Abstract
Abstract: :
Purpose: Neonatal rat models of retinopathy of prematurity (ROP) include oxygen–induced retinopathy (OIR) and acidosis–induced retinopathy (AIR). In humans, there are genetic differences in susceptibility to ROP (e.g. Caucasian versus African Americans). Given that Sprague Dawley (SD) and Brown Norway (BN) rats have genetic differences, we investigated the incidence and severity of neovascularization (NV) in BN and SD rats in OIR and AIR models. Methods: 70 newborn SD and 70 newborn BN rats were raised in standardized litters of 10 (4 OIR, 6 AIR, 4 non–gavaged room air controls). Beginning on day 1 of life, OIR litters were exposed to 7 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. This was followed by room air recovery for 5 days. OIR and OIR control rats were sacrificed on day 13 of life. AIR rats were gavaged twice daily with NH4Cl (20 mmol/kg bodyweight) from days 2 to 7 of life. AIR and AIR control rats were sacrificed on day 10. Retinae from left eyes were dissected, ADPase stained and flatmounted. Presence and severity of NV was scored by a masked observer. Results: In OIR rats, the incidence of NV was higher in BN than SD rats (100% vs. 5%, P<0.0001). NV was more severe in BN rats (1 to 10 clockhours, median 7 clockhours vs. 0 to 1 clockhour, P=0.0001). In contrast, for AIR rats the incidence of NV was similar in BN and SD rats (6% vs. 0%, P=1.0). One control retina of 40 (2.5%) was graded as positive for NV. Conclusions: BN rats differ from SD rats in incidence and severity of NV in OIR, but not in AIR. Future genetic studies are warranted to investigate the mechanism of differences between Brown Norway and Sprague Dawley rats in models of ROP. These genetic studies may yield further clues into the pathogenesis of ROP.
Keywords: retinal neovascularization • retinopathy of prematurity • hypoxia