Intraocular Pressure-Induced Endothelial Dysfunction of Retinal Blood Vessels Is Persistent, but Does Not Trigger Retinal Ganglion Cell Loss.

Abstract

Research has been conducted into vascular abnormalities in the pathogenesis of glaucoma, but conclusions remain controversial. Our aim was to test the hypothesis that retinal endothelial dysfunction induced by elevated intraocular pressure (IOP) persists after IOP normalization, further triggering retinal ganglion cell (RGC) loss. High intraocular pressure (HP) was induced in mice by episcleral vein occlusion (EVO). Retinal vascular function was measured via video microscopy in vitro. The IOP, RGC and their axons survival, levels of oxidative stress and inflammation as well as vascular pericytes coverage, were determined. EVO caused HP for two weeks, which returned to baseline afterwards. Mice with HP exhibited endothelial dysfunction in retinal arterioles, reduced density of RGC and their axons, and loss of pericytes in retinal arterioles. Notably, these values were similar to those of mice with recovered IOP (RP). Levels of oxidative stress and inflammation were increased in HP mice but went back to normal in the RP mice. Our data demonstrate that HP induces persistent endothelial dysfunction in retinal arterioles, which persists one month after RP. Oxidative stress, inflammation, and loss of pericytes appear to be involved in triggering vascular functional deficits. Our data also suggest that retinal endothelial dysfunction does not affect RGC and their axon survival.