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1 From the Department of Anatomy and Cell Biology; and the 2 Kresge Eye Institute, Wayne State University, Detroit, Michigan.
PURPOSE. To test the hypothesis that after supplemental oxygen recovery (SOR) in the newborn rat model of retinopathy of prematurity (ROP) the preretinal neovascular (NV) incidence and severity are decreased and the panretinal oxygenation ability is improved.
METHODS. Newborn rats were first raised in either room air (controls) or
variable oxygen (50%/10%) for 14 days. The experimental rats were
recovered during the next 6 days (until day 20) in either room air
(21% O2) or supplemental oxygen (28%). All
groups were then exposed to room air for an additional 6 days (until
day 26). On day 20, magnetic resonance imaging (MRI) was used to
determine the panretinal oxygenation response
(
PO2, mm Hg) to a carbogen (95%
O2/5% CO2) inhalation
challenge. On days 20 and 26, the retinas from a different
subset of control, room air–recovered, or SOR-recovered animals were
analyzed using ADPase stained or fluorescein-labeled dextran infused
retinal flatmounts.
RESULTS. On day 20, the panretinal PO2 of
the room air–recovered group (125 ± 5 mm Hg, mean ± SEM,
n = 12) was significantly (P < 0.05)
lower than that of the control group (179 ± 6 mm Hg,
n = 11). The panretinal
PO2 value for the SOR
group (87 ± 5 mm Hg, n = 7) was significantly
(P < 0.05) lower than both the room air–recovered
group and the control group. The NV incidence and severity were
significantly reduced (P < 0.05) in the SOR animals
compared with the room air–recovered animals. In contrast, on day 26
(after 6 days in room air), the NV incidence was statistically
(P < 0.05) greater in the animals that had been
exposed to SOR compared with room air–recovered animals.
CONCLUSIONS. After 28% SOR, the expected decrease in NV incidence and severity occurred but with an unexpected decrease in panretinal oxygenation ability. The present data strongly support an association between subnormal panretinal oxygenation ability and increased NV risk in the newborn rat ROP model. MRI appears to be a powerful new approach for quantitatively and noninvasively measuring retinal oxygenation and may be applicable to study other ischemic or ischemia-related retinopathies in addition to ROP, such as diabetic retinopathy, sickle cell retinopathy, macular degeneration, and glaucoma.
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