Retrolental fibroplasia: evidence for a role of the prostaglandin cascade in the pathogenesis of oxygen-induced retinopathy in the newborn beagle

Abstract

Aspirin administration, at a dosage producing plasma levels within the human therapeutic range, caused marked inhibition of production of both vascular prostacyclin (a vasodilator) and platelet thromboxane (a vasoconstrictor) in beagle puppies. In addition, aspirin-treated, oxygen-exposed puppies developed retinopathy of significantly greater severity than their unmedicated, oxygen-exposed littermates. Direct ophthalmoscopic observations indicated that whereas sustained oxygen breathing produced retinal vasoconstriction in unmedicated puppies, retinal vessels of aspirin-treated littermates became more dilated or remained unchanged. It is postulated that retinal vasoconstriction may be a normal physiologic mechanism to protect the immature retina from damaging effects of high blood oxygen levels; i.e., it may be a protective rather than a pathologic process in response to hyperoxia. Many vascular anomalies which characterize the human disease were present in the retinas of the puppies. Several of the most severely affected puppies treated with aspirin even displayed grade III cicatricial retinopathy (falciform retinal fold). Thus, a major criticism of the retrolental fibroplasia animal model has been addressed by producing cicatricial retrolental fibroplasia in puppies, and the confidence with which results from experimental animal studies might be extrapolated to the clinical situation is thereby strengthened.