Reactive Oxygen Species and Defense Mechanisms
Although the eye is constantly exposed to light, it is protected from the consequences of UV-light exposure via various mechanisms employed by different ocular structures. The cornea and the lens prevent different wavelengths of UV light from reaching the retina (see Chapter 10, Fig 10-3). The high concentration of ascorbate (vitamin C) in the aqueous and vitreous also acts to block UV light and participates in cellular antioxidant pathways.
Cellular components are protected from ROS by antioxidant mechanisms. Cells contain enzymes that neutralize ROS and the toxic metabolites formed by the interaction between ROS and cellular components (see Fig 14-1). These enzymes include superoxide dismutase (SOD), catalase, glutathione reductase, and glutathione peroxidase (GSH-Px); they are discussed later in the chapter. The transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) regulates expression of numerous antioxidant genes and is upregulated under oxidative stress. Nrf2 is a potential therapeutic target, and induction of Nrf2 enhanced RGC survival in experimental models of oxidative stress generated by ischemia–reperfusion injury.
The cell is also protected from ROS by compartmentalizing these species, preventing their contact with intracellular components. An example of this is the electron transport chain, which is contained within the walls of the mitochondria. However, some reactive species may leak out of their enzyme-binding sites or escape antioxidant enzymes, causing damage to cellular components such as proteins, membrane lipids, and DNA. In addition, any free iron (Fe2+) present may catalyze formation of OH• from superoxide and H2O2 (see Fig 14-1).
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.