Retinal Capillary Changes in Otsuka Long-Evans Tokushima Fatty Rats (Spontaneously Diabetic Strain)

Abstract

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a spontaneously diabetic strain with polyuria, polydipsia and mild obesity. The pathological features of OLETF rats closely resemble those of patients with non-insulin-dependent diabetes mellitus. The purpose of this study is to investigate the retinal capillary changes in the OLETF rat and to confirm the valuability of the OLETF rat as the model of diabetic retinal disease. One-month-old male OLETF rats and age- and sex-matched Long-Evans Tokushima Otsuka (LETO) controls were supplied by Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). Body weight and blood sugar levels were measured monthly. Their eyes were enucleated 14 months after birth. Ultrathin sections were made and examined with a transmission electron microscope. According to their location, two kinds of retinal capillaries were differentiated: those in the nerve fiber layer (NFL) and those in the outer plexiform layer (OPL). The image of each capillary was transferred to a computed image analyzer, and basement membrane thickness and the ratio of the pericyte area to total capillary cross-section area were determined. Corrosion casts of retinal vessels were made and examined with scanning electron microscopy (SEM). OLETF rats gained more weight than LETO rats from the beginning, and the difference increased gradually with age. The blood sugar level of OLETF rats was higher than that of LETO rats after 5 months of age. In the retinal capillaries of 14-month-old OLETF rats, basement membranes were significantly thicker (OLETF: 209 ± 51 nm in NFL, 132 ± 23 nm in OPL; LETO: 118 ± 28 nm in NFL, 79 ± 14 nm in OPL), and the ratio of pericyte area to the capillary cross-section area was significantly lower than that of the controls (OLETF: 0.131 ± 0.92 in NFL, 0.111 ± 0.102 in OPL; LETO: 0.288 ± 0.142 in NFL, 0.198 ± 0.136 in OPL). The endothelial cell cytoplasm had degenerated. SEM examination of the vascular corrosion cast of a 14-month-old OLETF rat showed caliber irregularity, narrowing, tortuosity and loop formations of capillaries. The morphological changes in the retinal capillaries of OLETF rats were similar to those seen in diabetic patients. The OLETF rat may be a useful animal model for the study of ocular diabetic complications in humans.