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I. Klaassen, J.M. Hughes, R.O. Schlingemann; The Effects of Vascular Endothelial Growth Factor on Rat Retinal Gene Expression . Invest. Ophthalmol. Vis. Sci. 2004;45(13):682.
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Purpose: Increased permeability of retinal blood vessels is an important cause of loss of vision in patients with diabetic retinopathy (DR). Vascular endothelial growth factor–A (VEGF) is found to be involved in this leakage, possibly by inducing active changes in transendothelial transport via caveolae (pinocytotic vesicles). Methods: In order to explore cellular mechanisms underlying microvascular leakage in DR, recombinant human VEGF165 (rhVEGF165) or PBS was injected intra–vitreally in male Wistar rats (n=8). Gene expression after 24h was investigated in retinas by real–time quantitative RT–PCR and oligo microarray analysis. Results: Q–PCR results demonstrated an increased expression of known VEGF–inducible genes in the VEGF–injected eye as compared to the control eye, such as angiopoietin–2, alpha–2–macroglobulin, Collagen IV, Fibronectin, ICAM–1, VCAM–1, E–selectin and PECAM–1. Microarray analysis showed an increased expression of VEGF–related genes, genes involved in diabetes–related biochemical pathways and a number of unknown genes. Interestingly, one unknown highly differentially expressed gene was identified as Syndapin Iiaa. This is a member of the PACSINs, a family of cytoplasmic phosphoproteins that play a role in vesicle formation and transport. Conclusions: VEGF–injection in rat eyes as compared to controls caused differential regulated gene expression of genes that are VEGF– and diabetes–related. Differential expression of a novel gene involved in vesicle formation, suggests the activation of transendothelial transport via vesicles, a possible mechanism of vascular leakage in DR.
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