Abstract
Spontaneously Diabetic Torii (SDT) fatty rat is a novel animal model of type 2 diabetes with obesity. SDT fatty rats develop hyperglycemia, dyslipidemia, and other diabetic complications including ocular disorders; however, diabetic cataract formation in SDT fatty rats has not been fully investigated. The aim of the current study was to investigate the characteristics of cataract in the SDT fatty rats. The mean body weight of SDT fatty rats is larger than that of age-matched Sprague-Dawley (SD) rats and control animals until 8 weeks of age, and thereafter the growing speed decreased until the end of observation at 16 weeks of age. Blood glucose levels in SDT fatty rats were significantly higher than those in SD rats throughout the observational period. Slit-lamp examination revealed that no rats showed cataract formation at 5 weeks of age; however, SDT fatty rats gradually developed cortical cataract and posterior subcapsular cataract, both of which are the common types of cataract in patients with type 2 diabetes. The levels of glucose, sorbitol, and fructose were higher in the lens tissues of SDT fatty rats in comparison with that of SD rats. Furthermore, the level of 4-hydroxynonenal (4-HNE) was higher in the lens of SDT fatty rats than in that of SD rats. By contrast, total glutathione (GSH) concentration was lower in the lens of SDT fatty rats than in that of SD rats. The present study demonstrated that the cataractogenesis in SDT fatty rats resembled human diabetic cataract formation, indicating that SDT fatty rats serve as a potential animal model in researches on human cataract associated with type 2 diabetes and obesity.
Highlights
The prevalence of diabetes is increasing worldwide, with an estimated global prevalence of 463 million in 2019, and with a projected upsurge affecting 578 million people by 2030 and 700 million people by 2045 [1]
Cortical cataract and posterior subcapsular cataract (PSC) were the main types of lens opacification in Spontaneously Diabetic Torii (SDT) fatty rats, both of which are the characteristic phenotypes of cataract in patients with type diabetes
Reduced antioxidant GSH and elevated 4-HNE, an oxidative stress marker, were observed in the lens of SDT fatty rats. These findings indicate that SDT fatty rats serve as a spontaneous diabetic animal model in order to investigate the detailed molecular mechanisms of diabetic cataract formation
Summary
The prevalence of diabetes is increasing worldwide, with an estimated global prevalence of 463 million in 2019, and with a projected upsurge affecting 578 million people by 2030 and 700 million people by 2045 [1]. Diabetes is associated with an increased risk of visual disturbance due to ocular complications including cataract, retinopathy, and neovascular glaucoma [2]. Cataract is one of the major causes of legal blindness in patients with diabetes, as previously reported in the Wisconsin Epidemiological Study of Diabetic Retinopathy [3, 4]. Previous literature on human diabetic cataract has reported elevated glucose concentration [5] and subsequent increase in the levels of sorbitol and fructose [5, 6], both of which are generated through glucose metabolism in the polyol pathway. A previous study has reported that the levels of reduced glutathione (GSH), an antioxidant peptide, were observed to be lower in human diabetic cataract than in cataract in age-matched, nondiabetic individuals [8].
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