Microvascular retinopathy in the Zucker diabetic fatty rat.

PURPOSE To determine if quantifiable morphometric signs of retinopathy occur in the Zucker diabetic fatty rat (ZDF/Gmi-fa, formerly designated ZDF/Drt), a partially inbred strain in which the genetic propensity for diabetes is only expressed in obese males. METHODS Retired diabetic (ZDF/Gmi-fa) and control lean Zucker (fa/+) breeder rats were examined for quantifiable evidence of microvascular changes of the retinal capillaries by gross examination, trypsin digestion of retinal vessels, and transmission electron microscopy. RESULTS Gross examination of retinas and trypsin digestion of capillaries revealed no differences. Quantitative assessment of capillary cell nuclear density showed that diabetic retinas were hypercellular compared to lean rats (3.888 +/- 0.041 versus 3.304 +/- 0.046 nuclei per 100 microns (mean +/- SE), P = 0.0042). Transmission electron microscopic analysis of retinal capillary basement membrane thickness demonstrated thicker measurements in diabetic animals (mean thickness 21% greater in diabetic rats, P = 0.0307). CONCLUSIONS This model may be useful for pharmacologic intervention studies because it is naturally and severely non-insulin-dependent diabetic, there are quantifiable retinal vascular changes, and same-sex litter mates can be used as controls.