Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span. As the global aging population is expanding, it is imperative to uncover strategies to increase health span and reduce the economic burden of this age-related disease. While there are some treatments available for age-related vision loss, such as surgical removal of cataracts, many causes of vision loss, such as dry age-related macular degeneration (AMD), remain poorly understood and no treatments are currently available. Therefore, it is necessary to better understand the factors that contribute to disease progression for age-related vision loss and to uncover methods for disease prevention. One such factor is the effect of diet on ocular diseases. There are many reviews regarding micronutrients and their effect on eye health. Here, we discuss the impact of dietary patterns on the incidence and progression of age-related eye diseases, namely AMD, cataracts, diabetic retinopathy, and glaucoma. Then, we focus on the specific role of dietary carbohydrates, first by outlining the physiological effects of carbohydrates on the body and then how these changes translate into eye and age-related ocular diseases. Finally, we discuss future directions of nutrition research as it relates to aging and vision loss, with a discussion of caloric restriction, intermittent fasting, drug interventions, and emerging randomized clinical trials. This is a rich field with the capacity to improve life quality for millions of people so they may live with clear vision for longer and avoid the high cost of vision-saving surgeries.

Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.

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The glyoxalase system is critical for the detoxification of advanced glycation end-products (AGEs). AGEs are toxic compounds resulting from the non-enzymatic modification of biomolecules by sugars or their metabolites through a process called glycation. AGEs have adverse effects on many tissues, playing a pathogenic role in the progression of molecular and cellular aging. Due to the age-related decline in different anti-AGE mechanisms, including detoxifying mechanisms and proteolytic capacities, glycated biomolecules are accumulated during normal aging in our body in a tissue-dependent manner. Viewed in this way, anti-AGE detoxifying systems are proposed as therapeutic targets to fight pathological dysfunction associated with AGE accumulation and cytotoxicity. Here, we summarize the current state of knowledge related to the protective mechanisms against glycative stress, with a special emphasis on the glyoxalase system as the primary mechanism for detoxifying the reactive intermediates of glycation. This review focuses on glyoxalase 1 (GLO1), the first enzyme of the glyoxalase system, and the rate-limiting enzyme of this catalytic process. Although GLO1 is ubiquitously expressed, protein levels and activities are regulated in a tissue-dependent manner. We provide a comparative analysis of GLO1 protein in different tissues. Our findings indicate a role for the glyoxalase system in homeostasis in the eye retina, a highly oxygenated tissue with rapid protein turnover. We also describe modulation of the glyoxalase system as a therapeutic target to delay the development of age-related diseases and summarize the literature that describes the current knowledge about nutritional compounds with properties to modulate the glyoxalase system.

Purpose Age-related cataracts affect the majority of older adults and are a leading cause of blindness worldwide. Treatments that delay cataract onset or severity have the potential to delay cataract surgery, but require relevant animal models that recapitulate the major types of cataracts for their development. Unfortunately, few such models are available. Here, we report the lens phenotypes of aged mice lacking the critical antioxidant transcription factor Nfe2l2 (designated as Nrf2 −/−). Methods Three independent cohorts of Nrf2 −/− and wild-type C57BL/6J mice were evaluated for cataracts using combinations of slit lamp imaging, photography of freshly dissected lenses, and histology. Mice were fed high glycemic diets, low glycemic diets, regular chow ad libitum, or regular chow with 30% caloric restriction. Results Nrf2 −/− mice developed significant opacities between 11 and 15 months and developed advanced cortical, posterior subcapsular, anterior subcapsular, and nuclear cataracts. Cataracts occurred similarly in male mice fed high or low glycemic diets, and were also observed in 21-month male and female Nrf2 −/− mice fed ad libitum or 30% caloric restriction. Histological observation of 18-month cataractous lenses revealed significant disruption to fiber cell architecture and the retention of nuclei throughout the cortical region of the lens. However, fiber cell denucleation and initiation of lens differentiation was normal at birth, with the first abnormalities observed at 3 months. Conclusions Nrf2 −/− mice offer a tool to understand how defective antioxidant signaling causes multiple forms of cataract and may be useful for screening drugs to prevent or delay cataractogenesis in susceptible adults.