Evidence Suggesting that Postnatal Hyperoxia Induces a Progressive Retinal Degeneration in Long Evans Rats

Abstract

Abstract: : Purpose: Last year we showed that pigmented Long Evans (LE) rats reacted more strongly than albino Sprague Dawley (SD) rats to postnatal hyperoxia suggesting that the melanin pigment might not have the protective (antioxidant) effect previously suggested. The purpose of this study was to further investigate this discrepancy. Methods: Newborn LE rats were exposed to hyperoxia as previously described (ARVO 2002). Scotopic (intensity:-6.3 to 0.6 log cd.m^-2.sec; 12 hrs dark adaptation) and photopic (intensity:0.9 log cd.m^-2.sec; background: 30cd.m^-2) ERGs were recorded at postnatal days 30 and 60. Retinal sections (enucleation at 60 days, 0.7µm sections, toluidine blue staining) were also analyzed. Results: Measurements obtained at 30 days of age indicate that hyperoxia during the first week of life (0-6) did not significantly modify the scotopic ERG a-wave compared to 30% reduction during the second week of life (6-14, 9-14) and 50% for exposure which included the first two weeks of life (0-14). A further 20% (6-14, 9-14) and 15% (0-14) decrease was observed in 60 day measurements. In contrast, the photopic b-wave, which was reduced by 65% compared to control after exposure from 0-6 and by 85% after exposure from 0-14 at 30 days, showed a slight amplitude recovery (8% gain) at 60 days. Histological analysis at 60 days revealed a thinning of the OPL (normal: 15.75 ±0.10µm; 0-14: 2.8±1.46µm; p<.05 ); INL (normal:32.5±0.52µm; 0-14: 20.325±0.84µm; p<.05, reduced from 4.71±.58µm cells thick (normal) to 2.8±1.2µm (0-14); p<.05); IPL thickness (normal: 53.2±0.78µm; 0-14: 33.13±1.5µm; p<.05 ). Conclusions: In a previous study we showed that OIR in SD rats did not evolve with time. The structural and functional anomalies observed at 30 days remained the same at 60 days. In contrast, the OIR in LE rats is much more severe and shows signs of deterioration (as per ERG) over time. Furthermore, while the structural anomaly in SD rats is limited to the OPL, it is more extensive in LE rats. One wonders if the more severe oxygen induced retinopathy observed in LE rats might result from melanin exerting its' pro-oxidant effect upon exposure of these rats to hyperoxic conditions, thus exacerbating the effect of O₂ radicals in the retina and lead to a degenerative path (compared to a destructive path in SD rats). Funded by: CIHR and Réseau Vision

Keywords: electroretinography: non-clinical • retina • oxidation/oxidative or free radical damage