Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic.
Oxidative stress is known to cause cataracts in lens culture systems and is believed to be an important factor contributing to human cataracts. In this communication, it is demonstrated that cataract development of cultured rat lenses produced as a result of photochemically induced oxidation in a 4% oxygen atmosphere similar to the native environment of the lens can be blocked by the transition metal complex AL-3823A. In this system, riboflavin is added to the medium as a photosensitizer. AL-3823A acts primarily as a glutathione peroxidase mimic, which catalytically metabolizes H2O2 and also has low superoxide dismutase-like activity. Measurements of H2O2, O2.-, and OH. indicate that appreciable levels of the first two of these oxidants and low levels of OH. are produced by this photochemical stressing system. The H2O2 concentrations are similar to those found in some patients with cataracts. The development of cataracts was followed over a 96-hr period. Transparency, hydration, glyceraldehyde-3-phosphate dehydrogenase activity, and protein and nonprotein thiol were monitored. All parameters show marked changes during the 96-hr period. However, in the presence of 200 microM AL-3823A, no difference between control and light-exposed lenses was observed with respect to these parameters. The results suggest that in vivo human cataract development caused by oxidative stress may be prevented by compounds of this type.
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 / Q000139:chemically induced / Q000517:prevention & control*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D009942:Organometallic Compounds / Q000494:pharmacology*; D010100:Oxygen / Q000633:toxicity; D010777:Photochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012256:Riboflavin / Q000494:pharmacology*
C080254:AL 3823A; D009942:Organometallic Compounds; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D010100:Oxygen; D012256:Riboflavin