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OT‐674 Suppresses Photooxidative Processes Initiated by an RPE Lipofuscin Fluorophore
Author(s) -
Zhou Jilin,
Jang Young P.,
Chang Stanley,
Sparrow Janet R.
Publication year - 2007
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2007.00205.x
Subject(s) - lipofuscin , trolox , chemistry , singlet oxygen , microbiology and biotechnology , reactive oxygen species , programmed cell death , cell , cell damage , oxidative phosphorylation , antioxidant , biochemistry , apoptosis , biology , oxygen , organic chemistry , dpph
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 m m ) 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 α‐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.