Oxygen-induced retinopathy in the rat: relationship of retinal nonperfusion to subsequent neovascularization

Abstract

Purpose: To confirm a relationship between oxygen-induced retinal vasoattenuation 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 varying between 40% and 80% in a cyclic fashion. The frequency of the change in inspired oxygen (FiO2) was either 6, 12, 24, or 48 hours. The exposures periods lasted for 14 days, at which time some rats from each exposure group were sacrificed and assessed for retinal vasoattenuation with injection of fluorescein-labeled dextran. The remaining rats from 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 ADPase activity.

Results: Of all rats raised in variable oxygen, 62% exhibited abnormal retinal neovascularization after 4 days in room air. Only 18% of the rats exposed to constant oxygen responded with abnormal neovascularization. Among the four groups of variable oxygen-exposed rats, there was a direct correlation (R2 = 0.96) between degree of retinal avascularity upon removal from oxygen and the propensity for subsequent abnormal neovascularization. Constant oxygen-exposed rats did not exhibit this relationship. This exposure produced the greatest retinal 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 neovascularization in oxygen-induced retinopathy. Other hypotheses bear consideration, including the possibility that variable oxygen leads directly to vascular endothelial cell mitosis, a common retinal manifestation of ischemia-reperfusion.