic patients,but its complications restricted the use of these drugs for some patients.Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.

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

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Xu Yang

2015-12-01

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

Podocytic PKC-alpha is regulated in murine and human diabetes and mediates nephrin endocytosis.

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Irini Tossidou

Full Text Available BACKGROUND: Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss of high molecular weight proteins in the urine is usually associated with decreased expression of slit diaphragm proteins. Nephrin, is the major component of the glomerular slit diaphragm and loss of nephrin has been well described in rodent models of experimental diabetes as well as in human diabetic nephropathy. METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we analyzed the role of PKC-alpha (PKCalpha on endocytosis of nephrin in podocytes. We found that treatment of diabetic mice with a PKCalpha-inhibitor (GO6976 leads to preserved nephrin expression and reduced proteinuria. In vitro, we found that high glucose stimulation would induce PKCalpha protein expression in murine and human podocytes. We can demonstrate that PKCalpha mediates nephrin endocytosis in podocytes and that overexpression of PKCalpha leads to an augmented endocytosis response. After PKC-activation, we demonstrate an inducible association of PKCalpha, PICK1 and nephrin in podocytes. Moreover, we can demonstrate a strong induction of PKCalpha in podocytes of patients with diabetic nephropathy. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that activation of PKCalpha is a pathomechanistic key event during the development of diabetic nephropathy. PKCalpha is involved in reduction of nephrin surface expression and therefore PKCalpha inhibition might be a novel target molecule for anti-proteinuric therapy.

Towards photovoltaic powered artificial retina

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Santiago Silvestre

2011-11-01

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

Simulated annealing in adaptive optics for imaging the eye retina

International Nuclear Information System (INIS)

Zommer, S.; Adler, J.; Lipson, S. G.; Ribak, E.

2004-01-01

Full Text:Adaptive optics is a method designed to correct deformed images in real time. Once the distorted wavefront is known, a deformable mirror is used to compensate the aberrations and return the wavefront to a plane wave. This study concentrates on methods that omit wave front sensing from the reconstruction process. Such methods use stochastic algorithms to find the extremum of a certain sharpness function, thereby correcting the image without any information on the wavefront. Theoretical work [l] has shown that the optical problem can be mapped onto a model for crystal roughening. The main algorithm applied is simulated annealing. We present a first hardware realization of this algorithm in an adaptive optics system designed to image the retina of the human eye

The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration.

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Patricia Bogdanov

Full Text Available BACKGROUND: To characterize the sequential events that are taking place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes (db/db mouse. METHODS: C57BLKsJ-db/db mice were used as spontaneous type 2 diabetic animal model, and C57BLKsJ-db/+ mice served as the control group. To assess the chronological sequence of the abnormalities the analysis was performed at different ages (8, 16 and 24 weeks. The retinas were evaluated in terms of morphological and functional abnormalities [electroretinography (ERG]. Histological markers of neurodegeneration (glial activation and apoptosis were evaluated by immunohistochemistry. In addition glutamate levels and glutamate/aspartate transporter (GLAST expression were assessed. Furthermore, to define gene expression changes associated with early diabetic retinopathy a transcriptome analyses was performed at 8 week. Furthermore, an additional interventional study to lower blood glucose levels was performed. RESULTS: Glial activation was higher in diabetic than in non diabetic mice in all the stages (p<0.01. In addition, a progressive loss of ganglion cells and a significant reduction of neuroretinal thickness were also observed in diabetic mice. All these histological hallmarks of neurodegeneration were less pronounced at week 8 than at week 16 and 24. Significant ERG abnormalities were present in diabetic mice at weeks 16 and 24 but not at week 8. Moreover, we observed a progressive accumulation of glutamate in diabetic mice associated with an early downregulation of GLAST. Morphological and ERG abnormalities were abrogated by lowering blood glucose levels. Finally, a dysregulation of several genes related to neurotransmission and oxidative stress such as UCP2 were found at week 8. CONCLUSIONS: Our results suggest that db/db mouse reproduce the features of the neurodegenerative process that occurs in the human diabetic eye. Therefore, it seems an appropriate model for investigating the

Training and professional profile of retinologists in Spain: Retina 2 project, Report 4

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Pastor JC

2011-04-01

Full Text Available J Carlos Pastor1,3, Itziar Fernández2, Jimena Rojas1, Rosa Coco1, Maria R Sanabria1, Enrique Rodríguez-de la Rúa1,3, Diego Sánchez3, Carmen Valverde3, Anna Sala Puigdollers1,31University Institute of Applied Ophthalmobiology (IOBA, Retina Group, 2Ministry of Science and Innovation CIBER-BBN, Statistics Department, 3Clinic University Hospital, University of Valladolid, Valladolid, SpainBackground: Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties.Methods: After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined.Results: Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%. Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5% practiced anterior segment surgery, and 78.7% declared skills in vitrectomy.Conclusion: We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.Keywords: clinical activity, fellowship, mastership, professional profile, retinologist training

Evaluation of the Zucker diabetic fatty (ZDF rat as a model for human disease based on urinary peptidomic profiles.

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Justyna Siwy

Full Text Available Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD and cardiovascular disease (CVD biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin or related to disease development (collagen. Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level.

The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

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I. V. Vorobyova

2014-10-01

Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

Directory of Open Access Journals (Sweden)

I. V. Vorobyova

2014-01-01

Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

64,000-Mr autoantigen in type I diabetes. Evidence against its surface location on human islets

International Nuclear Information System (INIS)

Colman, P.G.; Campbell, I.L.; Kay, T.W.; Harrison, L.C.

1987-01-01

The sera of type I (insulin-dependent) diabetic subjects are reported to contain autoantibodies against a 64,000-Mr protein identified in [ 35 S]methionine biosynthetically labeled pancreatic islet cells. We have attempted to localize this autoantigen to the surface of the beta-cell and to define its properties. Sera from 10 newly diagnosed type I diabetic subjects, including five of the index sera originally used to identify the autoantigen, were shown to specifically precipitate a reduced protein of 67,000 Mr from Triton-solubilized, surface 125 I-labeled cultured adult human islet and rat insulinoma (RINm5F) cells but not from fresh rat spleen cells. Further characterization revealed that this protein was bovine serum albumin (BSA) adsorbed to cells from fetal calf serum (FCS)-supplemented culture medium and precipitated by BSA antibodies present in many diabetic sera. No labeled proteins were specifically precipitated when surface 125 I-labeled and solubilized human islet or RINm5F cells were precleared with anti-BSA immunoglobulins or when cells were first cultured in human serum. In contrast, a 64,000-Mr protein, clearly not BSA, was precipitated by diabetic globulins from human islets but not from RINm5F cells labeled with [ 35 S]methionine. In addition, a protein of the same size as well as proteins of approximately 35,000, 43,000, 140,000, and 200,000 Mr were specifically precipitated by diabetic globulins from freshly isolated human islets solubilized in Triton X-100 and then labeled with 125 I. These findings suggest that the 64,000-Mr antigen is not expressed on the surface of human islet cells, at least in culture, and therefore question its relevance as a target for islet cell surface antibodies in initiating beta-cell damage

Sobre la terapia génica para enfermedades de la retina.

