Correction of early subnormal superior hemiretinal ΔPO₂ predicts therapeutic efficacy in experimental diabetic retinopathy

PURPOSE. To test the hypothesis that regional retinal oxygenation responses to a hyperoxic inhalation challenge are associated with reported retinopathy outcomes after different therapies in rat models of diabetic retinopathy. METHODS. Six groups of rats were maintained for 3 months: controls (n = 8), untreated diabetic (n = 8), aminoguanidine (AMG)-treated diabetic (2.5 g/kg of diet; n = 6), untreated galactosemic (n = 7), AMG-treated galactosemic (n = 10), and WAY-509-treated (25 mg/kg body weight per day) galactosemic (n = 7). After 3 months, the change in oxygen tension was measured noninvasively from the superior to the inferior ora serrata, using a novel functional magnetic resonance imaging (fMRI) technique and a carbogen (a gas mixture of 5% carbon dioxide and 95% oxygen that has been used clinically, instead of 100% oxygen, to minimize the vasoconstrictive effects of pure O₂ on retinal blood flow and oxygenation) inhalation challenge. Retinal morphometric measurements were also obtained, RESULTS. Retinal lesions (acellular capillaries and pericyte ghosts) were not significantly (P > 0.05) present at 3 months in any experimental groups compared with the control group, Superior but not inferior hemiretinal change in partial pressure of oxygen (ΔAPO₂) became significantly subnormal (P < 0.05) at 3 months of diabetes or galactosemia. Aminoguanidine, which has been found to inhibit the development of retinopathy in diabetic but not galactosemic rats, inhibited the development of a subnormal ΔPO₂ in diabetes but not in galactosemia. WAY-509, which has been reported to inhibit retinopathy in galactosemic rats, inhibited the ΔPO₂ defect in galactosemic rats. CONCLUSIONS. An early subnormal superior hemiretinal ΔPO₂ after treatment appears to be a good predictor of the risk of development of retinopathy, as well as for assessing therapeutic efficacy in experimental diabetic retinopathy.