H2O2 stress is shown to produce
cataract in cultured rat
lenses. The loss of transparency begins in the equatorial region within 24 hours and the entire superficial cortex is opaque by 96 hours. No involvement of the nuclear region is observed. However after an additional 48 hours, the nuclear region becomes opaque. The loss of transparency is accompanied by a large uptake of H2O which occurs gradually over the 96 hour period, complete loss of
glyceraldehyde phosphate dehydrogenase (GPD) activity, almost complete loss of non-
protein thiol and a slight decrease in
protein thiol. Control
lenses show no change other than the establishment of a new non-
protein thiol base line approximately 60% lower than 0 time levels. The Alcon
glutathione peroxidase type mimic,
AL-3823A, completely eliminates almost all of the H2O2 induced effects and the lens remains transparent. Utilizing a more severe photochemical model than may be anticipated physiologically with 10 microM
riboflavin and exposure to daylight fluorescent lamps, significant concentrations of
superoxide and low levels of
OH. are produced as well as extraordinarily high concentrations of H2O2 ranging from about 400 to 1000 microM. As with the H2O2 model, opacification begins at the equator but the
cataract develops more rapidly, the lens being completely opaque by 68 hours. Hydration, GPD activity, non-
protein and
protein thiol all decrease more rapidly than in the H2O2 model.
AL-3823A prevents loss of transparency until approximately 92 hours and markedly decreases changes in other parameters. At 92 hours, slight loss of transparency is observed.
Catalase is somewhat less effective.
AL-3823A is shown to also significantly decrease
superoxide levels. The marked delay in the onset of changes in lens biochemistry and physiology in the severe photochemical stress model and the maintenance of normal parameters in the H2O2 model in the presence of
AL-3823A suggests that such compounds may prevent
cataract caused by oxidative stress under physiological conditions.