Science.gov (United States)

Fischer, M Dominik

2017-07-11

Las mutaciones en un gran número de genes provocan degeneración de la retina y ceguera sin que exista actualmente cura alguna. En las últimas décadas, la terapia génica para enfermedades de la retina ha evolucionado y se ha convertido en un nuevo y prometedor paradigma terapéutico para estas enfermedades poco comunes. Este artículo refleja las ideas y los conceptos que parten de la ciencia básica hacia la aplicabilidad de la terapia génica en el ámbito clínico. Se describen los avances y las reflexiones actuales sobre la eficacia de los ensayos clínicos en la actualidad y se discuten los posibles obstáculos y soluciones de cara al futuro de la terapia génica para enfermedades de la retina. © 2017 S. Karger AG, Basel.

Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Ruth E.Rosenstein; Diego C.Fernandez

2014-01-01

Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic reti-nopathy have focused either on highly speciifc therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resis-tance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging isch-emia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.

Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling.

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Bretón-Romero, Rosa; Feng, Bihua; Holbrook, Monika; Farb, Melissa G; Fetterman, Jessica L; Linder, Erika A; Berk, Brittany D; Masaki, Nobuyuki; Weisbrod, Robert M; Inagaki, Elica; Gokce, Noyan; Fuster, Jose J; Walsh, Kenneth; Hamburg, Naomi M

2016-03-01

Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus. © 2016 American Heart

Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

OpenAIRE

Henshaw, F. R.; Boughton, P.; Lo, L.; McLennan, S. V.; Twigg, S. M.

2015-01-01

Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1??g?rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulati...

Diabetic retinal pigment epitheliopathy: fundus autofluorescence and spectral-domain optical coherence tomography findings.

Science.gov (United States)

Kang, Eui Chun; Seo, Yuri; Byeon, Suk Ho

2016-10-01

To describe the characteristics of an unfamiliar disease entity, diabetic retinal pigment epitheliopathy (DRPE), using fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). This retrospective study included 17 eyes from 10 proliferative diabetic retinopathy (PDR) patients with granular hypo-autofluorescence and/or variable hyper-autofluorescence on FAF (DRPE group) and 17 eyes from 10 age- and sex-matched PDR patients without abnormal autofluorescence (PDR group). Eyes with diabetic macular edema were excluded. Visual acuity (VA), retinal thickness (RT), and choroidal thickness (CT) were compared between the groups. Eyes in the DRPE group had worse logMAR VA than eyes in the PDR group (0.369 ± 0.266 vs. 0.185 ± 0.119; P = 0.026). The thickness of the retinal pigment epithelium plus the inner segment/outer segment of the photoreceptors was reduced to a greater degree in the DRPE group than the PDR group (P retina showed no differences between the two groups. CT was significantly thicker in the DRPE group than in the PDR group (329.00 ± 33.76 vs. 225.62 ± 37.47 μm; P retina, and thicker choroid in comparison with eyes with PDR. Alterations of autofluorescence on FAF and changes in the outer retinal thickness and CT on SD-OCT can be helpful for differentiating DRPE in patients with PDR.

Optimal wavelet transform for the detection of microaneurysms in retina photographs.

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Quellec, Gwénolé; Lamard, Mathieu; Josselin, Pierre Marie; Cazuguel, Guy; Cochener, Béatrice; Roux, Christian

2008-09-01

In this paper, we propose an automatic method to detect microaneurysms in retina photographs. Microaneurysms are the most frequent and usually the first lesions to appear as a consequence of diabetic retinopathy. So, their detection is necessary for both screening the pathology and follow up (progression measurement). Automating this task, which is currently performed manually, would bring more objectivity and reproducibility. We propose to detect them by locally matching a lesion template in subbands of wavelet transformed images. To improve the method performance, we have searched for the best adapted wavelet within the lifting scheme framework. The optimization process is based on a genetic algorithm followed by Powell's direction set descent. Results are evaluated on 120 retinal images analyzed by an expert and the optimal wavelet is compared to different conventional mother wavelets. These images are of three different modalities: there are color photographs, green filtered photographs, and angiographs. Depending on the imaging modality, microaneurysms were detected with a sensitivity of respectively 89.62%, 90.24%, and 93.74% and a positive predictive value of respectively 89.50%, 89.75%, and 91.67%, which is better than previously published methods.

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

Science.gov (United States)

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

2017-04-01

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

Placental Growth Factor Contributes to Micro-Vascular Abnormalization and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

Science.gov (United States)

Kowalczuk, Laura; Touchard, Elodie; Omri, Samy; Jonet, Laurent; Klein, Christophe; Valamanes, Fatemeh; Berdugo, Marianne; Bigey, Pascal; Massin, Pascale; Jeanny, Jean-Claude; Behar-Cohen, Francine

2011-01-01

Objective There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1). Materials and Methods pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis. Results After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation. Conclusion This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease. PMID:21408222

Adaptive colour contrast coding in the salamander retina efficiently matches natural scene statistics.

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Genadiy Vasserman

Full Text Available The visual system continually adjusts its sensitivity to the statistical properties of the environment through an adaptation process that starts in the retina. Colour perception and processing is commonly thought to occur mainly in high visual areas, and indeed most evidence for chromatic colour contrast adaptation comes from cortical studies. We show that colour contrast adaptation starts in the retina where ganglion cells adjust their responses to the spectral properties of the environment. We demonstrate that the ganglion cells match their responses to red-blue stimulus combinations according to the relative contrast of each of the input channels by rotating their functional response properties in colour space. Using measurements of the chromatic statistics of natural environments, we show that the retina balances inputs from the two (red and blue stimulated colour channels, as would be expected from theoretical optimal behaviour. Our results suggest that colour is encoded in the retina based on the efficient processing of spectral information that matches spectral combinations in natural scenes on the colour processing level.

