Differences between rat strains in models of retinopathy
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Purpose: Genetic factors appear to modulate the incidence and severity of retinopathy of prematurity (ROP). Different rat strains may be analogous to genetic ...
Molecular Vision 2005;11:524-30 Received 16 July 2004 | Accepted 26 May 2005 | Published 19 July 2005
Differences between rat strains in models of retinopathy of prematurity Beth N. I. Floyd,1 David A. Leske,2 Siobhan M. E. Wren,2 Martina Mookadam,2 Michael P. Fautsch,2 Jonathan M. Holmes2 1
Mayo Medical School and the 2Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN Purpose: Genetic factors appear to modulate the incidence and severity of retinopathy of prematurity (ROP). Different rat strains may be analogous to genetic differences across human ethnic groups. We investigated the incidence and severity of neovascularization (NV) in Brown Norway (BN) and Sprague Dawley (SD) rats in oxygen-induced retinopathy (OIR) and acidosis-induced retinopathy (AIR) models for ROP. We also studied whether there was a difference in retinal vascular endothelial growth factor (VEGF) mRNA levels in OIR animals. Methods: Newborn SD and BN rats (110 in both groups) were raised in standardized litters of ten (four OIR, twelve AIR, six non-gavaged room air controls). Beginning on day 1 of life, OIR litters were exposed to seven cycles of hyperoxia (80% O2, 20.5 h) and hypoxia (10% O2, 0.5 h) with a gradual return to 80% O2 over 3 h. This was followed by room air recovery for five days. OIR and OIR control rats were sacrificed on day 13 of life. AIR rats were gavaged twice daily with NH4Cl (10 mmol/kg) from day 2 to day 7 of life, or 15 mmol/kg twice daily on day 2 and then 10 mmol/kg twice daily from day 3 to day 7. AIR and AIR control rats were sacrificed on day 10 or day 13. Retinas from left eyes were dissected, ADPase stained and flatmounted. Presence and severity of NV (clock hours, 0 to 12) was scored by a masked observer. Right retinas from OIR and room air controls were processed for VEGF mRNA analysis. Results: In OIR rats, the incidence of NV was higher in BN than SD rats (100% compared to 5%, p
