Role of vascular endothelial growth factor-165b in the breakdown of the blood-retinal barrier after acute high intraocular pressure in rats

Abstract

Background: The blood-retinal barrier (BRB) is essential in maintaining the retinal homeostasis of the microenvironment, previous studies have found that BRB breakdown occurs after acute high intraocular pressure (HIOP) in rats, elevated intraocular pressure can induce upregulation of vascular endothelial growth factor-165b (VEGF-165b) protein in the retina, but the role of VEGF-A165b in BRB breakdown after acute HIOP is still undetermined. Methods: In this study, the rat acute HIOP model was established before and after intravitreous injection of anti-VEGF-165b antibody. The expression of VEGF-165b and ZO-1 in rat retina was detected by immunohistochemistry or western blotting, and the breakdown of BRB was detected by Evans blue (EB) dye. Results: The normal retina of rats expressed VEGF-165b protein, which was mainly located in the retinal ganglion cell (RGC) layer and the inner nuclear layer and was coexpressed with tight junction protein ZO-1. After acute HIOP, the expression of VEGF-165b was upregulated (P < 0.01); The expression of ZO-1 was downregulated (P < 0.01) at 12 h and then recovered at 3 d; EB leakage increased, peaking at 12 h (P < 0.01). After intravitreous injection of anti-VEGF-165b antibody, the expression of VEGF-165b protein was significantly downregulated (P < 0.01); and the downregulation of the expression of ZO-1 was more obvious (P < 0.01); EB leakage became more serious, peaking at 3 d (P < 0.01). EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina (P < 0.01). Conclusions: The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1. The differential destruction of BRB after acute HIOP may be related to the selective loss of RGCs.