The Retina Algorithm

CERN Multimedia

CERN. Geneva; PUNZI, Giovanni

2015-01-01

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

Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1 in human type 2 diabetes

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Yoon Kun-Ho

2002-04-01

Full Text Available Abstract Background It has become increasingly clear that β-cell failure plays a critical role in the pathogenesis of type 2 diabetes. Free-radical mediated β-cell damage has been intensively studied in type 1 diabetes, but not in human type 2 diabetes. Therefore, we studied the protein expression of the DNA repair enzyme Ogg1 in pancreases from type 2 diabetics. Ogg1 was studied because it is the major enzyme involved in repairing 7,8-dihydro-8-oxoguanosine DNA adducts, a lesion previously observed in a rat model of type 2 diabetes. Moreover, in a gene expression screen, Ogg1 was over-expressed in islets from a human type 2 diabetic. Methods Immunofluorescent staining of Ogg1 was performed on pancreatic specimens from healthy controls and patients with diabetes for 2–23 years. The intensity and islet area stained for Ogg1 was evaluated by semi-quantitative scoring. Results Both the intensity and the area of islet Ogg1 staining were significantly increased in islets from the type 2 diabetic subjects compared to the healthy controls. A correlation between increased Ogg1 fluorescent staining intensity and duration of diabetes was also found. Most of the staining observed was cytoplasmic, suggesting that mitochondrial Ogg1 accounts primarily for the increased Ogg1 expression. Conclusion We conclude that oxidative stress related DNA damage may be a novel important factor in the pathogenesis of human type 2 diabetes. An increase of Ogg1 in islet cell mitochondria is consistent with a model in which hyperglycemia and consequent increased β-cell oxidative metabolism lead to DNA damage and the induction of Ogg1 expression.

Glycinergic pathways in the goldfish retina

International Nuclear Information System (INIS)

Marc, R.E.; Lam, D.M.

1981-01-01

Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish has been used to study some anatomical and physiological properties of potentially glycinergic neurons. There are two classes of retinal cells exhibiting high affinity glycine uptake: Aa amacrine cells and I2 interplexiform cells. Aa amacrine cells constitute about 20% of the somas in the amacrine cell layer and send their dendrites to the middle of the inner plexiform layer. There they are both pre- and postsynaptic primarily to other amacrine cells. Photic modulation of glycine uptake indicates that they are probably red-hyperpolarizing/green-depolarizing neurons. I2 interplexiform cells are a newly discovered type of interplexiform cell; in the outer plexiform layer, they receive direct synaptic input from the somas of red-dominated GABAergic H1 horizontal cells and are apparently presynaptic to dendrites of unidentified types of horizontal cells. The connections of I2 interplexiform cells have not been successfully characterized in the inner plexiform layer. These findings extend our knowledge of neurochemically specific pathways in the cyprinid retina and indicate that glycine, like GABA, is a neurotransmitter primarily involved with circuits coding ''red'' information

Human and rodent muscle Na(+)-K(+)-ATPase in diabetes related to insulin, starvation, and training

DEFF Research Database (Denmark)

Schmidt, T A; Hasselbalch, S; Farrell, P A

1994-01-01

cerebral cortex Na(+)-K(+)-ATPase concentration as a result of diabetes, semistarvation, or insulin treatment. In human subjects, Na(+)-K(+)-ATPase concentration in vastus lateralis muscle biopsies was 17 and 22% greater (P dependent diabetes...... mellitus (n = 24) and insulin-dependent diabetes mellitus (n = 7) than in control subjects (n = 8). A positive linear correlation between muscle Na(+)-K(+)-ATPase and plasma insulin concentrations was observed (r = 0.50, P = 0.006; n = 29). Thus, insulin seems a regulator of muscle Na......(+)-K(+)-ATPase concentration, reduction of muscle Na(+)-K(+)-ATPase concentration with untreated diabetes bears similarities with undernourishment, and physical conditioning may ameliorate the muscle Na(+)-K(+)-ATPase concentration decrease induced by diabetes....

Atrofia girata de coróide e retina : relato de caso

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Oyamaguchi Emerson Kenji

2003-01-01

Full Text Available OBJETIVO: Relatar um caso de atrofia girata de coróide e retina com confirmação por meio da bioquímica do plasma. MÉTODO: Aferiu-se a melhor acuidade visual corrigida de ambos olhos (AO em tabela de Snellen. Foram realizados biomicroscopia do segmento anterior, refração, mapeamento de retina, angiografia fluoresceínica, campo visual e dosagem da ornitina sérica (aminoacidograma. RESULTADOS: Paciente de 22 anos, sexo feminino, cor branca, apresentando alta miopia e acuidade visual (AV 20/100 em AO. À biomicroscopia do segmento anterior apresentava catarata subcapsular posterior em AO. À oftalmoscopia foram verificadas lesões atróficas da coróide e da retina bem delimitadas em meia periferia de AO. O aminoacidograma constatou elevação correspondente ao complexo da ornitina. CONCLUSÃO: Relata-se um caso típico de atrofia girata, distrofia retiniana rara associada a hiperornitinemia.

Current Advances in Pharmacotherapy and Technology for Diabetic Retinopathy: A Systematic Review

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Lei Lu

2018-01-01

Full Text Available Diabetic retinopathy (DR is classically defined by its vascular lesions and damage in the neurons of the retina. The cellular and clinical elements of DR have many features of chronic inflammation. Understanding the individual cell-specific inflammatory changes in the retina may lead to novel therapeutic approaches to prevent vision loss. The systematic use of available pharmacotherapy has been reported as a useful adjunct tool to laser photocoagulation, a gold standard therapy for DR. Direct injections or intravitreal anti-inflammatory and antiangiogenesis agents are widely used pharmacotherapy to effectively treat DR and diabetic macular edema (DME. However, their effectiveness is short term, and the delivery system is often associated with adverse effects, such as cataract and increased intraocular pressure. Further, systemic agents (particularly hypoglycemic, hypolipidemic, and antihypertensive agents and plants-based drugs have also provided promising treatment in the progression of DR. Recently, advancements in pluripotent stem cells technology enable restoration of retinal functionalities after transplantation of these cells into animals with retinal degeneration. This review paper summarizes the developments in the current and potential pharmacotherapy and therapeutic technology of DR. Literature search was done on online databases, PubMed, Google Scholar, clinitrials.gov, and browsing through individual ophthalmology journals and leading pharmaceutical company websites.

Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

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Sang Soo Kim

Full Text Available We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2 in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2 and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2 generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. The streptozotocin (STZ murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold. Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively.The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal

Effects of the photodynamic therapy on microbial reduction of diabetic ulcers in humans

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Carrinho Aureliano, Patrícia Michelassi; Andreani, Dora Inés. Kozusny; Morete, Vislaine de Aguiar; Iseri Giraldeli, Shizumi; Baptista, Alessandra; Navarro, Ricardo Scarparo; Villaverde, Antonio Balbin

2018-02-01

Diabetes Mellitus is a chronic disease that can lead to lower-limb ulceration. The photodynamic therapy (PDT) is based on light interaction with a photosensitizer capable to promote bacterial death and tissue repair acceleration. This study analyzed the effects of PDT in the repair of human diabetic ulcers, by means of microbiological assessment. The clinical study was composed of 12 patients of both sexes with diabetic ulcers in lower limbs that were divided into two groups, control group (n=6) and PDT group (n=6). All patients were treated with collagenase/chloramphenicol during the experimental period, in which 6 of them have received PDT with methylene blue dye (0.01%) associated with laser therapy (660 nm), dose of 6 J/cm2¨ and 30 mW laser power. PDT group received ten treatment sessions. Wounds were evaluated for micro-organisms analysis. It was found a reduction in the occurrence of Staphylococcus aureus in both groups, being that reduction more pronounced in the PDT group. Microbial count was performed on PDT group, showing a statistical difference reduction (p<0.05) when compared before and after the treatment. It is concluded that PDT seems to be effective in microbial reduction of human diabetic wounds, promoting acceleration and improvement of tissue repair quality.ty.

SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy

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Wang, Xiaoxin X.; Levi, Jonathan; Luo, Yuhuan; Myakala, Komuraiah; Herman-Edelstein, Michal; Qiu, Liru; Wang, Dong; Peng, Yingqiong; Grenz, Almut; Lucia, Scott; Dobrinskikh, Evgenia; D'Agati, Vivette D.; Koepsell, Hermann; Kopp, Jeffrey B.; Rosenberg, Avi Z.; Levi, Moshe

2017-01-01

There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. The second aim of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin, and urinary thiobarbituric acid-reacting substances. SGLT2 inhibition prevented renal lipid accumulation via inhibition of carbohydrate-responsive element-binding protein-β, pyruvate kinase L, SCD-1, and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation and expression of p65, TLR4, MCP-1, and osteopontin. These effects were associated with reduced mesangial expansion, accumulation of the extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice. PMID:28196866

Linezolid-induced optic neuropathy with a rare pathological change in the inner retina.

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Ishii, Nobuhito; Kinouchi, Reiko; Inoue, Masatomo; Yoshida, Akitoshi

2016-12-01

We report a case of linezolid-induced optic neuropathy with transient microcystic spaces in the inner retina. We observed the retina using Fourier-domain optical coherence tomography (FD-OCT) in a patient with linezolid-induced optic neuropathy. A 49-year-old woman presented to our department with a 1-week history of bilateral photophobia. At the first visit, her best-corrected visual acuity (VA) was 0.6 in the right eye and 0.5 in the left eye. She had moderate optic disk edema and central scotomas bilaterally. FD-OCT showed bilateral microcystic spaces in the retina. Microcystic spaces were seen in the retinal nerve fiber layer (RNFL) and at the border of the RNFL and the retinal ganglion cell layer. Magnetic resonance imaging and laboratory tests showed no positive findings except for an elevated lactic acid level. One week after the first visit, the VA levels decreased to 0.06 and 0.07 in the right and left eyes, respectively. Because the patient had a 7-month history of linezolid treatment for persistent pyogenic arthritis, we suspected linezolid-induced optic neuropathy and immediately terminated treatment with this drug. The optic disk edema and the microcystic spaces in the retina resolved, and the VA improved to 1.2 at 6 weeks after linezolid withdrawal. Microcystic spaces, which resolved with linezolid withdrawal, were observed in linezolid-induced optic neuropathy. The microcystic spaces in the inner retina can be the first retinal sign of some optic neuropathies.

Comparative proteomic analyses of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis).

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Okamoto, Haru; Umeda, Shinsuke; Nozawa, Takehiro; Suzuki, Michihiro T; Yoshikawa, Yasuhiro; Matsuura, Etsuko T; Iwata, Takeshi

2010-01-01

The central region of the primate retina is called the macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create a neural network adapted for high visual acuity. Damage to the fovea, e.g., by macular dystrophies and age-related macular degeneration, can reduce central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in the macula which differ from those in the peripheral retina in expression level. To investigate whether the distribution of proteins in the macula is different from the peripheral retina, proteomic analyses of tissues from these two regions of cynomolgus monkeys were compared. Two-dimensional gel electrophoresis and mass spectrometry identified 26 proteins that were present only in the macular gel spots. The expression levels of five proteins, cone photoreceptor specific arrestin-C, gamma-synuclein, epidermal fatty acid binding protein, tropomyosin 1alpha chain, and heterogeneous nuclear ribonucleoproteins A2/B1, were significantly higher in the macula than in the peripheral retina. Immunostaining of macula sections by antibodies to each identified protein revealed unique localization in the retina, retinal pigment epithelial cells and the choroidal layer. Some of these proteins were located in cells with higher densities in the macula. We suggest that it will be important to study these proteins to determine their contribution to the pathogenesis and progression of macula diseases.

Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics.

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Melton, Douglas A

2016-01-01

Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes. © 2016 Elsevier Inc. All rights reserved.

Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy.

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Wessel, Matthew M; Aaker, Grant D; Parlitsis, George; Cho, Minhee; D'Amico, Donald J; Kiss, Szilárd

2012-04-01

To evaluate patients with diabetic retinopathy using ultra-wide-field fluorescein angiography and to compare the visualized retinal pathology with that seen on an overly of conventional 7 standard field (7SF) imaging. Two hundred and eighteen eyes of 118 diabetic patients who underwent diagnostic fluorescein angiography using the Optos Optomap Panoramic 200A imaging system were included. The visualized area of the retina, retinal nonperfusion, retinal neovascularization, and panretinal photocoagulation were quantified by two independent masked graders. The respective areas identified on the ultra-wide-field fluorescein angiography image were compared with an overly of a modified 7SF image as outlined in the Early Treatment Diabetic Retinopathy Study. Ultra-wide-field fluorescein angiograms imaging, on average, demonstrated 3.2 times more total retinal surface area than 7SF. When compared with 7SF, ultra-wide-field fluorescein angiography showed 3.9 times more nonperfusion (P diabetic retinopathy. Improved retinal visualization may alter the classification of diabetic retinopathy and may therefore influence follow-up and treatment of these patients.

In Silico Ocular Pharmacokinetic Modeling: Delivery of Topical FK962 to Retina.

