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The role of RPE in the regulation of VEGF
Author(s) -
KLETTNER A
Publication year - 2011
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2011.2233.x
Subject(s) - retina , retinal pigment epithelium , vascular endothelial growth factor , macular degeneration , secretion , choroid , microbiology and biotechnology , retinal , biology , angiogenesis , medicine , endocrinology , ophthalmology , cancer research , neuroscience , vegf receptors
Vascular endothelial growth factor (VEGF) has emerged as a major player in retinal diseases and is strongly involved in choroidal neovascularisation in exudative age‐related macular degeneration (AMD) or in the development of macular edema in diabetic retinopathy. An important source of VEGF in the retina is the Retinal Pigment Epithelium (RPE). The RPE is a highly polarized cell layer situated between the choroid and the photoreceptors and among its many functions is the secretion of cytokines. RPE‐derived VEGF is important for the development of the vasculature of the retina in the premature eye. In the adult eye, the RPE constitutively secrets low amounts of VEGF, mainly on the basolateral side, in order to maintain the choroid and protect endothelial cells. Also, neuroprotective properties of (apical) VEGF have been described. Main isoforms of RPE‐secreted VEGF are VEGF165 and, to a lesser extent, VEGF121. Also, minor amounts of VEGF189 are can be found. VEGF165b, an anti‐angiogenic isoform, might also be secreted by the RPE. Under different noxious stimulations, RPE cells increase their VEGF secretion, via several, stimulus specific, pathways. Among these stimuli, hypoxia, oxidative stress, hyperglycemia, several cytokines and endoplasmic reticulum stress might be closely connected to the pathogenesis of exudative AMD and other neovascular alterations of the retina. Loss of polarity might also contribute to inappropriate VEGF secretion and subsequent neovascular changes. The dichotomy of protective physiological and vision‐threatening pathological VEGF secretion renders the differences of physiological and pathological VEGF expression regulation a highly interesting target for the development of long‐term VEGF inhibiting drugs.