OXYGEN-INDUCED RETINOPATHY IN THE RAT - RELATIONSHIP OF RETINAL NONPERFUSION TO SUBSEQUENT NEOVASCULARIZATION

Purpose. To confirm a relationship between oxygen-induced retinal vaso attenuation and subsequent abnormal neovascularization in the newborn rat. Methods. Beginning at birth, some litters of Sprague-Dawley rats were exposed to 80% constant oxygen while others received oxygen varyi ng between 40% and 80% in a cyclic fashion. The frequency of the chang e in inspired oxygen (FiO(2)) was either 6, 12, 24, or 48 hours. The e xposure periods lasted for 14 days, at which time some rats from each exposure group were sacrificed and assessed for retinal vasoattenuatio n with injection of fluorescein-labeled dextran. The remaining rats fr om each group were transferred at day 14 from the hyperoxic atmosphere to room air for an additional 4 days. These animals were then killed and assessed for retinal neovascularization by staining for vascular A DPase activity. Results. Of all rats raised in variable oxygen, 62% ex hibited abnormal retinal neovascularization after 4 days in room air. Only 18% of the rats exposed to constant oxygen responded with abnorma l neovascularization. Among the four groups of variable oxygen-exposed rats, there was a direct correlation (R(2) = 0.96) between degree of retinal avascularity upon removal from oxygen and the propensity for s ubsequent abnormal neovascularization. Constant oxygen-exposed rats di d not exhibit this relationship. This exposure produced the greatest r etinal avascularity upon removal from oxygen but the lowest incidence of abnormal neovascularization after 4 days in room air. Conclusions. Retinal avascularity may not be the single overriding stimulus for neo vascularization in oxygen-induced retinopathy. Other hypotheses bear c onsideration, including the possibility that variable oxygen leads dir ectly to vascular endothelial cell mitosis, a common retinal manifesta tion of ischemia-reperfusion.