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D. Everhart, Y. Umino, R. Hafler, J. C. Pan, T. H. Nguyen, E. T. Brown, E. Solessio, R. B. Barlow; Preservation of Vision in Hypoglycemic Mice via Diet. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1291.
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To test effectiveness of diet-induced euglycemia in preserving vision of chronically hypoglycemic Gcgr-/- mice.
Retinal function as measured by electroretinograms (ERGs), and visual acuity and contrast sensitivity as measured by optomotoral behavioral methods (Optomotry) were used to track the vision of Gcgr-/-, Gcgr +/-, and high carbohydrate diet treated Gcgr -/- mice.
C57BL/6J mice rendered hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr, display late-onset loss of retinal function, loss of visual acuity and eventual death of retinal cells. Decreases in retinal sensitivity and acuity correlate directly with the degree of hypoglycemia. Although Gcgr-/- mice have lower average blood glucose than Gcgr-/- mice, glucose levels vary over wide ranges for both genotypes. Interestingly, losses of retinal and visual function correlate directly with blood glucose phenotype regardless of genotype. Introduction of a high carbohydrate diet delays loss of vision in Gcgr-/- mice. Placing 6-month old Gcgr-/- mice on a high carbohydrate diet (an age at which they display normal retinal function) induces euglycemia and normal retinal and visual function past 13 months of age. Placing younger (3-months old) on the same high carb diet is not as effective. Experiments are underway to test whether a "critical period" exists for glucose preservation of vision in hypoglycemic mice.
Blood glucose level is the independent variable in vision loss in chronically hypoglycemic mice. Question remains whether ingested glucose and subsequent euglycemia can rescue lost vision in hypoglycemic Gcgr-/- mice.
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