Retinal neovascularization is prevented by blockade of the renin-angiotensin system

Both angiotensin II and vascular endothelial growth factor are angiogenic a gents that have recently been implicated in the pathogenesis of proliferati ve diabetic retinopathy. In this study, retinal neovascularization was exam ined in a model of retinopathy of prematurity with the use of neonatal tran sgenic (mRen-2)27 rats, which overexpress renin in tissues, and Sprague-Daw ley rats. Blockers of the renin-angiotensin system were administered during the neovascularization period, The ACE inhibitor lisinopril and the angiot ensin type 1 receptor antagonist losartan both increased retinal renin leve ls and prevented inner retinal blood vessel growth. Quantitative in situ hy bridization revealed that the expression of vascular endothelial growth fac tor and its type 2 receptor in the inner retina and proliferating blood ves sels were increased in rats with retinopathy of prematurity, Lisinopril red uced both retinal vascular endothelial growth factor and its type 2 recepto r mRNA in retinopathy of prematurity rats, whereas losartan had no effect, It is predicted that agents that interrupt the renin-angiotensin system may play an important role as retinoprotective agents in various forms of prol iferative retinopathy.