Visual Acuity and Contrast Sensitivity Are Reduced in the Ins2Akita Diabetic Mouse

Abstract

Purpose: : Previously we have shown that diabetes leads to loss of retinal neurons including ganglion and amacrine cells, accompanied by changes in the dendritic morphology of surviving large ON ganglion cells, in the Ins2^Akita/+ diabetic mouse. The purpose of this study was to determine the effect of diabetes on photopic visual function in Ins2^Akita/+ mice. These experiments tested the hypothesis that visual acuity and contrast sensitivity are reduced by diabetes in Ins2^Akita/+ mice, and become progressively worse with longer durations of hyperglycemia, compared to the non-diabetic Ins2^+/+ littermates.

Methods: : Ins2^Akita/+ diabetic and Ins2^+/+ wild-type littermates (controls) were bred in specific antigen free housing. Diabetic phenotype was determined by blood glucose monitor between week 4 and week 5 after birth. A virtual optomotor system (Optomotry^TM, Cerebral Mechanics) was used to measure visual function (n=6 to 8 mice per group). Standard "staircase" protocols, as described by Prusky et al (IOVS, 2004, 45:4611-4616), were followed to determine the acuity and contrast sensitivity thresholds. Contrast sensitivity was measured at the spatial frequency of 0.064 c/d. Acuity and contrast sensitivity were measured once per day for three days and averaged for each mouse to obtain a final score for each time point in the study. At the end of the experiment the amount of retinal apoptosis was measured in each mouse using a cell death ELISA (Roche). Statistical comparisons were made by ANOVA or unpaired t-test.

Results: : Visual acuity was significantly reduced after the first month of hyperglycemia (p<0.01) in the Ins2^Akita/+ diabetic mice, compared to Ins2^+/+ controls, and did not recover as the mice aged up to 36 weeks old. Contrast sensitivity was also significantly reduced in the same animals, compared to controls, during the course of the study (p<0.01). There was significantly more cell death in the retinas of mice after 32 weeks of hyperglycemia (36 weeks old), confirming previous reports of elevated apoptosis due to diabetes.

Conclusions: : Diabetes results in reductions in acuity and contrast sensitivity in the Ins2^Akita mouse. The loss of function is apparent 1 month after the onset of significant hyperglycemia. The visual deficits may be related to previously established neurodegenerative changes in the retinas of these mice.

Keywords: diabetes • visual acuity • contrast sensitivity