The prevention of cataract caused by oxidative stress in cultured rat lenses. I. H2O2 and photochemically induced cataract.
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.
Spector
A
A
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Wang
G M
GM
Wang
R R
RR
Garner
W H
WH
Moll
H
H
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002386:Cataract / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006861:Hydrogen Peroxide; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D009924:Organ Culture Techniques; D009929:Organ Size; D009942:Organometallic Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012256:Riboflavin; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
C080254:AL 3823A; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D013481:Superoxides; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012256:Riboflavin