NDLI: Retinal gene expression and visually evoked behavior in diabetic long evans rats.

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Retinal gene expression and visually evoked behavior in diabetic long evans rats.

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Retinal gene expression and visually evoked behavior in diabetic long evans rats.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kirwin, Stefanie J. Edelman, Jeffrey L. Cairns, Belinda J. Kanaly, Suzanne T. Hansen, Candice R. Ren, Meina
Description	Country affiliation: United States Author Affiliation: Kirwin SJ ( Department of Biological Sciences, Allergan, Inc., Irvine, California 92612, USA. kirwin_stefanie@allergan.com)
Abstract	PURPOSE: Patients with diabetic retinopathy may experience severe vision loss due to macular edema and neovascularization secondary to vascular abnormalities. However, before these abnormalities become apparent, there are functional deficits in contrast sensitivity, color perception, and dark adaptation. The goals of this study are to evaluate early changes (up to 3 months) in retinal gene expression, selected visual cycle proteins, and optokinetic tracking (OKT) in streptozotocin (STZ)-induced diabetic rats. METHODS: Retinal gene expression in diabetic Long Evans rats was measured by whole genome microarray 7 days, 4 weeks, and 3 months after the onset of hyperglycemia. Select gene and protein changes were probed by polymerase chain reaction (PCR) and immunohistochemistry, respectively, and OKT thresholds were measured using a virtual optokinetics system. RESULTS: Microarray analysis showed that the most consistently affected molecular and cellular functions were cell-to-cell signaling and interaction, cell death, cellular growth and proliferation, molecular transport, and cellular movement. Further analysis revealed reduced expression of several genes encoding visual cycle proteins including lecithin/retinol acyltransferase (LRAT), retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65), and RPE retinal G protein-coupled receptor (RGR). These molecular changes occurred simultaneously with a decrease in OKT thresholds by 4 weeks of diabetes. Immunohistochemistry revealed a decrease in RPE65 in the RPE layer of diabetic rats after 3 months of hyperglycemia. CONCLUSIONS: The data presented here are further evidence that inner retinal cells are affected by hyperglycemia simultaneously with blood retinal barrier breakdown, suggesting that glial and neuronal dysfunction may underlie some of the early visual deficits in persons with diabetes.
ISSN	01460404
e-ISSN	15525783
Journal	Investigative Opthalmology & Visual Science
Issue Number	10
Volume Number	52
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2011-09-29
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Diabetes Mellitus, Experimental Genetics Diabetic Retinopathy Evoked Potentials, Visual Physiology Eye Proteins Gene Expression Regulation Retinal Pigment Epithelium Metabolism Animals Blood-retinal Barrier Carrier Proteins Physiopathology Gene Expression Profiling Immunohistochemistry Nystagmus, Optokinetic Oligonucleotide Array Sequence Analysis Rats, Long-evans Real-time Polymerase Chain Reaction Receptors, G-protein-coupled Cis-trans-isomerases Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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