Acute systemic 11-cis-retinal intervention improves abnormal outer retinal ion channel closure in diabetic mice

PURPOSE: To test the hypothesis that in dark-adapted diabetic mice subnormal manganese uptake in the outer retina can be ameliorated with exogenous 11-cis-retinal intervention. METHODS: Three groups were studied: age-matched controls and mice that had been diabetic for 3 months with and without acute, systemic 11-cis-retinal treatment administered 30 min before the manganese injection. Mice in each group were examined with manganese-enhanced magnetic resonance imaging (MEMRI) to assess central intraretinal manganese uptake and extraocular muscle manganese uptake. Bodyweights and glycated hemoglobin were determined. RESULTS: Both diabetic groups had lower bodyweights and higher glycated hemoglobin levels relative to controls; no differences in these parameters between diabetic groups were noted. No substantial differences in muscle uptake were noted between any of the groups. Diabetes produced a subnormal intraretinal uptake of manganese; acute exogenous 11-cis-retinal significantly corrected only outer retinal uptake, although not to control levels. CONCLUSIONS: The present results provide for the first time evidence that raises the possibility of a critical role of 11-cis-retinal, a key participant of the visual cycle, in diabetes-evoked outer retinal dysfunction.