Examination of the retinal vasculature in Obese Koletsky (SHROB) rats demonstrated degeneration and loss of intramural pericytes and extensive capillary dropout after 3 months of age in lean and obese rats, with more frequent pathology in the obese rat (69, 70). Retinal capillary dropout is severe and progressive, resulting in some cases in preretinal neovascularization after 6–12 months of age (70). No microaneurysms and retinal hemorrhages were found. These reports were only descriptive, with no quantitative or mechanistic studies to explain the histopathology.

After 24 weeks consuming a 54% sucrose diet, increased numbers of pericyte ghosts and endothelial cells were detected in the obese, spontaneously hypertensive/NIH-corpulent rat strain (SHR/N-cp) compared to lean, nondiabetic controls fed with sucrose diet (71). At 6 months of age, the males of the spontaneously hypertensive/McCune-corpulent rat (SHR/ N:Mcc-cp) showed increased E/P ratio, increased basement membrane thickness, and capillary obstruction (35). Acellular capillaries and pericyte ghosts also were detected in these animals but were not quantified in this study. The BBZDP/Wor strain has been reported to develop pericyte loss and retinal capillary basement thickening (58).

Neuronal disease

Rats having insulin-deficient diabetes lose retinal ganglion cells (39, 56, 72–81), and this neurodegeneration has been detected as early as 1 month of diabetes (75). It has been postulated that this early neurodegeneration might contribute to the pathogenesis of the vascular pathology, but Nepafenac, a COX inhibitor, inhibited diabetes-induced degeneration of retinal capillaries while having no effect on the loss of retinal ganglion cells (81). Neurodegeneration has not been studied in models of type 2 diabetes to date.

Therapies or Gene Modifications Studied in this Model

Rats have been used in a variety of studies on the effects of therapy on development of diabetic retinopathy (Table 2). Most of these studies have been conducted using chemically induced diabetic models, and for durations of diabetes of less than one year.

Advantages and Disadvantages of the Model

Rats have been the most commonly used models of diabetic retinopathy. They develop at least the early stages of the retinopathy within only months of diabetes, are inexpensive to house, and easy to handle, and reagents (including antibodies) are widely available. Potential disadvantages of this model are the rapid onset of cataract which develops in diabetes and can limit visibility of the fundus, and the inability to genetically modify rats at present.

DIABETIC MICE

Type of Diabetes

Type 1 diabetes

Studies of retinopathy using mouse models of type 1 diabetes have utilized chemically induced diabetes or, recently, the spontaneous diabetes of the Ins2Akita mouse. The Ins2Akita mouse contains a dominant point mutation in the insulin 2 gene that induces spontaneous type 1 diabetes, especially in males (88).