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J. Zhou, J.R. Sparrow, Y.P. Jang, S. Chang; OT–674 Protects Against Photooxidative Processes in RPE Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2071.
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The pathogenesis of AMD involves RPE cell degeneration and much consideration has been given to the role of oxidative damage in the demise of these cells. Consequently, there is also considerable interest in forms of therapy involving antioxidants. As cells that are exposed to light, RPE may be at risk, at least in part, because they accumulate photoreactive compounds that constitute the lipofuscin of the cell. Here we have examined the antioxidant capacity of the hydroxylamine reduction product (Tempol–H) of the nitroxide Tempol (OT–674). OT–674 was tested in an RPE cell culture system that allows us to evaluate light–initiated damage to RPE cells that have accumulated the RPE lipofuscin fluorophore A2E.
Human adult RPE (ARPE–19) accumulated A2E in culture, were incubated with OT–674 ( 0.01–10 mM) for 24–48 hours and exposed to 430 nm illumination. Cell viability was assessed by nuclear labeling and by MTT assay. In acellular assays, A2E was illuminated at 430 nm or incubated with a singlet oxygen generator (endoperoxide of 1,4 dimethylnaphthalene) with/without OT–674, a–tocopherol or Trolox.
By MTT assay, OT–674 protected A2E–laden RPE from blue light induced death, in a concentration–dependent manner. At 1 mM OT–674, viability of A2E–laden/430 nm irradiated RPE was increased 2–fold. In cell–free systems, OT–674 attenuated A2E photooxidation and inhibited singlet oxygen mediated–oxidation of A2E to an extent similar to that of a–tocopherol and the water–soluble analog Trolox.
We have shown that OT–674 is a potent antioxidant that suppresses photooxidative processes initiated in RPE cells by the lipofuscin fluorophore A2E. In particular, OT–674 is an effective quencher of singlet oxygen. By means of its antioxidant capability, OT–674 reduces RPE cell death in a culture model.
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