<ul>
 <li>
 Reactive oxygen intermediates (ROIs): collective term for free radicals, hydrogen peroxide and
 singlet oxygen
 </li>
 <li>
 Free radicals: molecules or atoms that possess an unpaired electron making them highly reactive.
 Examples
 </li>
 <ul>
 <li>Superoxide anion</li>
 <li>Hydroxyl radical: extremely reactive</li>
 <li>Lipid peroxyl radicals</li>
 </ul>
 <li>Normal oxygen metabolism via cytochrome oxidase in mitochondria yields water</li>
</ul>
<ul>
 <li>Sources of ROIs</li>
 <ul>
 <li>
 A small percentage of oxygen undergoes reduction creating ROIs: superoxide, hydrogen peroxide,
 water and the hydroxyl radical
 </li>
 <ul>
 <li>These can leak out and damage other tissue components</li>
 <li>They can be neutralised by detoxifying enzymes</li>
 </ul>
 <li>Enzymatic synthesis of eicosanoids can also produce ROIs</li>
 <li>Ionizing radiation</li>
 <li>Metabolism of certain chemicals and drugs</li>
 <li>Inflammation and infection</li>
 </ul>
 <li>Detoxifying enzymes</li>
 <ul>
 <li>
 Superoxide dismutase: converts superoxide radical (O2-) to hydrogen peroxide and oxygen
 without oxidizing other molecules
 </li>
 <li>
 Catalase and peroxidase: reduce hydrogen peroxide to water without forming the toxic hydroxyl
 radical
 </li>
 <ul>
 <li>Catalase produces water and oxygen from hydrogen peroxide</li>
 <li>Peroxidases produce water and oxidised substrate</li>
 </ul>
 </ul>
</ul>

## Oxidative damage to the lens
<ul>
 <li>Lens is vulnerable due to lower levels of oxygen and trace amounts of transition metals</li>
 <li>Metal-catalysed auto-oxidation can lead to damaging oxidants</li>
 <ul>
 <li>Oxidised glutathione</li>
 <li>Dehydroascorbic acid</li>
 <li>Hydrogen peroxide and hydroxyl radicals</li>
 </ul>
 <li>UV light can generate ROIs</li>
 <li>
 Repair mechanisms are present in the epithelium but not in the cortex or nucleus so damage there
 is permanent
 </li>
 <ul>
 <li>Damage to lens proteins leads to cross-linking and cataract</li>
 </ul>
</ul>
<HotTopic>
 Antioxidant systems in young lenses
 <ul>
 <li>
 Glutathione peroxidase (most important)
 </li>
 <li>Catalase</li>
 <li>
 Superoxide dismutase
 </li>
 <li>Scavengers: glutathione, ascorbic acid, vitamin E, carotenoids</li>
 </ul>
</HotTopic>

## Retinal damage by free radicals
<ul>
 <li>Photoreceptors degenerate when exposed to free radicals such as</li>
 <ul>
 <li>Hyperbaric oxygen</li>
 <li>Iron overload</li>
 <li>Lipid peroxidases within the vitreous</li>
 </ul>
 <li>Vulnerabilities</li>
 <ul>
 <li>
 Rod outer segments have high polyunsaturated fat content which are sensitive to peroxidation
 </li>
 <li>Rod inner segments are rich in mitochondria which can leak ROIs</li>
 <li>Highly vascularised choroid and retina increase the risk of oxidative damage</li>
 <li>Light exposure triggers photo-oxidation</li>
 </ul>
</ul>
<ul>
 <li>RPE is rich in antioxidant enzymes</li>
 <ul>
 <li>Melanin: functions as a light trap</li>
 <li>Sensitive to dietary antioxidant deficiency</li>
 <li>Selenium: an antioxidant, needed for the action of glutathione peroxidase</li>
 <li>Vitamin E: scavenges free radicals and interrupts the auto-oxidation reaction</li>
 </ul>
 <li>
 Carotenoids (xanthophylls) act as a blue light filter, shielding the retina from this radiation
 </li>
 <ul>
 <li>Beta-carotene: precursor of vitamin A. Free radical trap but not much in eye</li>
 <li>Lutein: dispersed throughout retina</li>
 <li>Zeaxanthin: concentrated at fovea</li>
 <li>NB: carotenoids are not present in the RPE</li>
 </ul>
 <li>Superoxide dismutase</li>
 <li>Catalase&nbsp;</li>
 <li>Ascorbate (vitamin C): synergistic with vitamin E to scavenge free radicals</li>
</ul>

Pathology

Free Radicals And Antioxidants

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

Lacrimal Glands

Tear Film

Eyelids

Blinking

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Cornea

Corneal Structure And Development

Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

Lens

Posterior segment

Choroid

Vitreous

Retinal Macrostructure

Neurosensory Retina

Retinal Pigment Epithelium

Neuroanatomy

Venous Sinuses

Cerebral Ventricles

Cerebral Blood Supply

Supranuclear Gaze Pathways

Head And Neck Autonomic Nervous Supply

Head And Neck Glands

Osteology

Nerves

Muscles And Pharyngeal Arches

Extraocular Nerves

Sensory Nerves

Physiology

Physics Of Blood Flow

Neuronal Control Of Blood Vessels

Oxygen-Haemoglobin Dissociation Curve

Cytochrome p450

Pituitary Gland

Thyroid Hormone Production

Insulin

Glucagon

Parathyroid Hormone

Corticosteroids

Catecholamines

Cardiac Cycle

Renal Physiology

Fluid Balance

Acid-Base Balance

Muscle Physiology

Sensory Fibres

Cutaneous Receptors

Endocytosis

Glycosaminoglycans

Condensed Ocular Biochemistry

Eye Movements

Accomodation

Vision

Visual Cycle And Phototransuction

Visual Pathway

Visual Acuity

Colour Vision

Binocular Vision

Collagen

Tissue Damage

Inflammation

Disease Entities

Wound Healing

Thrombosis / Atherosclerosis

Cell Growth

Neoplasia

Histopathology

Nystagmus

Immunology

Ocular Immunology

Microbiology

Viral Infections

Bacterial Infections

Fungal Infections

Protozoa

Nematodes

Antimicrobials

Genetics

Chromosomes

Mitosis

Meiosis

Genes

Polypeptide Synthesis

Histones

MicroRNA

Hardy-Weinberg Equilibrium

Mutations

Chromosome Defects

Autosomal Inheritance

X-Linked Inheritance

Mitochondrial Inheritance

Multifactorial Inheritance