Radiobiological Study of Retinal Microvessel Proliferation in Diabetic-like Rat Model

Abstract

Progressive evolution of retinal vascular in diabetic retinopathy leads to blindness in up to 8,000 patients yearly. The major purpose of this investigation was to determine proton radiation dose response of the eye's retinal vascu- lature in the hypergalactosemia induced rat model of diabetic-like retinopathy and gain insight of possible role of proton radiotherapy in controlling diabetic retinopathy. A single dose range of proton radiation (8, 14, and 20 Gy) was delivered to one eye of each rat at 4 months following induction of hypergalactosemia. The opposite eye of each rat, which was not irradiated, showed normal progression of retinopathy. Stereologic techniques were used to quantify tissue parameters in situ in a retinal digest preparation that allowed unobstructed access to the vasculature. 15 months following 50% galactose diet, characteristic histopathological lesions of retinopathy such as capillary endothelial cell proliferation, capillary clo- sure, capillary microaneurysms, pericyte loss developed in non-irradiated eyes. The endothelial cell densities for rat re- ceiving 50% galactose diet were significantly higher than that of control (p<0.05). Proton irradiation inhibited significant endothelial cell proliferation at dose from 14Gy to 20Gy (p<0.05), yet not diminished pericyte loss at current dose sched- ule. These findings indicated beneficial effects of proton radiation on hypergalactosemia induced diabetic-like retinopa- thy. Our study should have an impact on further studies to optimize radiation treatment strategies for diabetic retinopathy.