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Mori, Ayumi; Yabuta, Chiho; Kishimoto, Yayoi; Kozai, Seiko; Ohtori, Akira; Shearer, Thomas R; Azuma, Mitsuyoshi

2017-09-01

To establish the in silico ocular pharmacokinetic modeling for eye drops, and to simulate the dose regimen for FK962 in human choroid/retinal diseases. Pharmacokinetics for FK962 in vivo was performed by a single instillation of drops containing 0.1% 14 C-FK962 in rabbit eyes. Permeation of FK962 across the cornea, sclera, and choroid/retina was measured in vitro. Neurite elongation by FK962 was measured in cultured rat retinal ganglion cells. Parameters from the experimental data were used in an improved in silico model of ocular pharmacokinetics of FK962 in man. The mean concentration of FK962 in ocular tissues predicted by in silico modeling was consistent with in vivo results, validating the in silico model. FK962 rapidly penetrated into the anterior and posterior segments of the eye and then diffused into the vitreous body. The in silico pharmacokinetic modeling also predicted that a dose regimen of 0.0054% FK962 twice per day would produce biologically effective concentrations of FK962 in the choroid/retina, where FK962 facilitates rat neurite elongation. Our in silico model for ocular pharmacokinetics is useful (1) for predicting drug concentrations in specific ocular tissues after topical instillation, and (2) for suggesting the optimal dose regimens for eye drops. The pharmacodynamics for FK962 produced by this model may be useful for clinical trials against retinal neuropathy.

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

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Michael W Stuck

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

Effects of mercury intoxication on the response of horizontal cells of the retina of thraira fish (Hoplias malabaricus

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C.L. Tanan

2006-07-01

Full Text Available Methyl mercury (MeHg is highly neurotoxic, affecting visual function in addition to other central nervous system functions. The effect of mercury intoxication on the amplitude of horizontal cell responses to light was studied in the retina of the fish Hoplias malabaricus. Intracellular responses were recorded from horizontal cells of fish previously intoxicated with MeHg by intraperitoneal injection (IP group or by trophic exposure (T group. Only one retina per fish was used. The doses of MeHg chloride administered to the IP group were 0.01, 0.05, 0.1, 1.0, 2.0, and 6.0 mg/kg. The amplitudes of the horizontal cell responses were lower than control in individuals exposed to 0.01 (N = 4 retinas, 0.05 (N = 2 retinas and 0.1 mg/kg (N = 1 retina, whereas no responses were recorded in the 1.0, 2.0, and 6.0 mg/kg groups. T group individuals were fed young specimens of Astyanax sp previously injected with MeHg corresponding to 0.75 (N = 1 retina, 0.075 (N = 8 retinas or 0.0075 (N = 4 retinas mg/kg fish body weight. After 14 doses, one every 5 days, the amplitude of the horizontal cell response was higher than control in individuals exposed to 0.075 and 0.0075 mg/kg, and lower in individuals exposed to 0.75 mg/kg. We conclude that intoxication with MeHg affects the electrophysiological response of the horizontal cells in the retina, either reducing or increasing its amplitude compared to control, and that these effects are related to the dose and/or to the mode of administration.

Quality Enhancement and Nerve Fibre Layer Artefacts Removal in Retina Fundus Images by Off Axis Imaging

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Giancardo, Luca [ORNL; Meriaudeau, Fabrice [ORNL; Karnowski, Thomas Paul [ORNL; Li, Yaquin [University of Tennessee, Knoxville (UTK); Tobin Jr, Kenneth William [ORNL; Chaum, Edward [University of Tennessee, Knoxville (UTK)

2011-01-01

Retinal fundus images acquired with non-mydriatic digital fundus cameras are a versatile tool for the diagnosis of various retinal diseases. Because of the ease of use of newer camera models and their relative low cost, these cameras are employed worldwide by retina specialists to diagnose diabetic retinopathy and other degenerative diseases. Even with relative ease of use, the images produced by these systems sometimes suffer from reflectance artefacts mainly due to the nerve fibre layer (NFL) or other camera lens related reflections. We propose a technique that employs multiple fundus images acquired from the same patient to obtain a single higher quality image without these reflectance artefacts. The removal of bright artefacts, and particularly of NFL reflectance, can have great benefits for the reduction of false positives in the detection of retinal lesions such as exudate, drusens and cotton wool spots by automatic systems or manual inspection. If enough redundant information is provided by the multiple images, this technique also compensates for a suboptimal illumination. The fundus images are acquired in straightforward but unorthodox manner, i.e. the stare point of the patient is changed between each shot but the camera is kept fixed. Between each shot, the apparent shape and position of all the retinal structures that do not exhibit isotropic reflectance (e.g. bright artefacts) change. This physical effect is exploited by our algorithm in order to extract the pixels belonging to the inner layers of the retina, hence obtaining a single artefacts-free image.

Protective effects of tea, red wine and cocoa in diabetes. Evidences from human studies.

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Martin, Maria Angeles; Goya, Luis; Ramos, Sonia

2017-11-01

Prevention of diabetes through the diet has recently received an increasing interest, and polyphenolic compounds, such as flavanols, have become important potential chemopreventive natural agents due to their proved benefits on health, with low toxicity and cost. Tea, red wine and cocoa are good sources of flavanols and these highly consumed foods might contribute to prevent diabetes. In this regard, there is increasing evidence for a protective effect of tea, red wine and cocoa consumption against this disorder. This review summarizes the available epidemiological and interventional human studies providing evidence for and against this effect. Overall observational data suggest a benefit, but results are still equivocal and likely confounded by lifestyle and background dietary factors. The weight of data indicate favourable effects on diabetes risk factors for tea, red wine and cocoa intake, and a number of plausible mechanisms have been elucidated in human studies. However, despite the growing evidence it remains uncertain whether tea, red wine and cocoa consumption should be recommended to the general population or to patients as a strategy to reduce the risk of diabetes. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Diabetic retinopathy: pathogenesis and therapeutic implications].

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Pelikánová, Terezie

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increase in polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other epigenetic, metabolic and haemodynamic factors, including hypertension, dyslipidemia and oxidative stress. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, proinflammatory cytokines, vasoactive molecules, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant pattern, and finally in angiogenesis and tissue remodelling. Brain, liver, adipose tissue, GUT, skeletal muscle and other tissues could be another source of mediators. Therapeutic approaches used for patients with or at risk for diabetic retinopathy include drug therapy to reduce modifiable risk factors, laser photocoagulation, intravitreous administration of anti-VEGF agents/steroids and intraocular surgery. Screening plays an important role in early detection and intervention to prevent the progression of diabetic retinopathy. Described insights into pathophysiological mechanisms responsible for DR, could help in the development of more targeted approach for prevention and treatment of diabetic retinopathy. anti

Two-photon excited autofluorescence imaging of freshly isolated frog retinas.

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Lu, Rong-Wen; Li, Yi-Chao; Ye, Tong; Strang, Christianne; Keyser, Kent; Curcio, Christine A; Yao, Xin-Cheng

2011-06-01

The purpose of this study was to investigate cellular sources of autofluorescence signals in freshly isolated frog (Rana pipiens) retinas. Equipped with an ultrafast laser, a laser scanning two-photon excitation fluorescence microscope was employed for sub-cellular resolution examination of both sliced and flat-mounted retinas. Two-photon imaging of retinal slices revealed autofluorescence signals over multiple functional layers, including the photoreceptor layer (PRL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Using flat-mounted retinas, depth-resolved imaging of individual retinal layers further confirmed multiple sources of autofluorescence signals. Cellular structures were clearly observed at the PRL, ONL, INL, and GCL. At the PRL, the autofluorescence was dominantly recorded from the intracellular compartment of the photoreceptors; while mixed intracellular and extracellular autofluorescence signals were observed at the ONL, INL, and GCL. High resolution autofluorescence imaging clearly revealed mosaic organization of rod and cone photoreceptors; and sub-cellular bright autofluorescence spots, which might relate to connecting cilium, was observed in the cone photoreceptors only. Moreover, single-cone and double-cone outer segments could be directly differentiated.

Retinal Imaging Techniques for Diabetic Retinopathy Screening

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Goh, James Kang Hao; Cheung, Carol Y.; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-01-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491

Circulating Reactive Oxidant Causes Apoptosis of Retinal Pigment Epithelium and Cone Photoreceptors in the Mouse Central Retina

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Wei Wang

2011-01-01

Full Text Available Reactive oxidants damage the retinal pigment epithelium (RPE, which is required for viability of overlying photoreceptors. Smoking which leads to chronic accumulation of reactive oxidants in the circulation is linked to age-related macular degeneration (AMD where RPE death is seen along with photoreceptor loss in the central macular region of the retina. It is unclear why this damage is concentrated in the central retina. We asked whether circulating oxidant might specifically target the central retina. Mice were administered the classic reactive oxidant iodate through tail vein injection, and visual acuity was followed by optokinetic response. Histology and apoptosis was examined by H&E and immunostaining. Iodate indeed selectively damaged the central retina, and this damage was highlighted by early apoptosis of RPE in the central retina followed by apoptosis of photoreceptors adjacent to the region of RPE loss–-cones were lost preferentially. The pattern and extent of this damage was independent of exposure to light. We then conclude that circulating oxidant is sufficient to selectively damage the central retina highlighted by sequential apoptosis of RPE and photoreceptors, with cones being the most sensitivity to this RPE loss.

The Dynamics of the Human Infant Gut Microbiome in Development and in Progression Toward Type1 Diabetes

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2016-09-09

SECURITY CLASSIFICATION OF: Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease...susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33...unlimited. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. The views, opinions and/or

Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

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Husain, Shahid; Abdul, Yasir; Crosson, Craig E.

2012-01-01

Morphine, a broad range opioid-receptors agonist, provides retina neuroprotection against glaucomatous injury in chronic experimental rat model. Morphine-induced retina neuroprotection in glaucoma model is mediated partly via inhibition of TNF-alpha production and caspase-3 and caspase-8 activation.

Human beta-cell precursors mature into functional insulin-producing cells in an immunoisolation device: implications for diabetes cell therapies.

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Lee, Seung-Hee; Hao, Ergeng; Savinov, Alexei Y; Geron, Ifat; Strongin, Alex Y; Itkin-Ansari, Pamela

2009-04-15

Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human beta-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human beta-cells and their progenitors and (2) the engraftment of encapsulated murine beta-cells in allo- and autoimmune settings. Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets. Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary beta-cells ameliorated diabetes without stimulating a detectable T-cell response. We demonstrate for the first time that human beta-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of beta-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells.

Human β-cell Precursors Mature Into Functional Insulin-producing Cells in an Immunoisolation Device: Implications for Diabetes Cell Therapies

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Lee, Seung-Hee; Hao, Ergeng; Savinov, Alexei Y.; Geron, Ifat; Strongin, Alex Y.; Itkin-Ansari, Pamela

2009-01-01

Background Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human β-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human β-cells and their progenitors and (2) the engraftment of encapsulated murine β-cells in allo- and autoimmune settings. Methods Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets. Results Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary β-cells ameliorated diabetes without stimulating a detectable T-cell response. Conclusions We demonstrate for the first time that human β-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of β-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells. PMID:19352116

Microvascular disease in children and adolescents with type 1 diabetes and obesity.

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Marcovecchio, M Loredana; Chiarelli, Francesco

2011-03-01

The incidence of type 1 diabetes (T1D) is increasing worldwide and is associated with a significant burden, mainly related to the development of vascular complications. Over the last decades, concomitant with the epidemic of childhood obesity, there has been an increasing number of cases of type 2 diabetes (T2D) among children and adolescents. Microvascular complications of diabetes, which include nephropathy, retinopathy and neuropathy, are characterized by damage to the microvasculature of the kidney, retina and neurons. Although clinically evident microvascular complications are rarely seen among children and adolescents with diabetes, there is clear evidence that their pathogenesis and early signs develop during childhood and accelerate during puberty. Diabetic vascular complications are often asymptomatic during their early stages, and once symptoms develop, there is little to be done to cure them. Therefore, screening needs to be started early during adolescence and, in the case of T2D, already at diagnosis. Identification of risk factors and subclinical signs of complications is essential for the early implementation of preventive and therapeutic strategies, which could change the course of vascular complications and improve the prognosis of children, adolescents and young adults with diabetes.

Fotocoagulação a laser em pacientes portadores de descolamento de retina regmatogênico periférico

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Paulo Escarião

2013-08-01

Full Text Available OBJETIVO: Relatar uma série de casos de descolamento de retina sem envolvimento macular tratados com fotocoagulação a laser. MÉTODOS: Estudo tipo série de casos envolvendo 14 olhos de 12 pacientes com descolamento de retina regmatogênico sem envolvimento macular, retrospectivo, de intervenção. Olhos com procedimentos cirúrgicos prévios foram excluídos. A fotocoagulação a laser foi aplicada com três fileiras confluentes de spot de 300μm, posterior ao descolamento de retina, se extendendo até a ora serrata. A melhor acuidade visual corrigida pré e pós-operatória e a progressão do descolamento de retina foram registrados durante o estudo. RESULTADOS: Treze olhos necessitaram de apenas uma sessão de laser para conter o descolamento de retina. Apenas um olho necessitou de intervenção adicional por causa da evolução do descolamento de retina. Miopia foi encontrada em 7 olhos. Todos os pacientes mantiveram acuidade visual corrigida igual ou melhor que 20/30. CONCLUSÃO:Em casos bem selecionados, a fotocoagulação a laser pode ser considerada para o tratamento de descolamento de retina regmatogênico.

