Preclinical Model for Proliferative Diabetic Retinopathy (PDR)

Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with untreated PDR, we found elevated levels of a gene called hypoxia inducible factor 1 alpha (HIF1α). We created a model of human diabetic retinopathy in a mouse by knocking out a protein called the von Hippel Lindau tumor suppressor protein in the neural retina. This protein breaks down HIF1α in the human body, and therefore our mouse model had increased HIF1α in the eye. These mice developed a severe, irreversible ischemic retinopathy that has features of human PDR. The rapid disease progression in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders.