Retinal capillary changes in Otsuka Long-Evans Tokushima fatty rats - (Spontaneously diabetic strain) - Electron-microscopic study

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a spontaneously diabet ic strain with polyuria, polydipsia and mild obesity. The pathological feat ures of OLETF rats closely resemble those of patients with noninsulin-depen dent diabetes mellitus. The purpose of this study is to investigate the ret inal capillary changes in the OLETF rat and to confirm the valuability of t he OLETF rat as the model of diabetic retinal disease. One-month-old male O LETF rats and age- and sex-matched Long-Evans Tokushima Otsuka (LETO) contr ols were supplied by Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). Bod y weight and blood sugar levels were measured monthly. Their eyes were enuc leated 14 months after birth. Ultrathin sections were made and examined wit h a transmission electron microscope. According to their location, two kind s of retinal capillaries were differentiated: those in the nerve fiber laye r (NFL) and those in the outer plexiform layer (OPL). The image of each cap illary was transferred to a computed image analyzer, and basement membrane thickness and the ratio of the pericyte area to total capillary cross-secti on area were determined. Corrosion casts of retinal vessels were made and e xamined with scanning electron microscopy (SEM). OLETF rats gained more wei ght than LETO rats from the beginning, and the difference increased gradual ly with age. The blood sugar level of OLETF rats was higher than that of LE TO rats after 5 months of age, In the retinal capillaries of 14-month-old O LETF 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 i n NFL, 0.111 +/- 0.102 in OPL; LETO: 0.288 +/- 0.142 in NFL, 0.198 +/- 0.13 6 in OPL), The endothelial cell cytoplasm had degenerated. SEM examination of the vascular corrosion cast of a 14-month-old OLETF rat showed caliber i rregularity, 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 m odel for the study of ocular diabetic complications in humans.