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Steve Cunningham, Janet R. McColm, Jean Wade, Kofi Sedowofia, Neil McIntosh, Brian Fleck; A Novel Model of Retinopathy of Prematurity Simulating Preterm Oxygen Variability in the Rat. Invest. Ophthalmol. Vis. Sci. 2000;41(13):4275-4280.
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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
retinopathy 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 concurrently, as were room air controls (C). All
were killed at day 14.
results. Groups V and P had significantly larger avascular retinal areas than 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/mm2; 253–311 mm2; versus
277/mm2, 272–364/mm2, respectively), but this
was not significant using a multilevel analysis. Group V had
significantly reduced capillary counts compared with C (median,
261/mm2; IQR, 215–290/mm2; 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 group P and 21% of rats in group V. In situ hybridization on
serial sections demonstrated VEGF in the inner nuclear layer of the
retina in P and V, whereas C showed trace levels only.
conclusions. The vaso-obliterative stage of ROP can be induced in rats using
clinically relevant oxygen levels.
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