Angiopoietin-2-related modulation of retinal angiogenesis – A new model for diabetic retinopathy

Abstract

Diabetic retinopathy is the most prevalent cause of blindness among adults of working age. The earlies discernible lesion in the diabetic retina is pericyte loss. The Angiopoietin-Tie system plays a central role in this process. We examined the impact of retinal Angiopoietin 2 (Ang-2) overexpression on capillary cell cross-talk. We established and characterized a transgenic mouse which expresses human Ang-2 under control of a murin opsin promoter. Physiological sprouting of postnatal retinal vessels was examined in lectin-stained retinal whole mount preparations. Quantitative morphometry of retinal digest preparations was used to assess the endothelial/pericyte ratio as a measure of changes in the cellular composition of capillaries. The effect of retinal Ang-2 overexpression on pathological neovascularization was studied in the mouse model of hypoxia-induced proliferative retinopathy. Physiological sprouting was accelerated by Ang-2 overexpression, in association with a 17% deficit of pericytes in the deep capillary layers. MOpsinHAng-2 mice had significantly more retinal neovascularizations, both within and outside the retina, compared with controls. Taken together, our data suggest that Ang-2 is involved in the interaction between pericytes and endothelial cells, and may play an important role in the response-to-injury of the diabetic vessel system.