Early changes in retinal function in rat models of Type I and Type II diabetes

Abstract

Purpose : Previously, we confirmed that a high fat diet (HFD) + low dose STZ (30 mg/kg) treatment can be used to model Type II diabetes in rats. Some HFD + low STZ rats exhibited a moderate diabetic state and typical early retinal deficits, while others exhibited a more severe metabolic phenotype that mimics Type I diabetes. Here, we investigated visual and retinal function in Type I and Type II diabetic rats.

Methods : Adult male Long Evans rats were assigned to one of the following groups: Control (n=12) that received normal rat chow, HFD only (n=14), and HFD+STZ (n=17). Diabetic rats were stratified into Type I (n=8) and Type II (n=9) after assessing weights, glucose and insulin tolerance, fed and fasted blood glucose, and blood insulin levels (via ELISA). Visual function was assessed using optomotor response (OMR) every 2 weeks, beginning 2 weeks before HFD. We evaluated retinal function using electroretinogram oscillatory potentials (OPs) every 4 weeks.

Results : Blood glucose was significantly different in Type I (385.1 mg/dL) and Type II rats (159.3 mg/dL; p<0.0001). Type I rats showed severe impairments in insulin and glucose tolerance along with reduced body weight (11%) and very low insulin levels (0.43 ng/mL). In contrast, Type II rats showed moderate impairment in insulin and glucose tolerance with weights and insulin levels (3.76 ng/mL) similar to control (4.68 ng/mL) and HFD rats (4.72 mg/dL). Both models showed OMR deficits beginning at 4 weeks post-STZ and continuing to 8 weeks (Type I: 14%; Type II: 11%; p<0.001 for both) and delays in OP implicit times at 8 weeks (Control: 51.1± 0.7ms; Type I: 54.8 ± 1.3ms, p<0.05; Type II: 57.2 ± 1.1ms, p<0.01). HFD only rats showed smaller OMR (6%, p<0.001) and OP deficits (53.2 ± 1.1ms, n.s.) at 8 weeks.

Conclusions : Type I and Type II HFD+STZ rats exhibit similar retinal deficits with diabetes despite differences in metabolic measures. These data indicate that 4 weeks of hyperglycemia is sufficient to reduce visual function, regardless of hyperglycemia severity.

This is a 2020 ARVO Annual Meeting abstract.