Serum amyloid A is found on ApoB-containing lipoproteins in obese humans with diabetes.

Science.gov (United States)

Jahangiri, Anisa; Wilson, Patricia G; Hou, Tianfei; Brown, Aparna; King, Victoria L; Tannock, Lisa R

2013-05-01

In murine models of obesity/diabetes, there is an increase in plasma serum amyloid A (SAA) levels along with redistribution of SAA from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoprotein particles, namely, low-density lipoprotein and very low-density lipoprotein. The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans. Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n = 14), metabolic syndrome (MetS) obese (n = 8), and obese with type 2 diabetes (n = 6). Plasma was separated into lipoprotein fractions by fast protein liquid chromatography, and SAA was measured in lipid fractions using enzyme-linked immunosorbent assay and Western blotting. Only the obese diabetic group had SAA detectable in apoB-containing lipoproteins, and SAA reverted back to HDL with active weight loss. In human subjects, SAA is found in apoB-containing lipoprotein particles only in obese subjects with type 2 diabetes, but not in healthy obese or obese subjects with MetS. Copyright © 2012 The Obesity Society.

Updates in the Management of Diabetic Macular Edema

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Christopher Mathew

2015-01-01

Full Text Available Diabetes mellitus is a chronic disease which has multiple effects on different end-organs, including the retina. In this paper, we discuss updates on diabetic macular edema (DME and the management options. The underlying pathology of DME is the leakage of exudates from retinal microaneurysms, which trigger subsequent inflammatory reactions. Both clinical and imaging techniques are useful in diagnosing, classifying, and gauging the severity of DME. We performed a comprehensive literature search using the keywords “diabetes,” “macula edema,” “epidemiology,” “pathogenesis,” “optical coherence tomography,” “intravitreal injections,” “systemic treatment,” “hypertension,” “hyperlipidemia,” “anemia,” and “renal disease” and collated a total of 47 relevant articles published in English language. The main modalities of treatment currently in use comprise laser photocoagulation, intravitreal pharmacological and selected systemic pharmacological options. In addition, we mention some novel therapies that show promise in treating DME. We also review systemic factors associated with exacerbation or improvement in DME.

Simulating the Effects of Laser Damage to the Retina

National Research Council Canada - National Science Library

2001-01-01

This Phase II SBIR brought vision and signal processing researchers from the Air Force, academia and the public sector together to develop a visualization tool for modeling laser damage to the retina...

Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

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Meguro, Akira; Ideta, Hidenao; Ota, Masao; Ito, Norihiko; Ideta, Ryuichi; Yonemoto, Junichi; Takeuchi, Masaki; Uemoto, Riyo; Nishide, Tadayuki; Iijima, Yasuhito; Kawagoe, Tatsukata; Okada, Eiichi; Shiota, Tomoko; Hagihara, Yuta; Oka, Akira; Inoko, Hidetoshi; Mizuki, Nobuhisa

2012-01-01

Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6), OR = 0.63 and Pc = 1.0 × 10(-5), OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina.

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Akira Meguro

Full Text Available Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4 gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6, OR = 0.63 and Pc = 1.0 × 10(-5, OR = 0.69 in a total of 574 patients and 608 controls, respectively. Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

Myopathy associated with pigmentary degeneration of the retina and high protein content of cerebrospinal fluid Miopatia associada a degeneração pigmentar da retina e hiperproteinorraquia

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José Antonio Levy

1974-06-01

Full Text Available The cases of two brothers suffering from a myopathy associated with pigmentary degeneration of the retina and increase of protein content of the cerebrospinal fluid are reported.Foram estudados dois pacientes, filhos de pais não consanguíneos, com quadro miopático, iniciado na segunda década da vida, com predomínio na musculatura das cinturas e da face. Em ambos os casos havia degeneração pigmentar da retina e aumento da taxa protéica no líquido cefalorraqueano.

Light regulation of the insulin receptor in the retina.

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Rajala, Raju V S; Anderson, Robert E

2003-10-01

The peptide hormone insulin binds its cognate cell-surface receptors to activate a coordinated biochemical-signaling network and to induce intracellular events. The retina is an integral part of the central nervous system and is known to contain insulin receptors, although their function is unknown. This article, describes recent studies that link the photobleaching of rhodopsin to tyrosine phosphorylation of the insulin receptor and subsequent activation of phosphoinositide 3- kinase (PI3K). We recently found a light-dependent increase in tyrosine phosphorylation of the insulin receptor-beta-subunit (IR beta) and an increase in PI3K enzyme activity in isolated rod outer segments (ROS) and in anti-phosphotyrosine (PY) and anti-IR beta immunoprecipitates of retinal homogenates. The light effect, which was localized to photoreceptor neurons, is independent of insulin secretion. Our results suggest that light induces tyrosine phosphorylation of IR beta in outer-segment membranes, which leads to the binding of p85 through its N-terminal SH2 domain and the generation of PI-3,4,5-P3. We suggest that the physiological role of this process may be to provide neuroprotection of the retina against light damage by activating proteins that protect against stress-induced apoptosis. The studies linking PI3K activation through tyrosine phosphorylation of IR beta now provide physiological relevance for the presence of these receptors in the retina.

A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy

NARCIS (Netherlands)

van Geest, Rob J.; Lesnik-Oberstein, Sarit Y.; Tan, H. Stevie; Mura, Marco; Goldschmeding, Roel; van Noorden, Cornelis J. F.; Klaassen, Ingeborg; Schlingemann, Reinier O.

2012-01-01

Introduction In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF

Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.

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Ari, Seyhmus; Nergiz, Yusuf; Cingü, Abdullah Kürşat; Atay, Ahmet Engin; Sahin, Alparslan; Cinar, Yasin; Caca, Ihsan

2013-03-01

To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.

Edaravone Protect against Retinal Damage in Streptozotocin-Induced Diabetic Mice

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Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

2014-01-01

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes. PMID:24897298

Edaravone protect against retinal damage in streptozotocin-induced diabetic mice.

