Structural and functional consequences of trolox C treatment in the rat model of postnatal hyperoxia.

ABSTRACT

PURPOSE: Previous studies have shown that newborn rats exposed to hyperoxia within the first 2 weeks of life develop vasculopathy in addition to permanent changes in retinal structure and function. It has also been suggested that free radicals may be the source of these pathologic effects. Trolox C, a water-soluble analogue of vitamin E, was previously shown to limit the vascular consequences of exposure to postnatal hyperoxia. The aim of this study was to investigate whether trolox C could also help prevent the functional (electroretinography) and structural (retinal histology) consequences associated with oxygen-induced retinopathy (OIR). METHODS: Newborn albino Sprague-Dawley rats exposed or not exposed to hyperoxia received daily injections of trolox C in doses of 300, 600, and 900 microg/kg (total volume, 50 microL). The effect of treatment was evaluated through electroretinography and retinal histology. RESULTS: Although trolox C tended to have a retinoactive effect on the normal retina, normalization of the hyperoxia-treated group to hyperoxic control and of the normoxia-treated group to normoxic control revealed that the a-wave remained relatively unaffected by hyperoxia exposure and by treatment with trolox C, the efficacy of trolox C at doses of 600 and 900 microg/kg largely outweighed the retinoactive effect, and the oscillatory potentials (OPs) benefited to the greatest extent from trolox C treatment. Furthermore, trolox C was able to limit the reduction in outer plexiform layer thickness but not the concomitant reduction of the horizontal cell count, each of which is associated with OIR. CONCLUSIONS: These results show that, as had been previously demonstrated with retinal vasculature, trolox C limited the retinal functional and structural damages inherent in the rat model of OIR. However, despite treatment, there were still signs (albeit less severe) indicative of OIR. This suggests, as previously advanced, that the pathophysiology of OIR is not solely caused by the action of free radicals or that trolox C is inadequate in treating all aspects of OIR.