Retrolental Fibroplasia: Evidence for a Role of the Prostaglandin Cascade in the Pathogenesis of Oxygen-Induced Retinopathy in the Newborn Beagle

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Abstract
Summary: Aspirin administration, at a dosage producing plasma levels within the human therepeutic 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 aspirintreated 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. Speculation: It is conceivable that the susceptibility of any eye to oxygen-associated retinopathy at birth depends upon the extent to which the vasoconstriction protective response is functional as well as upon the degree of retinal vascular maturity attained. In utero, the arterial PO2 is low, and blood flow to the immature retina is high. When the PO2 rises at birth, retinal blood flow does not change, although arterial blood pressure rises; this could be explained by the occurrence of some degree of vasoconstriction in response to elevated arterial PO2 or reduced PO2 which establishes the clinically normal retinal vasotonia. In light of this, those cases of “spontaneous” retrolental fibroplasia reported in premature infants never administered oxygen or in full-term infants who were administered oxygen might simply be examples of individuals with inadequate retinal vasotonia for protection of structurally immature vessels from the effects of elevated arterial PO2, and/or excessively high transmural pressure.