Diabetic macular edema (DME) is a major factor contributing to visual disabilities in diabetic patients, and the number of patients is increasing. Animal models play a key role in the development of novel therapies. In this study, pathophysiological analyses of ocular lesions in Spontaneously Diabetic Torii (SDT) fatty rats were performed. First, vascular endothelial growth factor (VEGF) concentrations in vitreous humor, retinal vascular permeability and retinal thickness were measured in SDT fatty rats (Experiment 1). Furthermore, the pharmacological effects of two anti-diabetic drugs, phlorizin and pioglitazone, on retinal lesions were evaluated (Experiment 2). As results, the SDT fatty rats exhibited VEGF increase in vitreous humor at 8 and 16 weeks of age, and both retinal vascular hyperpermeability and retinal thickening at 16 weeks of age. In particular, the layers between the retinal internal limiting membrane and the outer nuclear layer were thickened. Phlorizin treatment from 4 to 16 weeks of age improved hyperglycemia and normalized retinal thickness; however, the effect of pioglitazone on retinal thickness was not strong despite the normalization of hyperglycemia. These data demonstrate that the male SDT fatty rat is a useful model for developing new therapeutic approaches in DME., Y. Motohashi, Y. Kemmochi, T. Maekawa, H. Tadaki, T. Sasase, Y. Tanaka, A. Kakehashi, T. Yamada, T. Ohta., and Obsahuje bibliografii
Nonalcoholic steatohepatitis (NASH) is a current health issue since the disease often leads to hepatocellular carcinoma; however, the pathogenesis of the disease has still not been fully elucidated. In this study, we investigated the pathophysiological changes observed in hepatic lesions in STAM mice, a novel NASH model. STAM mice, high fat-diet (HFD) fed mice, and streptozotocin (STZ) treated mice were prepared, and changes over time, such as biological parameters, mRNA expression, and histopathological findings, were evaluated once animal reached 5, 7, and 10 weeks of age. STZ mice presented with hyperglycemia and an increase in oxidative stress in immunohistochemical analyses of Hexanoyl-lysine: HEL from 5 weeks, with fibrosis in the liver also being observed from 5 weeks. HFD mice presented with hyperinsulinemia from 7 weeks and the slight hepatosteatosis was observed at 5 weeks, with changes significantly increasing until 10 weeks. STAM mice at 10 weeks showed significant hepatic changes, including hepatosteatosis, hypertrophic hepatocytes, and fibrosis, indicating pathological changes associated with NASH. These results suggested that the increase in oxidative stress with hyperglycemia triggered hepatic lesions in STAM mice, and insulin resistance promoted lesion formation with hepatic lipid accumulation. STAM mice may be a useful model for elucidating the pathogenesis of NASH with diabetes.
Spontaneously Diabetic Torii (SDT) fatty rats, a new obese diabetic model, reportedly presented with features of non-alcoholic steatohepatitis (NASH) after 32 weeks of age. We tried to accelerate the onset of NASH in SDT fatty rats using dietary cholesterol loading and noticed changes in the blood choline level which is expected to be a NASH biomarker. Body weight and biochemical parameters were measured from 8 to 24 weeks of age. At 16, 20, 24 weeks, pathophysiological analysis of the livers were performed. Hepatic lipids, lipid peroxides, and the expression of mRNA related to triglyceride (TG) synthesis, inflammation, and fibrosis were evaluated at 24 weeks. Hepatic fibrosis was observed in SDT fatty rats fed cholesterol-enriched diets (SDT fatty-Cho) from 16 weeks. Furthermore, hepatic lipids and lipid peroxide were significantly higher in SDT fatty-Cho than SDT fatty rats fed normal diets at 24 weeks. Hepatic mRNA expression related to TG secretion decreased in SDT fatty-Cho, and the mRNA expression related to inflammation and fibrosis increased in SDT fatty-Cho at 24 weeks. Furthermore, SDT fatty-Cho presented with increased plasma choline, similar to human NASH. There were no significant changes in the effects of feeding a cholesterol-enriched diet in Sprague-Dawley rats. SDT fatty-Cho has the potential to become a valuable animal model for NASH associated with type 2 diabetes and obesity., Y. Toriniwa, M. Muramatsu, Y. Ishii, E. Riya, K. Miyajima, S. Ohshida, K. Kitatani, S. Takekoshi, T. Matsui, S. Kume, T. Yamada, T. Ohta., and Obsahuje bibliografii