Sources of Reactive Oxygen Species
Reactive oxygen species are generated from metabolic processes, inflammatory responses, and exposure to UV light. ROS include hydrogen peroxide (H2O2) and singlet oxygen (1O2), as well as lipid peroxides and reactive carbohydrates such as ketoamine and ketoaldehyde groups. Free radicals, another group of ROS, possess an unpaired electron that makes them highly reactive toward other molecular species.
Exogenous sources of ROS include UV light and tobacco smoke. Endogenous sources include the electron transport chain in mitochondria and, as part of our innate immune response by neutrophils and macrophages, respiratory burst, where superoxide anion (O2•−) and the hydroxyl radical (OH•) form to attack pathogens (Fig 14-1). The nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) constitute an enzyme family that functions primarily to produce ROS and is expressed in many cells. Table 14-1 presents some important ROS.
Toxicity from ROS leads to cell death. ROS may directly induce DNA damage, resulting in cell death via apoptosis. Cell death can also occur through loss of the barrier function of the plasma membrane via a process known as lipid peroxidation. Structures with a high concentration of polyunsaturated fatty acids (PUFAs) are particularly susceptible to lipid peroxidation.
Figure 14-1 Generation and detoxification of reactive oxygen species. Left, Generation of hydroxyl radicals (OH•) through the reaction of iron with the superoxide anion (O2•−) and hydrogen peroxide (H2O2). Center, Conversion of O2•− into H2O2 and the 3 subsequent pathways involved in eliminating it via (1) glutathione peroxidase; (2) catalase; and (3) peroxidase. Right, The role of the glucose-initiated pentose phosphate pathway in providing reduced glutathione (GSH) for redox reactions. GSSG = oxidized glutathione; NADP+ = nicotinamide adenine dinucleotide phosphate; NADPH = reduced NADP+.
(Modified with permission from Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E.
The Eye: Basic Sciences in Practice.
4th ed. St Louis: Saunders; 2016:194.)
Table 14-1 ROS and Antioxidant Pathways
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.