Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure
| Autor: | Zsolt Ablonczy, Mohammad Dahrouj, Yueying Liu, Craig E. Crosson, Danielle Desjardins |
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| Rok vydání: | 2015 |
| Předmět: |
Glycation End Products
Advanced Vascular Endothelial Growth Factor A medicine.medical_specialty Immunoblotting Retinal Pigment Epithelium Macular Edema Article RAGE (receptor) Pathogenesis Cellular and Molecular Neuroscience Glycation Internal medicine Blood-Retinal Barrier Cadaver Animals Humans Medicine Glycated Serum Albumin Receptor Cells Cultured Serum Albumin Retinal pigment epithelium business.industry Antagonist Kinase insert domain receptor Immunohistochemistry Vascular Endothelial Growth Factor Receptor-2 eye diseases Sensory Systems Resorption Disease Models Animal Ophthalmology Endocrinology medicine.anatomical_structure Rabbits sense organs business Tomography Optical Coherence |
| Zdroj: | Experimental Eye Research. 137:50-56 |
| ISSN: | 0014-4835 |
| Popis: | Diabetic macular edema (DME) is a major cause of visual impairment. Although DME is generally believed to be a microvascular disease, dysfunction of the retinal pigment epithelium (RPE) can also contribute to its development. Advanced glycation end-products (AGE) are thought to be one of the key factors involved in the pathogenesis of diabetes in the eye, and we have previously demonstrated a rapid breakdown of RPE function following glycated-albumin (Glyc-alb, a common AGE mimetic) administration in monolayer cultures of fetal human RPE cells. Here we present new evidence that this response is attributed to apically oriented AGE receptors (RAGE). Moreover, time-lapse optical coherence tomography in Dutch-belted rabbits 48 h post intravitreal Glyc-alb injections demonstrated a significant decrease in RPE-mediated fluid resorption in vivo. In both the animal and tissue culture models, the response to Glyc-alb was blocked by the relatively selective RAGE antagonist, FPS-ZM1 and was also inhibited by ZM323881, a relatively selective vascular endothelial growth factor receptor 2 (VEGF-R2) antagonist. Our data establish that the Glyc-alb-induced breakdown of RPE function is mediated via specific RAGE and VEGF-R2 signaling both in vitro and in vivo. These results are consistent with the notion that the RPE is a key player in the pathogenesis of DME. |
| Databáze: | OpenAIRE |
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