Indirect antioxidant protection against photooxidative processes initiated in retinal pigment epithelial cells by a lipofuscin pigment.
Oxidative mechanisms are considered to contribute to the aging changes in retinal pigment epithelial (RPE) cells that underlie the pathogenesis of age-related macular degeneration. An important source of oxidative damage is likely to be the photoreactive pigments that progressively accumulate and constitute the lipofuscin of retinal pigment epithelial cells. Evidence for a link between RPE lipofuscin and cellular dysfunction is also provided by the understanding of disease progression in Stargardt disease. Using a culture model previously used to demonstrate photooxidative damage to retinal pigment epithelial cells that have accumulated the lipofuscin fluorophore A2E, it was shown that the propensity for cell death is increased under conditions that deplete cellular levels of glutathione. Additionally, sulforaphane, a phytochemical and inducer of phase 2 enzymes, protected RPE cells that accumulated A2E and were irradiated at 430 nm. The protection afforded by sulforaphane was paralleled by elevated levels of glutathione and increases in the activities of the phase 2 enzymes NAD(P)H:quinone reductase and glutathione-S-transferases. Moreover, transcriptional induction of NAD(P)H:quinone reductase was indicated by the increases in mRNA determined by real time RT-PCR. There has been considerable interest in the intake of carotenoids and antioxidant vitamins and the related incidence of age-related macular degeneration. The present results indicate that the indirect antioxidant activity of plant-derived phase 2 inducers also may be potentially important.
Zhou
Jilin
J
Department of Ophthalmology, Columbia University, New York, New York 10032, USA.
Gao
Xiangqun
X
Cai
Bolin
B
Sparrow
Janet R
JR
D000975:Antioxidants / Q000502:physiology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003124:Colorimetry; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates; D008062:Lipofuscin / Q000502:physiology*; D008268:Macular Degeneration / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000166:cytology*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology
D000975:Antioxidants; D017879:Isothiocyanates; D008062:Lipofuscin; D013454:Sulfoxides; D013861:Thiocyanates; D019328:Buthionine Sulfoximine; D005982:Glutathione Transferase; C016766:sulforaphane; D005978:Glutathione