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D. Everhart, Y. Umino, N. Cuenca, K. Cusato, R. B. Barlow; Degeneration and Regeneration of Retinal and Visual Function in Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3659.
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© ARVO (1962-2015); The Authors (2016-present)
Rescue retinal and visual losses in aged, chronically hypoglycemic Gcgr-/- mice.
Examined retinal function, visual function, and retinal anatomy of C57BL/6J mice rendered chronically hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr, prior to (12.5 months) and following (13.5 months) initiation of a high carbohydrate diet. Measured retinal function by electroretinograms (ERGs), visual acuity and contrast sensitivity by optomotor behavior, and retinal anatomy using immunofluorescence confocal microscopy. After measuring visual losses of mice at 12.5 months, mice were placed on a high carb diet. For single animal controls, single eyes were enucleated from a subset of the test population.
Hypoglycemic Gcgr-/- mice display progressive, age-related losses in visual function, retinal sensitivity, and retinal structure. From 9 to 13 months acuity and contrast sensitivity decline and retinal function decreases over 100-fold. Losses correlate with the extent of hypoglycemia. Both the inner and outer nuclear layers show modest (~20%) reductions of photoreceptor and rod bipolar cells. Horizontal cells decrease ~30%. Reduction (~50%) and altered localization of photoreceptor ribbon synapses are robust. High carb diet initiated at 12.5 months restored retinal and visual function to near normal levels by 13.5 months.
Hypoglycemia-induced losses in retinal and visual function can be restored by induction of euglycemia. We conclude that the photoreceptor-bipolar cell synapse is exceptionally sensitive to changes in metabolism. Modulation of retinal structure and function by metabolic environment has potential implications for retinal disease.
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