Retinal neovascularization has not been observed to date in diabetic primates. Whether or not retinal neurons degenerate in diabetic primates has not been reported.

Therapies Studied in this Model

None.

Advantages and Disadvantages of the Model

A major advantage of the primate model is the presence of a macula, which is lacking in nonprimate models. As can be seen from the studies conducted to date, however, the development of retinopathy is slow and variable between animals. The retinopathy that has been detected is most similar to the early to midstages of retinopathy in patients, and neovascularization has not been observed. The ethical issues related to use of primates, the expenses associated with their maintenance, slow development of pathology, and lack of availability of molecular regents have not favored use of this model.

DIABETIC DOGS

Type of Diabetes

Studies to date of diabetic dogs have focused on type 1 diabetes, the diabetes being induced by injections of alloxan, streptozotocin, or growth hormone, or by pancreatectomy. No long-term studies have been reported using dogs having type 2 diabetes.

Histopathology and Rate of Development of Retinopathy

The retinopathy which develops in diabetic dogs includes saccular capillary microaneurysms (MA), degenerate (acellular and nonperfused) capillaries (AC), pericyte ghosts (PG), varicose and dilated capillaries (or intraretinal microvascular abnormalities (IRMAs) ), and dot and blot hemorrhages (9–12). Several of these vascular lesions are illustrated in Fig. 1. Arteriolar smooth muscle cell loss also has been observed in diabetic dogs (13, 14), just as it has been described in diabetic humans. There is a long interval before retinopathy becomes manifest in diabetic dogs (just as in diabetic humans), but in general, dogs do seem to develop retinal histopathology in diabetes sooner than do diabetic patients. After about 2 years of hyperglycemia in diabetic dogs, increasing numbers of retinal capillaries come to possess endothelial cells but few or no pericytes, and microaneurysms begin to appear soon after. Within 5 years of insulindeficient diabetes, all dogs with chemically induced diabetes have retinopathy.

Neovascularization has been observed to develop in diabetic dogs, albeit only within the retina and not in preretinal vitreous (15). Whether or not retinal neurons die in diabetes has not been reported.

Therapies Studied in this Model

Improved glycemic control from the onset of diabetes (for 5 years) was found to significantly inhibit the development of retinopathy in diabetic dogs (16, 17). Instituting good glycemic control after a prior period of poor glycemic control, however, was