Decreased Amplitude of the Photopic Negative Response (PhNR) in the Ins2Akita Mouse Model of Type 1 Diabetes Mellitus

Diabetic retinopathy (DR) is a common, severe complication of diabetes mellitus. Current clinical detection of DR is based primarily on visible retinal vascular damage, and earlier detection of impending DR might allow earlier treatment to protect function. Recent studies in both animal models and humans with diabetes have shown that degradation of retinal ganglion cell (RGC) function occurs at an early stage, before visible vascular complications and before significant RGC loss. The photopic negative response (PhNR), obtained from full‐field electroretinogram (ERG) with photopic stimuli is thought to arise directly from RGC activity. Here, we hypothesized that PhNR amplitudes are reduced in a type 1 diabetic mouse model, the Ins2Akita mouse, which develops hyperglycemia by 5 weeks of age and visual function and ocular blood flow deficits early in the disease progression, before overtly visible vascular damage. Diabetic (male heterozygotes) and control (male WT littermates) mice were grouped according to age: young, adult, and old (5–6, 9–11, and 12–14 months of age, respectively). ERG recording was performed with 1.62 log cd/m 2 white flashes over a constant 40 cd.s/m 2 green background (Diagnosys Espion and ColorDome ganzfeld system) using gold ring contact lens electrodes (LKC Techniologies) under isoflurane anesthesia. Following 1 hour adaptation to the green background illumination, PhNR, a‐wave, and b‐wave amplitudes and implicit times were measured in response to 25 10‐msec flashes. The mean PhNR amplitude of the adult diabetic mice was 36% of their age‐matched controls (p < 0.01). For the old diabetic group, the mean PhNR amplitude was 49% of their age‐matched controls (p < 0.05). However, no significant difference was found in the young group. A‐wave amplitudes were decreased in the diabetic adult group, to a value only 41% of their age‐matched controls (p < 0.05). B‐wave amplitudes were decreased in the diabetic old group, to 35% of their age‐matched controls (p < 0.05). However, no significant difference was found among groups for PhNR, a‐wave, or b‐wave implicit times. Our results suggest that PhNR amplitude is altered relatively early in the Ins2Akita mouse model of diabetes. This suggests PhNR measurements could be used to detect diabetic retinopathy at earlier stages than the current clinical standard. Support or Funding Information NIH R01 EY023290 and UIWRSO Faculty Development Grant This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .