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PO2 Predicts Therapeutic Efficacy in Experimental Diabetic Retinopathy
1 From the Department of Anatomy and Cell Biology and the 2 Kresge Eye Institute, Wayne State University, Detroit, Michigan; and the 3 Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
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
(
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 galactosemic rats,
inhibited the development of a subnormal PO2 in diabetes
but not in galactosemia. WAY-509, which has been reported to inhibit
retinopathy in galactosemic rats, inhibited the PO2
defect in galactosemic rats.
CONCLUSIONS. An early subnormal superior hemiretinal PO2 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.
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