Preservation of Vision in Hypoglycemic Mice via Diet

Abstract

Purpose:: To test effectiveness of diet-induced euglycemia in preserving vision of chronically hypoglycemic Gcgr-/- mice.

Methods:: 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.

Results:: 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.

Conclusions:: 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.

Keywords: retina • metabolism • electroretinography: non-clinical