Tempol-H inhibits opacification of lenses in organ culture.
Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a lens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H(2)O(2) or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H(2)O(2)-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate (3)H-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract.
Zigler
J Samuel
JS
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, Bethesda, MD, USA. ziglers@nei.nih.gov
Qin
Chuan
C
Kamiya
Toshikazu
T
Krishna
Murali C
MC
Cheng
Qiufang
Q
Tumminia
Santa
S
Russell
Paul
P
D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D002417:Cattle; D002794:Choline / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009924:Organ Culture Techniques; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D014994:Xylose / Q000633:toxicity
D003497:Cyclic N-Oxides; D016877:Oxidants; D013113:Spin Labels; D014994:Xylose; D006861:Hydrogen Peroxide; D005978:Glutathione; D002794:Choline; C001803:tempol