Correction of early subnormal superior hemiretinal DeltaPO(2) 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 O(2) 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 (DeltaPO(2)) 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 DeltaPO(2) in diabetes but not in galactosemia. WAY-509, which has been reported to inhibit retinopathy in galactosemic rats, inhibited the DeltaPO(2) defect in galactosemic rats. CONCLUSIONS An early subnormal superior hemiretinal DeltaPO(2) 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.