Retinal changes in Otsuka Long-Evans Tokushima Fatty rats (spontaneously diabetic rat) - Possibility of a new experimental model for diabetic retinopathy

Purpose: To study retinal changes in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a spontaneously diabetic rat, and evaluate it as a possible new diabetic retinopathy model. Methods: We examined the retinas of OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats as controls under both a transmission electron microscope (TEM) and a scanning electron microscope (SEM). Results: We detected higher blood sugar level in the OLETF rats than in the LETO rats beginning at 5 months of age. The inner nuclear layers of the retina decreased from 3-4 rows to 2 rows, whereas the photoreceptor cell nuclei decreased from 8 rows to 3-6 rows. Retinal pigment epithelial cells decreased in height, and basal infoldings were poorly developed. Retinal capillary basement membranes were significantly thicker in the OLETF rats than in the LETO rats, and endothelial cell damage was observed. The SEM of vascular corrosion casts of OLETF rats showed tortuosity, microaneurysms, and loop formations. Conclusions: The development of spontaneous hyperglycemia in OLETF rats was associated with alterations in retina ultrastructure. Changes were similar to those seen in diabetic retinopathy, but did not include either hemorrhages or exudates. The OLETF rat may be a useful animal model for the study of ocular complications in humans.