Larger animals, including dog, cats, and pigs, have been used in DR research with relative success, but not exempt from limitations. All of these models, although morphologically similar to human DR, tend to be expensive and complex because of the lack of specific antibodies and molecular biology reagents. To add more, techniques for manipulation and genetic characterization are somewhat experimental and therefore less precise than in small animal models. Indeed, nonhuman primates stand out among other models discussed above because of the presence of a macula. Cynomolgus monkeys (Macaca fascicularis) that were pancreatectomized or treated with streptozotocin and obese rhesus monkeys (Macaca mulatta) that spontaneously develop diabetes at middle age have been used in DR studies. As in humans, DR develops fairly slowly in these models. Johnson et al. reported ophthalmoscopical changes in aged monkeys with spontaneous diabetes. Their findings showed intraretinal hemorrhages and large areas of retinal capillary nonperfusion along with macular edema (287). These models can almost perfectly mimic every aspect of the human condition. However, the longer gestational periods, the lack of reagents for experimentation, the high cost of maintenance, and the ethical issues involved represent disadvantages that cannot be ignored.

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