Abstract
Purpose: :
Previous studies have shown that neonatal rats exposed to hyperoxia from P0-14 develop a vasculopathy in addition to permanent changes in retinal structure and function. The purpose of this study was to determine whether the neuroprotectant free radical scavenging effect of 17-ß-estradiol could help prevent the functional (electroretinography) consequences associated with oxygen-induced retinopathy (OIR).
Methods: :
Newborn albino Sprague-Dawley (SD) rats exposed to hyperoxia [80% O2 for 22.5 hours from P0-14] or raised in room air received daily injections of 17-ß-estradiol from P5-14 in doses of 100 and 200µg/kg (80% O2:n=5 and 4, respectively; 21% O2:n=5 and 5, respectively) and were compared to non-injected normoxic and hyperoxic controls. Scotopic (intensity: -6.3 to 0.6 log cd.sec.m-2; 12 hours dark adaptation) and photopic (intensity: 0.9 log cd.sec.m-2; background: 30 cd.m-2)] electroretinograms (ERG) were recorded at P30
Results: :
Although 17-ß-estradiol tended to have a retinoactive effect on normoxic cohorts irrespective of dose (18% increase in amplitude for all ERG parameters compared to non-injected controls), its effect in hyperoxic cohorts markedly outweighed the latter in a dose-dependant manner (a-wave: 44% and 61% and mixed rod-cone b-wave: 53% and 69.4% increase in amplitude following 100 and 200µg/kg injections, respectively, compared to control, p<0.05). In contrast, neither concentration significantly improved the photopic b-wave, which remained attenuated to 20% of control.
Conclusions: :
Our findings suggest that 17-ß-estradiol injections can significantly prevent the loss of retinal function in a dose dependant manner, though it’s therapeutic effect could not entirely eradicate all features of OIR, namely the significantly attenuated photopic b-wave which we have previously shown to be the most susceptible ERG parameter in this model. This could suggest, as previously described, that while free radicals might play a role in the pathogenesis of OIR, they are not solely responsible. One wonders whether the decreased susceptibility of neonatal rats to early oxygen exposure (P0-6), as previously described by us, could result from increased serum levels of estrogen that remain high immediately following the fetal period, and whether maintaining these levels as such result in the observed protective effect. Funded by Réseau Vision and CIHR.
Keywords: retina • electroretinography: non-clinical • retinopathy of prematurity