Diabetes is a metabolic disease resulting from the body's insufficient production or use of insulin, a peptide hormone responsible for regulating glucose levels in the blood and tissues. Especially when improperly managed, diabetes results in a number of complications over time, affecting nearly every organ system, including the ocular tissue. In addition to increased risk for glaucoma and cataracts, the most threatening ocular implication of diabetes is diabetic retinopathy, an aggressive disorder historically clinically associated with a variety of retinal microvascular abnormalities. Disease severity is typically classified into two types: nonproliferative diabetic retinopathy (NPDR), marked by microaneurysms, intraretinal hemorrhaging, and other microvascular aberrations, and proliferative diabetic retinopathy (PDR), characterized by the onset of neovascularization and vitreal hemorrhaging.1 Diabetic macular edema (DME), another manifestation of diabetic retinopathy involving macular thickening due to fluid accumulation, is accountable for a great proportion of diabetes-related vision loss. 2 While advanced stages of PDR have classically been regarded as the most threatening to sight, visual dysfunction at all stages, even those deemed mild by clinical evaluation, is now apparent. As the leading cause of blindness in US working-age adults, 3 diabetic retinopathy has many economic implications for healthcare systems and the overall population, 4 as well as a variety of personal consequences on patient quality of life. 5,6 However, if addressed early and proactively, the incidence of severe vision loss from diabetic retinopathy can be significantly reduced. This review will discuss the systemic measures necessary for diabetic retinopathy prevention, as well as interventions currently available to delay or stop retinopathy progression once diagnosed. The limitations of present treatment options will also be addressed, as well as current developments in the search for new endpoints and technologies that may allow for earlier detection.Finally, investigations of some of the new therapies and future approaches to diabetic retinopathy research will be reviewed. Systemic Control and Preventive InterventionAs the prevalence of diabetes worldwide continuously increases, incidence of vision-threatening diabetic retinopathy is projected to nearly triple in the next 40 years. 7 For patients diagnosed with diabetes, the most important method of preventing visual complications, such as retinopathy, is to control the diabetes at a systemic level. Tight regulation of glycemia via intensive insulin therapy significantly reduces the risk for retinopathy prevalence and progression. 8 In addition to its effect on glycemic and circulating insulin levels, systemic insulin therapy has been shown to have a local impact on ocular tissue as well, including restoration of retinal insulin receptor signaling cascade and rod photoreceptor function. 9,10We recently demonstrated that both components of systemic insulin treatment-normaliza...

Diabetic retinopathy is the leading cause of vision loss in working-age individuals in the United States and is expected to continue growing with the increased prevalence of diabetes. Streptozotocin-induced hyperglycemia in rats is the most commonly used model for diabetic retinopathy. Previous studies have shown that this model can lead to different inflammatory changes in the retina depending on the strain of rat. Our previous work has shown that crystallin proteins, including members of the alpha- and beta/gamma-crystallin subfamilies, are upregulated in the STZ rat retina. Crystallin proteins have been implicated in a number of cellular processes, such as neuroprotection, non-native protein folding and vascular remodeling. In this current study, we have demonstrated that unlike other strain-dependent changes, such as inflammatory cytokines and growth factor levels, in the STZ rat, the protein upregulation of crystallins is consistent across the Brown Norway, Long-Evans and Sprague-Dawley rat strains in the context of diabetes. Taken together, these data illustrate the potential critical role played by crystallins, and especially alpha-crystallins, in the retina in the context of diabetes.