Role of VEGF-A in Endothelial Phenotypic Shift in Human Diabetic Retinopathy and VEGF-A-Induced Retinopathy in Monkeys

Abstract

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 characteristically express PAL-E. Here we investigated the relation between the expression of the PAL-E antigen and vascular endothelial growth factor-A (VEGF) in human post-mortem eyes of individuals with diabetes mellitus (DM) and in experimental VEGF-induced retinopathy in cynomolgus monkeys. Cryosections were cut of eyes of 41 individuals with and 30 individuals without DM and eyes of 2 cynomolgus monkeys who received 4 injections of 0.5 µg VEGF in the vitreous of one eye and PBS in the other. The sections were stained with antibodies against VEGF, PAL-E and endogenous markers for microvascular leakage. Specific retinal vascular staining for VEGF was only observed in 10 out of the 41 cases with DM. These 10 cases also had marked uniform PAL-E staining and widespread vascular leakage. In contrast, diabetic patients without microvascular leakage and controls were negative for VEGF and PAL-E. Likewise, PAL-E was found only in the leaky retinal vessels of monkey eyes injected with VEGF. These results indicate that increased expression of the PAL-E antigen in retinal endothelium in conditions with microvascular leakage is related to VEGF and suggest that VEGF directly or indirectly induces PAL-E. PAL-E expression may reflect important endothelial changes involved in the disturbance of the blood-retina barrier in DR.

A Role for Vascular Deficiency in Retinal Pathology in a Mouse Model of Ataxia-Telangiectasia

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Dietary Taurine Supplementation Prevents Glial Alterations in Retina of Diabetic Rats

“…It has been reported that changes in Müller cells' function often occurred prior to vascular abnormalities [6][7][8]. These changes include the abnormalities in the a and b waves of electroretinogram (ERG) [9][10][11], altered expression of glial fibrillary acidic protein (GFAP) [12][13][14] and vascular endothelial growth factor (VEGF) [15][16][17][18] in the Müller cells, and always combined with alteration in glutamate metabolism [19,20].…”

Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

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