OT-674 suppresses photooxidative processes initiated by an RPE lipofuscin fluorophore.
The pathological processes involved in age-related macular degeneration (AMD) include retinal pigment epithelial (RPE) cell degeneration; oxidative mechanisms likely contribute to the demise of these cells. Indeed, RPE cells may be particularly susceptible to photooxidative mechanisms since they accumulate retinoid-derived photoreactive compounds that constitute the lipofuscin of the cell. Thus we undertook to test the capacity of OT-674, the reduction product (Tempol-H) of the nitroxide Tempol, to suppress photooxidative processes initiated by the RPE lipofuscin fluorophore A2E. Accordingly, when ARPE-19 cells that had accumulated A2E were irradiated at 430 nm, pretreatment with OT-674 (0.01-10 mM) was found to confer a resistance to cell death. Monitoring by quantitative HPLC also showed that OT-674 reduced A2E photooxidation in a cell-free system. Moreover, when presented with a singlet oxygen generator, OT-674 served as a quencher of singlet oxygen that was more effective than Trolox and alpha-tocopherol. We conclude that OT-674 is a potent antioxidant that suppresses photooxidative processes generated in cultured RPE cells by the lipofuscin fluorophore A2E. As oxidative damage to RPE cells is considered to be a risk factor for AMD, antioxidant therapy with OT-674 may serve a protective role.
Zhou
Jilin
J
Department of Ophthalmology, Columbia University, New York, NY, USA.
Jang
Young P
YP
Chang
Stanley
S
Sparrow
Janet R
JR
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002474:Cell-Free System; D003116:Color; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D019811:Hydroxylamine; D008027:Light; D008062:Lipofuscin / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010777:Photochemistry; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D026082:Singlet Oxygen / Q000378:metabolism
D003497:Cyclic N-Oxides; D005456:Fluorescent Dyes; D008062:Lipofuscin; D026082:Singlet Oxygen; D019811:Hydroxylamine; C505333:TEMPOL-H