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.

Retinal Changes in Otsuka Long-Evans Tokushima Fatty Rats (Spontaneously Diabetic Rat)—Possibility of a New Experimental Model for Diabetic Retinopathy

“…10 We were able to prolong the survival of these rats up to 19 months of age, and this allowed for an examination of the details of the retina, and not only the retinal capillaries. Thus it is expected to be a good strain for the study of chronic diabetic complications.…”

Changes in Interleukin 18 in the Retinas of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes

“…In addition, our previous studies have shown that a delay in corneal wound healing, lens opacification via IL-18 and IFN-γ expression and retinal damage can be observed in 60-week-old OLETF rats 48 50 , and Miyamuraet al 50 have demonstrated the usefulness of OLETF rats as a model of diabetic retinal disease. The basement membranes of the retinal capillaries of 56-week-old OLETF rats are significantly thicker than in LETO rats, and the ratio of the pericyte area to the capillary cross-section area is significantly lower.…”

Effect of High Glucose Levels on Amyloid β Production in Retinas of Spontaneous Diabetes Mellitus Otsuka Long-Evans Tokushima Fatty Rats

“…However, the degree of hyperglycemia and insulin resistance in high-fat diet-induced obese rats is lower than that in OLETF rats, and it is difficult to observe the onset of ocular diabetic complications. [26][27][28] Miyamura et al 26) have demonstrated the usefulness of the OLETF rat as the model of diabetic retinal disease. In the retinal capillaries of 56-week-old OLETF rats, basement membranes are significantly thicker, and the ratio of the pericyte area to the capillary cross-section area is significantly lower than in controls.…”