Specificity of subnormal ΔP_O2 for retinal neovascularization in experimental retinopathy of prematurity

PURPOSE. To test the hypothesis that in an experimental model of retinopathy of prematurity (ROP) rat pups that are at risk for but do not have retinal neovascularization (NV) exhibit a normal oxygenation response to a hyperoxic inhalation challenge. METHODS. Newborn Sprague-Dawley rats were raised under two varied oxygen conditions (50/10 or 40/15, indicating percent of oxygen in the air on alternate days) for 14 days and then allowed to recover in room air. Functional magnetic resonance imaging was used to determine the retinal oxygenation response (increase in partial oxygen pressure in the vitreous over the room air value, of ΔP_O2, in mm Hg) to hyperoxic inhalation challenge. Adenosine diphosphatase (ADPase)-stained retinas were analyzed to determine the NV incidence and severity. RESULTS. On postnatal day (P)20, the 40/15 procedure produced significantly (P < 0.05) lower incidence of NV than the 50/10 protocol (8% vs. 99%, respectively). Retinal ΔP_O2 during carbogen breathing of the 40/15 animals that did not have evidence of NV was not different (P > 0.05) from that of normal age-matched animals; later time points were not examined. At P26 and P34, in 50/10 rats that no longer had NV, retinal ΔP_O2S during carbogen breathing were significantly (P < 0.05) lower than that of age-matched control pups. At P34 in control rats, but not in 50/10 rats, ΔP_O2 was 61% greater (P < 0.05) during carbogen breathing than during oxygen breathing. CONCLUSIONS. The results from 40/15 experiments, together with the authors' previous data in 50/10 rats, which documented subnormal retinal ΔP_O2 before and during NV, provides additional support that subnormal retinal oxygenation to an inhalation challenge is an important event associated with the development of NV. In addition, 50/10 rats that no longer demonstrated NV had a persistent subnormal retinal ΔP_O2, suggesting a continuing risk of development of additional retinal complications after resolution of the NV in ROP.