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

B. A. Berkowitz, Y. Ito, T. S. Kern, C. McDonald, R. Hawkins

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2964-2969
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number12
Publication statusPublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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