Oxygen free radicals are produced continuously in all aerobic biological systems. These can function as intermediates in normal metabolish but may play a detrimental role in the mediation of cellular damage and age related degeneration. Superoxide dismutase (SOD) and oxygen scavenging enzymes have evolved to protect biological systems utilizing oxygen from such damage. Age related changes in ocular tissue in which oxygen radicals are presumed to play a role include the disease glaucoma, cataract formation, and vitreous degeneration. Elevated oxygen levels are the primary identifiable event in newborns predisposing to the disease retrolental fibroplasia. This work will investigate the sources in ocular tissue of superoxide and other free radicals, the levels of protective enzymes, and will attempt to identify exogenous pharmaceutical agents which may prevent the damage caused by oxygen intermediates. Investigations planned include the study of a model for retrolental fibroplasia in cats, and a system for investigating vitreous liquefaction induced by reactive oxygen intermediates. These systems will be studied in vitro by the introduction of generators of oxygen radicals with correlation of observed biochemical and pathologic changes in comparison with the in vivo addition of oxygen radical scavengers to the same models. Also studied will be human cataracts in comparison with normal lenses. Levels of SOD present in eyes will be studied as a function of age. While previous work has focused upon the biochemistry of copper-zinc SOD, investigations are also planned of the biochemistry and role of the mitochondrial manganese SOD.
