Animal Models in Cataract Research

Cataract is the leading cause of blindness worldwide and accounts for approximately half of all forms of vision loss. Currently, the only way to treat cataracts is by surgery. However, with an aging population and the increasing prevalence of diabetes, the demand for cataract surgery and the need for cost-effective solutions are growing. To reduce the need for cataract surgery, alternative medical therapies to delay cataracts are required. However, given the difficulty in accessing intact human cataractous lenses, due to new cataract procedures that result in phacoemulsification of the lenses, understanding the pathogenesis of this disease and testing the efficacy of potential therapies in humans is problematic. Therefore, researchers have tried to create suitable animal models of cataract to identify therapeutic options. Here we provide an overview of the two most common types of cataract: age-related nuclear cataract and diabetic cataract, with a specific focus on diabetic cataract and diabetic cataract animal models. Early studies using diabetic animal models provided us with extensive knowledge of the polyol pathway and the role of aldose reductase and sorbitol accumulation in the initiation of osmotic stress. However, the inability of aldose reductase inhibitors to ameliorate cataracts in humans, as it did in rats, highlights the importance of selecting appropriate animal models that mimic the human condition. To facilitate the researcher with this, we describe key changes to the diabetic cataractous lens in terms of lens physiology, cellular structure, and biochemistry. Using this set of human lens parameters, we then assess existing animal cataract models and their suitability for mimicking the processes associated with the development of diabetic cataract in humans and for testing of potential therapeutic interventions that are can be translated and effective in humans.