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D. Everhart, Y. Umino, N. Cuenca, K. Cusato, R. Barlow; Rescue of Vision in Hypoglycemic Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4489.
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To determine the effectiveness of diet-induced euglycemia in preventing and rescuing visual and retinal sensitivity and retinal structure in chronically hypoglycemic Gcgr-/- mice.
C57BL/6J mice rendered chronically hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr, were placed on a high carbohydrate diet either prior to detectable retinal and visual losses (6 months old) or following substantial losses (12.5 months old). Retinal function was measured by electroretinograms (ERGs), visual acuity and contrast sensitivity were quantified by optomotor behavioral methods, and retinal anatomical changes were imaged using immunofluorescence confocal microscopy.
Gcgr-/- micedisplay progressive, age-related losses in visual function and in retinal structure and sensitivity with eventual retinal cell death. Their retinal and visual function decrease over 100-fold and 30% respectively from 9 months to 13 months of age and losses correlate with the extent of hypoglycemia, regardless of genotype. Regarding structure, older untreated Gcgr-/- mice exhibit ~20% reduction in rod bipolar cells (protein kinase c antibody) and show an ~50% loss and altered localization of their ribbon synapses (bassoon antibody). Gcgr-/- mice younger than 6 months have normal retinal and visual function. Placing them on a high carbohydrate diet induces euglycemia and prevents the aged-related vision loss noted above. Surprisingly, placing mice on a high carbohydrate diet restores their retinal and visual function (12.5 month old) and rescues their retinal structure.
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