Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities

Garlic ameliorates long-term pre-diabetes induced retinal abnormalities in high fructose fed rat model

452-460Retinopathy is one of the micro vascular complications of diabetes and can also be observed in pre-diabetic state. However, there are only limited studies available on the pathophysiology of retinopathy in pre-diabetic state and its preventive strategies. In this study, we investigated the retinal functional, structural and molecular alterations using high fructose (HF) induced pre-diabetic rat model and also the protective role of garlic. Feeding of HF to Wistar NIN (WNIN) rats had developed insulin resistance (IR) and impaired glucose tolerance (IGT) by three months, while retinal functional abnormalities by ten months as evidenced by decrease of Electroretinogram (ERG) scotopic, photopic b-wave amplitudes, oscillatory potentials (OPs) when compared to controls. Supplementation of garlic (3%) to HF+G group rats had marginally protected these changes. Elevated expression of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), aldose reductase (AR) and decreased rhodopsin (Rho) in HF group rats as evidenced by immunehistochemistry, immunoblot methods, which were further supported by gene expression studies, indicate the initiation of retinal abnormalities. Increased immune-fluorescence signal of carboxymethyl lysine (CML-KLH) and 4-hydroxynanoenol (4-HNE) in retina of HF group rats indicate the association of glycation and oxidative stress, respectively. Early intervention of garlic to HF+G group rats attenuated retinal functional, structural, and molecular abnormalities