The Effects Of Intravitreous Mycobacterium Bovis BCG On Retinal Neovascularization In Rabbits

Abstract

Purpose: : To evaluate a novel model of intraocular neovascularization caused by mycobacterial antigen-induced inflammatory response.

Methods: : Thirty New Zealand rabbits were divided into six groups (n=5). All groups received intravitreous injections of 5x10^6 dead Mycobacterium bovis BCG; BSS was used as control. Animals were sacrificed at days 7, 15, 30, 45, and 60. At these time points, clinical evaluations were performed using color fundus photographs and fluorescein angiography (FA). Enucleated eyes were processed for hematoxylin and eosin staining. VEGF and 8-OHdG were measured by qRT-PCR and immunohistochemistry respectively.

Results: : At days 7 and 15 post inoculation of mycobacterium bovis BCG, the histopathology study showed inflammatory infiltration at the retina level with inflammatory leakage into the vitreous cavity (blood retinal barrier breakdown). Clinical data showed disc hyperemia, retinal vascular dilatation and tortuosity. FA showed disc leakage and presence of retinal neovascular membranes (NVM). At days 30, 45 and 60, the NVM were replaced by a fibrotic membrane and caseum type material. To quantify this leakage, VEGF was measured. Blood retinal barrier breakdown corresponded to a sustained release of VEGF. In addition, RPE cells showed a significant increased in positive 8-OhdG cells after injection of M. bovis BCG in all groups. Control eyes, remained unchanged and normal during the entire course of this study.

Conclusions: : This is the first model of mycobacterial antigens-induced neovascularization in rabbits in which the pathological events following overexpression of VEGF and oxidative stress by RPE cells have been described. Intravitreous injection of mycobacterium bovis BCG in rabbits results in retinal neovascularization by day fifteen.

Keywords: inflammation • neovascularization • retina