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Dongqing Yuan

Full Text Available Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p. treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs damage was evaluated by recording the pattern electroretinogram (ERG. RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining, and the levels of reactive oxygen species (ROS were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes.

The Role of Circulating Slit2, the One of the Newly Batokines, in Human Diabetes Mellitus

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Yea Eun Kang

2017-09-01

Full Text Available BackgroundSlit2 is a new secreted protein from adipose tissue that improves glucose hemostasis in mice; however, there is no study about the serum levels and precise role of Slit2 in human. The aim of this study is to explore the serum level of Slit2 in human, and to identify the role of Slit2 in diabetes mellitus (DM.MethodsThe participants of this study consist of 38 subjects with newly diagnosed DM, and 75 healthy subjects as a control group. Serum Slit2 levels were measured using an enzyme-linked immunosorbent assay. Relationship between circulating Slit2 and diabetic related factors was investigated in diabetic group compared with non-diabetic group. Additionally, the correlations between the serum level of Slit2 and diverse metabolic parameters were analyzed.ResultsCirculating Slit2 level was more decreased in diabetic group than in control group, but there was no significant difference statistically. Interestingly, serum levels of Slit2 were significantly negatively correlated to the serum concentrations of fasting glucose (coefficient r=–0.246, P=0.008, the serum concentrations of postprandial glucose (coefficient r=–0.233, P=0.017, and glycosylated hemoglobin (HbA1c; coefficient r=–0.357, P<0.001.ConclusionFrom our study, the first report of circulating Slit2 levels in human, circulating Slit2 level significantly negatively correlated with serum glucose and HbA1c. Our results suggest that the circulating Slit2 may play a role in maintainence of glucose homeostasis in human, even though exact contribution and mechanism are not yet known.

Effects and Responses to Spaceflight in the Mouse Retina

Science.gov (United States)

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

2011-01-01

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

Implications of the new Food and Drug Administration draft guidance on human factors engineering for diabetes device manufacturers.

Science.gov (United States)

Wilcox, Stephen B; Drucker, Daniel

2012-03-01

This article discusses the implications of the new Food and Drug Administration's draft guidance on human factors and usability engineering for the development of diabetes-related devices. Important considerations include the challenge of identifying users, when the user population is so dramatically broad, and the challenge of identifying use environments when the same can be said for use environments. Another important consideration is that diabetes-related devices, unlike many other medical devices, are used constantly as part of the user's lifestyle--adding complexity to the focus on human factors and ease of use emphasized by the draft guidance. © 2012 Diabetes Technology Society.

Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina

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Natsuyo Hata

2008-08-01

Full Text Available Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1, SAPK/ERK kinase 1 (SEK1 and c-Jun N-terminal kinase (JNK is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

Risk factors of diabetic retinopathy in type 2 diabetic patients

Institute of Scientific and Technical Information of China (English)

CAI Xiao-ling; WANG Fang; JI Li-nong

2006-01-01

Background Advances in treatment have greatly reduced the risk of blindness from this disease, but because diabetes is so common, diabetic retinopathy remains an important problem. The purpose of this study is to investigate the risk factors of diabetic retinopathy (DR) in Chinese type 2 diabetic patients.Methods Totally 746 type 2 diabetic patients were selected for biochemical and clinical characteristics test and examined by the retina-camera for diabetic retinopathy and the average age was 55.9 years old.Results A total of 526 patients was classified as non-DR, 159 patients as non-proliferative-DR and 61 patients as proliferative-DR. Duration of diabetes [(66.09±72.51) months vs (143.71 ±93.27) months vs (174.30±81.91)months, P=0.00], systolic blood pressure [(131.95±47.20) mmHg vs (138.71 ±21.36) mmHg vs (147.58±24.10)mmHg, P=0.01], urine albumin [(32.79± 122.29) mg/L vs (190.96±455.65) mg/L vs (362.00±552.51) mg/L,P=0.00], glycated hemoglobin (HbA1c) [(8.68 ± 2.26)% vs (9.42±1.84)% vs (9.42±1.96)%, P=0.04],C-reactive protein (CRP) [(3.19±7.37) mg/L vs (6.36± 23.59) mg/L vs (3.02±4.34) mg/L, P=0.03],high-density lipoprotein cholesterol (HDL-C) [(1.23±0.37) mmol/L vs (1.33±0.35) mmol/L vs (1.24±0.33)mmol/L, P=0.01], uric acid (UA) [(288.51 ±90.85) mmol/L vs (300.29±101.98) mmol/L vs (337.57±115.09)mmol/L, P=0.00], creatinine (CREA) [(84.22±16.31) μmol/L vs (89.35±27.45) μmol/L vs (103.28±48.64)μmol/L, P=0.00], blood urine nitrogen (BUN) [(5.62± 1.62) mmol/L vs (6.55±2.74) mmol/L vs (8.11±3.60)mmol/L, P=0.00] were statistically different among the three groups. Logistic regression analysis showed that diabetic duration and urine albumin were two independent risk factors of DR (the OR values were 1.010 and 1.003 respectively).Conclusions Diabetic duration and urine albumin are two independent risk factors of diabetic retinopathy in elderly type 2 diabetic patients.

Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain

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Jean-François Bouchard

2016-01-01

Full Text Available Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G-protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Müller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases.

[Lattice degeneration of the retina].

Science.gov (United States)

Boĭko, E V; Suetov, A A; Mal'tsev, D S

2014-01-01

Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.

[Transcranial magnetotherapy for the correction of initial manifestations of diabetic retinopathy in children].

Science.gov (United States)

Nikolaeva, N V; Bolotova, N V; Kamenskikh, T G; Raĭgorodskiĭ, Iu M; Kolbenev, I O; Luk'ianov, V F

2009-01-01

This study included 45 children at the age from 5 to 17 years with type I diabetes mellitus complicated by diabetic retinopathy. All the patients showed retinal thickening at the macula and reduced amplitude of local electroretinogram suggesting compromised capillary circulation. The capillary blood flow was corrected by transcranial magnetotherapy with the use of an AMO-ATOS Ogolovie unit. The results of the treatment were evaluated from characteristics of laser Doppler flometry. A course of transcranial magnetotherapy comprising 10 daily seances resulted in a significant increase of microcirculation index, respiratory rhythm, and myogenic tone (by 1.64, 1.35, and 1.16 times respectively). In addition, morphometric and electrophysiological properties of the retina underwent positive changes. Transcranial exposure to the traveling magnetic field is recommended for the correction of intraocular microcirculation and prevention of diabetic macular oedema.

Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

Directory of Open Access Journals (Sweden)

Virginia M Barnes