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G. Reddy, S. Palla, S. Natarajan, M. A. Patil, P. Lopamudra, N. V. Giridharan; Exploration of a Suitable Induced Type-2 Diabetic Rodent Animal Model to Study Diabetic Ocular Complications. Invest. Ophthalmol. Vis. Sci. 2010;51(13):115.
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Background: Prolonged exposure to chronic hyperglycemia during diabetes can lead to various complications including cataract and retinopathy. Type-2 diabetes (T2D) is the most common form of diabetes and it accounts for 90-95% of diabetic cases when compared to type-1 diabetes (T1D). Efforts have been on to understand the pathophysiology of diabetes-induced cataract and retinopathy in experimental animals. However, apart from genetic models, most of the studies are conducted on induced-T1D models. Considering the limitations of extrapolating T1D animal model data to T2D-induced diabetic complications, we have made an attempt to develop and evaluate a suitable animal model to study T2D-induced complications, mainly diabetic cataract and retinopathy.
Evaluated neonatal-streptozotocin (nSTZ)-induced T2D in three different rat strains, WNIN, SD and WNIN-GR-Ob, by injecting STZ (45-90 mg/kg body weight) to two-day-old pups. Fasting blood glucose and insulin levels were monitored at regular intervals. Development of cataract and retinopathy was assessed by slit-lamp biomicroscope and indirect ophthalmoscope. Insulin resistance (IR) was assessed at regular intervals by performing oral glucose tolerance test (OGTT). After experimental period, the effect of IR and/ or hyperglycemia on biochemical changes in eye lens and retina were monitored.
Although, WNIN and SD rats showed IR and marginally increased levels of fasting glucose at the age of 3-4 months, they have neither developed frank hyperglycemia and nor cataract even after 8 months of STZ-injection. However, WNIN-GR-Ob rats developed hyperglycemia at the age of one month and showed a gradual increase in glucose levels up to three months and persisted till the end of the experimental period (five months). Interestingly, WNIN-GR-Ob rats have developed cataract by 3 months and showed signs of retinopathy by the age 5 months.
Morphological, biochemical and molecular analysis supports that nSTZ- WNIN-GR-Ob rat could serve as model to study molecular basis of T2D-induced ocular complications and which may be useful to develop preventive/ therapeutic strategies.
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