Free Radicals And Antioxidants

• Reactive oxygen intermediates (ROIs): collective term for free radicals, hydrogen peroxide and singlet oxygen

• Free radicals: molecules or atoms that possess an unpaired electron making them highly reactive. Examples

• Superoxide anion
• Hydroxyl radical: extremely reactive
• Lipid peroxyl radicals
• Normal oxygen metabolism via cytochrome oxidase in mitochondria yields water

• Sources of ROIs

• A small percentage of oxygen undergoes reduction creating ROIs: superoxide, hydrogen peroxide, water and the hydroxyl radical

• These can leak out and damage other tissue components
• They can be neutralised by detoxifying enzymes
• Enzymatic synthesis of eicosanoids can also produce ROIs
• Ionizing radiation
• Metabolism of certain chemicals and drugs
• Inflammation and infection
• Detoxifying enzymes

• Superoxide dismutase: converts superoxide radical (O2-) to hydrogen peroxide and oxygen without oxidizing other molecules

• Catalase and peroxidase: reduce hydrogen peroxide to water without forming the toxic hydroxyl radical

• Catalase produces water and oxygen from hydrogen peroxide
• Peroxidases produce water and oxidised substrate

Oxidative damage to the lens

• Lens is vulnerable due to lower levels of oxygen and trace amounts of transition metals
• Metal-catalysed auto-oxidation can lead to damaging oxidants
• Oxidised glutathione
• Dehydroascorbic acid
• Hydrogen peroxide and hydroxyl radicals
• UV light can generate ROIs

• Repair mechanisms are present in the epithelium but not in the cortex or nucleus so damage there is permanent

• Damage to lens proteins leads to cross-linking and cataract

Retinal damage by free radicals

• Photoreceptors degenerate when exposed to free radicals such as
• Hyperbaric oxygen
• Iron overload
• Lipid peroxidases within the vitreous
• Vulnerabilities

• Rod outer segments have high polyunsaturated fat content which are sensitive to peroxidation

• Rod inner segments are rich in mitochondria which can leak ROIs
• Highly vascularised choroid and retina increase the risk of oxidative damage
• Light exposure triggers photo-oxidation

• RPE is rich in antioxidant enzymes
• Melanin: functions as a light trap
• Sensitive to dietary antioxidant deficiency
• Selenium: an antioxidant, needed for the action of glutathione peroxidase
• Vitamin E: scavenges free radicals and interrupts the auto-oxidation reaction

• Carotenoids (xanthophylls) act as a blue light filter, shielding the retina from this radiation

• Beta-carotene: precursor of vitamin A. Free radical trap but not much in eye
• Lutein: dispersed throughout retina
• Zeaxanthin: concentrated at fovea
• NB: carotenoids are not present in the RPE
• Superoxide dismutase
• Catalase 
• Ascorbate (vitamin C): synergistic with vitamin E to scavenge free radicals