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

Abstract

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.

Figure 1

The inner and outer retina of diabetic mice take up less manganese than in controls – a pattern partially corrected in the outer retina upon treatment with 11-cis-retinal. A: Representative pseudo-color spin-lattice relaxation rate (1/T1) parameter maps of control (left), diabetic (middle), and diabetic treated with 11-cis-retinal (right) mice illustrate lower uptake in diabetics, and partial correction with 11-cis-retinal treatment. Note that 1/T1 values directly reflect manganese levels [16] and greater manganese uptake is indicated by brighter retinal reds. The central retinal regions analyzed in this study are indicated by the white boxes and the extraocular muscle region-of-interest analyzed herein is illustrated in the right-most image. B: Quantitative analysis of manganese uptake in inner (left graph) and outer retina (right graph) confirms the pattern suggested by the representative images above. * indicates a significant difference (p<0.05) from control mice values; # indicates a significant difference (p<0.05) from the diabetic mice values. The error bars represent standard deviations, and numbers above the bars represent the number of animals studied.