Spatial frequency threshold and contrast sensitivity of an optomotor behavior are impaired in the Ins2Akita mouse model of diabetes

Abstract

Diabetic retinopathy can lead to progressive loss of vision and is a leading cause of blindness. The Ins2(Akita) mouse model of diabetes develops significant retinal and systemic pathology, but how these affect visual behavior is unknown. Here, we show that Ins2(Akita) mice have progressive, quantifiable vision deficits in an optomotor behavior. This mouse line is a promising model in which to understand the contribution of retinal neuronal injury during the chronic hyperglycemia and hypoinsulinemia of diabetes to deficits in vision.

Figure 1

Ins2^Akita mice have significant deficits in spatial frequency threshold and contrast sensitivity in an optomotor task at 5 and 7.5 months of age but not at 2.5 months of age. Diabetic male mice heterozygous for the Akita allele (“diab” or “d”) were compared to control littermate mice (“ctrl” or “c”) for head tracking responses to horizontally drifting vertical sinusoidal gratings. The spatial frequency threshold of the behavior was determined as the maximum spatial frequency at maximum contrast that still induced smooth head tracking movements (top panel). Note that the axis begins at 0.28 cyc/deg. The minimum contrast that still induced these movements—i.e., the contrast threshold, the reciprocal of which is the contrast sensitivity—was also determined at 0.064 cyc/deg (middle panel) and 0.103 cyc/deg (lower panel). Boxes, bounded by the first and third quartiles, also show the median (black line). Box plot whiskers are drawn to 1.5 times interquartile distance. Outliers are shown as open circles. By all three measures, Ins2^Akita mice diabetic for at least 4 months were deficient (*, p<0.05; **, p<0.01; ***, p<0.001).

Figure 2

The combined spatial frequency thresholds (top panel) of 5 month old (open circles) and 7.5 month old (open triangles) Ins2^Akita mice were correlated to blood glucose levels while contrast sensitivities at 0.103 cyc/deg (bottom panel) were not. Linear fits to the data are also shown (black lines). Contrast sensitivity data at 0.064 cyc/deg was essentially identical and is not shown. The average age of the mice at blood glucose determination was 8 weeks.