Retinopathy of prematurity (ROP) is a disorder affecting an estimated 5000-6000 premature infants annually in the United States leaving approximately 2000 of them with some visual impairment, and 600 blind. There is little understanding as to why regression or healing of the retinopathy occurs in most of the affected infants while in the others it progresses to vision loss. The goal of this research is to test systemic oxygenation and perfusion factors that clinical surveys reveal as significantly correlated with severe ROP. These factors may control the regression process, and their study lead to clinically applicable therapy. The oxygen induced retinopathy kitten model will be used. Low flow oxygen therapy (28%) following an oxygen induced injury (80% oxygen) in 3 day old kittens will be tested first as a potential therapeutic maneuver suggested by a previous kitten study of variable oxygenation following injury. Second, Chronic hypoxia alone as an inducer of retinopathy will be tested since hypoxia following a high oxygen injury does result in a worse retinopathy. Because human infants with severe recurrent apneic spells and infants how have experienced perinatal asphyxia and/or shock are at increased risk for severe ROP, these physiologic conditions will be the 3rd and 4th hypotheses tested in the kitten to learn if they will reproducibly affect the oxygen induced retinopathy. Oxygen, administered in excess, has dominated the beliefs and attention of physicians as the etiology of ROP for too long, blinding investigators to other possible factors at work. One phase of the proposed research hopes to establish (or discredit) hypoperfusion as an initial insult causing retinopathy in the animal model. Of equal importance, the other phases of the reserach should firmly establish the role of hypoxia during the recovery process of this retinopathy leading to the organization of appropriate clinical trials.
