Correction of early subnormal superior hemiretinal Delta PO2 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 retinopat hy outcomes after different therapies in rat models of diabetic retinopathy . Methods. Six groups of rats were maintained for 3 months: controls (n=8), U ntreated 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). Aft er 3 months, the change in oxy en tension was measured noninvasively from t he superior to the inferior ora serrata, using a novel functional magnetic resonance imaging (fMRI) technique and a carbogen (a gas mixture of 5% carb on dioxide and 95% oxygen that has been used clinically, instead of 100% ox ygen, to minimize the vasoconstrictive effects of pure O-2 on retinal blood flow and oxygenation) inhalation challenge. Retinal morphometric measureme nts were also obtained. Results. Retinal lesions (acellular capillaries and pericyte ghosts) were n ot significantly (P>0.05) present at 3 months in any experimental groups co mpared with the control group. Superior but not inferior hemiretinal change in partial pressure of oxygen (Delta PO2) 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 ga lactosemic rats, inhibited the development of a subnormal <Delta>PO2 in dia betes but not in galactosemia. WAY-509, which has been reported to inhibit retinopathy in galactosemic rats, inhibited the Delta PO2 defect in galacto semic rats. Conclusions. An early subnormal superior hemiretinal Delta PO2 after treatm ent appears to be a good predictor of the risk of development of retinopath y, as well as for assessing therapeutic efficacy in experimental diabetic r etinopathy.