NUCLEAR LIGHT-SCATTERING, DISULFIDE FORMATION AND MEMBRANE DAMAGE IN LENSES OF OLDER GUINEA-PIGS TREATED WITH HYPERBARIC-OXYGEN

Nuclear cataract, a major cause of loss of lens transparency in the ag ing human, has long been thought to be associated with oxidative damag e, particularly at the site of the nuclear plasma membrane. However, f ew animal models have been available to study the mechanism of the opa city. Hyperbaric oxygen (HBO) has been shown to produce increased nucl ear light scattering (NLS) and nuclear cataract in lenses of mice and human patients, In the present study, older guinea pigs (Initially 17- 18 months of age) were treated with 2.5 atmospheres of 100% O-2 for 2- 2.5-hr periods, three times per week, for up to 100 times. Examination by slit-lamp biomicroscopy showed that exposure to HBO led to increas ed NLS in the lenses of the animals after as few as 19 treatments, com pared to lenses of age-matched untreated and hyperbaric air-treated co ntrols. The degree of NLS and enlargement of the lens nucleus continue d to increase until 65 O-2-treatments, and then remained constant unti l the end of the study. Exposure to O-2 for 25 instead of 2 hr acceler ated the increase in NLS; however, distinct nuclear cataract was not o bserved in the animals during the period of investigation. A number of morphological changes in the experimental lens nuclei, as analysed by transmission electron microscopy, were similar to those recently repo rted for human immature nuclear cataracts (Costello, Oliver and Cobo, 1992). O-2-induced damage to membranes probably acted as scattering ce nters and caused the observed increased NLS. A general state of oxidat ive stress existed in the lens nucleus of the O-2-treated animals, pri or to the first appearance of increased NLS, as evidenced by increased levels of protein-thiol mixed disulfides and protein disulfide. The l evels of mixed disulfides in the experimental nucleus were remarkably high, nearly equal to the normal level of nuclear GSH. The level of GS H in the normal guinea pig lens decreased with age in the nucleus but not in the cortex; at 30 months of age the nuclear lever of GSH was on ly 4% of the cortical value. HBO-induced changes in the lens nucleus i ncluded loss of soluble protein, increase in urea-insoluble protein an d slight decreases in levels of GSH and ascorbate; however, there was no accumulation of oxidized glutathione. Intermolecular protein disulf ide in the experimental nucleus consisted mainly of gamma-crystallin, but crosslinked alpha-, beta- and xi-crystallins were also present. Th e results support the hypothesis that oxidation, especially at the sit e of the lens nuclear membrane, is a primary cause of senile nuclear c ataract. Molecular oxygen is implicated in the etiology of this type o f cataract. HBO may be a useful experimental model for studying the me chanism of the disease.