Diabetic retinopathy is the leading cause of blindness worldwide in adults aged 20 to 64 years. Several metabolic pathways, initiated by hyperglycemia and lack of insulin signaling, generate oxidative stress and are implicated in the development of diabetic retinopathy:
Advanced glycation end products (AGEs) result from nonenzymatic glycation of various molecules (proteins, lipids, nucleic acids) and exist in foods prepared at very high temperatures. AGEs interact with specific cell surface receptors, which then signal intracellular inflammatory pathways, leading to generation of ROS.
ROS can lead to long-term changes via epigenetic modification, especially in mitochondrial DNA. This may partly explain the phenomenon of metabolic memory, wherein beneficial effects of past tight metabolic control persist for a period, reducing the progression of retinopathy, as demonstrated by the Diabetes Control and Complications Trial (DCCT). Conversely, in patients with poor metabolic control, epigenetic modifications may allow diabetic retinopathy to progress even after intensive control has been achieved. Most data supporting a role for antioxidants in diabetic retinopathy have come from cell culture or animal models. One clinical trial evaluated the role of the PKC inhibitor ruboxistaurin, which reduced vision loss and the need for macular laser therapy in comparison to controls in patients with diabetic retinopathy.
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Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.