A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat

PURPOSE. TO examine changes in the retinal vasculature of rat pups after 14 days of minute-by-minute small variations in oxygen. METHODS. Arterial oxygen data from a preterm infant who developed severe re tinopathy of prematurity (ROP) was translated to equivalent values for the rat. Newborn rat pups were raised for 14 days in a cage in which a computer controlled the atmosphere to mimic the fluctuating oxygen profile (group V ). Positive controls (P) of 12-hour cycles of 80% and 21% were run concurre ntly, as were room air controls (C). AU were killed at day 14. RESULTS. Groups V and P had significantly larger avascular retinal areas th an C [median, interquartile range (IQR): 1.7%, 0-7.9%; 10%, 8.1-13%; 0%, 0- 0%, respectively; each group n = 30]. Group P had a higher capillary branch count than C (median, IQR: 310/mm(2); 253-311 mm(2); versus 277/mm(2), 272 -364/mm(2), respectively), but this was not significant using a multilevel analysis. Group V had significantly reduced capillary counts compared with C (median, 261/mm(2); IQR, 215-290/mm(2); P < 0.05 multilevel analysis). No neovascularization was seen in any group, though abnormal terminal vessels were seen at the avascular/vascular retina interface in 73% of rats in gro up P and 21% of rats in group V. In situ hybridization on serial sections d emonstrated VEGF in the inner nuclear layer of the retina in P and V, where as C showed trace levels only. CONCLUSIONS. The vase-obliterative stage of ROP can be induced in rats usin g clinically relevant oxygen levels.