Oxidative stress, mitochondrial damage and diabetic retinopathy

• In diabetes, reactive oxygen species are elevated in the retina and metabolism is impaired.
• ROS damage the mitochondrial function and DNA, compromising the electron transport system.
• Genes important in regulation of ROS are epigenetically modified, increasing ROS accumulation.
• Antioxidants target multiple steps of oxidative stress and mitochondrial damage.
• Antioxidants ameliorate retinopathy in diabetic rats, warranting controlled clinical trials.

Diabetes has emerged as an epidemic of the 21st century, and retinopathy remains the leading cause of blindness in young adults and the mechanism of this blinding disease remains evasive. Diabetes-induced metabolic abnormalities have been identified, but a causal relationship between any specific abnormality and the development of this multi-factorial disease is unclear. Reactive oxygen species (ROS) are increased and the antioxidant defense system is compromised. Increased ROS result in retinal metabolic abnormalities, and these metabolic abnormalities can also produce ROS. Sustained exposure to ROS damages the mitochondria and compromises the electron transport system (ETC), and, ultimately, the mitochondrial DNA (mtDNA) is damaged. Damaged mtDNA impairs its transcription, and the vicious cycle of ROS continues to propagate. Many genes important in generation and neutralization of ROS are also epigenetically modified further increasing ROS, and the futile cycle continues to fuel in. Antioxidants have generated beneficial effects in ameliorating retinopathy in diabetic rodents, but limited clinical studies have not been encouraging. With the ongoing use of antioxidants for other chronic diseases, there is a need for a controlled trial to recognize their potential in ameliorating the development of this devastating disease.