The prevention of cataract caused by oxidative stress in cultured rat lenses. II. Early effects of photochemical stress and recovery.
Previous work has demonstrated that photochemically induced oxidative stress generated with 4 microM riboflavin in a 4% oxygen atmosphere utilizing daylight type radiation is capable of causing cataract in cultured rat lenses. Such cataract is prevented by the GSH peroxidase type mimic, AL-3823A. Examination of the early stages of cataract formation produced by short-term oxidative stress and recovery is now reported. A 24-hr oxidative stress, under the above conditions, causes loss of transparency, particularly in the equatorial region, increased hydration, loss of glyceraldehyde-3-PO4 dehydrogenase activity, oxidation of non-protein thiol and a decrease in 86Rb and [14C]choline uptake and ATP levels. Examination of recovery of these parameters during a 72-hr period indicates, in most cases, little or no reversal of oxidative damage. Hydration and loss of non-protein thiol continued during the recovery period. The presence of AL-3823A during the stress period prevented change in all parameters. Transport systems appear to be particularly vulnerable to this type of oxidative stress losing 50% or more activity within 4 hr. Even after a 2-hr stress, choline transport did not recover even though, under these conditions, ATP levels had only decreased slightly. Cytosolic components such as non-protein thiol and glyceraldehyde-3-PO4 dehydrogenase also showed little change after a 4-hr insult. 86Rb efflux experiments indicated no change in permeability during a 24-hr stress period. The overall conclusion from these studies is that a 24-hr oxidative stress which appears to reflect physiological conditions existing during cataract development, causes extensive, irreversible damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Spector
A
A
Department of Ophthalmology, College of Physicians & Surgeons of Columbia University, New York, NY 10032.
Wang
G M
GM
Wang
R R
RR
D000818:Animals; D002386:Cataract / Q000209:etiology* / Q000378:metabolism; D046508:Culture Techniques; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D008027:Light; D009942:Organometallic Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012256:Riboflavin; D013312:Stress, Physiological / Q000150:complications*; D013438:Sulfhydryl Compounds / Q000378:metabolism
C080254:AL 3823A; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012256:Riboflavin