ABSTRACT This review exanulies the hypothesis that oxidative stress is an initiating factor for the development of maturity onset cataract and describes the events leading to lens opacification. Data are reviewed that indicate that extensive oxidation of lens protein and lipid is associated with human cataract found in older individuals whereas littleoxidation (and only in membrane components) is found in control subjects of similar age. A signfficantproportion of lenses and aqueous humor taken from cataract patients have elevated H202 levels. Because 11202, at concentrations found in cataract, can cause lens opacification and produces a pattern of oxidation similar to that found in cataract, itis concluded that H202 is the major oxidant involved in cataract formation. This viewpoint is further supported by experiments showing that cataract formation in organ culture caused by photochemically generated superoxide radical, H202, and hydroxyl radical is completely prevented by the addition of a GSH peroxidase nmrnc. The damage caused by oxidative stress does not appear to be reversible and there is an inverse relationship between the stress period and the time required for loss of transparency and degeneration of biochemical parameters such as ATP, GPD, nonprotein thiol, and hydration. After exposure to oxidative stress, the redox set point of the single layer of the lens epitheial cells (but not the remainder of the lens) quickly changes, going from a strongly reducing to an oxidizing environment. Almost concurrent with this change is extensive damage to DNA and membrane pump systems, followed by loss of epithelial cell viabifity and death by necrotic and apoptotic mechanisms. The data suggest that the epithelialcelllayer is the initialsiteof attack by oxidative stressand that involvement of the lens fibers follows, leading to cortical cataract.-Spector, A. Oxidative stress-induce
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