Incidence and Severity of Neovascularization in Oxygen- and Acidosis-Induced Retinopathy Depends on Rat Source

Abstract

Abstract: : Purpose: We have previously described oxygen-induced retinopathy (OIR) and acidosis-induced retinopathy (AIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP). Given that rats of identical strain from two commercial suppliers are phenotypically different, we investigated the incidence and severity of preretinal neovascularization (NV) in rats from different suppliers using the OIR and AIR models. Methods: Using our established models for OIR and AIR, 400 newborn Sprague-Dawley rats, obtained from Harlan (HSD) and Charles River Laboratories (CR), were raised in 16 expanded litters of 25 (6 OIR and 10 AIR). Beginning at day 1 of life, OIR litters (3 HSD, 3 CR) were exposed to 7 daily cycles of hyperoxia (80% O₂, 20.5 hours) and hypoxia (10% O₂, 0.5 hours) with a gradual return to 80% O₂ over 3 hours. OIR rats were sacrificed after 5 days of room air recovery. AIR litters (5 HSD, 5 CR) were raised in room air and gavaged twice daily with NH₄Cl (10mM/kg body weight) from day 2 to day 4 of life. AIR rats were sacrificed after 3 days of recovery. For both OIR and AIR litters, retinae from left eyes were dissected, ADPase-stained, and flat-mounted. Presence and severity of NV was scored and retinal vascular areas measured by a masked observer. Results: In OIR rats, the incidence of NV was higher in CR rats than HSD rats (73% vs 45%, p=0.002). NV was more severe in CR rats than HSD rats (p=0.0001). Both CR and HSD rats had similar ratios of vascularized to total retinal areas. In AIR rats, the incidence of NV was similar between CR and HSD rats (33% vs 34%, p=0.91). There was no significant difference in the severity of NV. The ratio of vascularized to total retinal area was larger in CR rats than HSD rats (73% 10% vs 68% 12%, p<0.05). Conclusion: Sprague-Dawley rats obtained from two independent commercial sources differed in their incidence and severity of NV in OIR, but not in AIR. Future genetic studies are warranted to investigate the differences between CR and HSD Sprague-Dawley rats, which might yield further clues into the pathogenesis of ROP.

Keywords: 572 retinopathy of prematurity • 566 retinal neovascularization • 316 animal model