Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: relation with docosahexaenoic acid.
OBJECTIVE
Oxidative stress has been proposed as a major pathogenic factor in age-related macular degeneration (AMD), the leading cause of vision loss among elderly people of western European ancestry. Lutein (LUT) and zeaxanthin (ZEA), major components in macular pigment, are among the retinal antioxidants. Though xanthophyll intake may reduce the likelihood of having advanced AMD, direct evidence of neuroprotection is lacking. Prior work has shown that docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, delays apoptosis and promotes differentiation of photoreceptors. This study was conducted to investigate whether LUT, ZEA, and beta-carotene (BC), major dietary carotenoids protect photoreceptors from oxidative stress and whether this protection is synergistic with that of DHA.


METHODS
Pure rat retinal neurons in culture, supplemented with LUT, ZEA, or BC, with or without DHA, were subjected to oxidative stress induced with paraquat and hydrogen peroxide. Apoptosis, preservation of mitochondrial membrane potential, cytochrome c translocation, and opsin expression were evaluated.


RESULTS
Pretreatment with DHA, LUT, ZEA, and BC reduced oxidative stress-induced apoptosis in photoreceptors, preserved mitochondrial potential, and prevented cytochrome c release from mitochondria. ZEA and LUT also enhanced photoreceptor differentiation. In control cultures, photoreceptors failed to grow their characteristic outer segments; addition of DHA, ZEA, or LUT increased opsin expression and promoted the development of outer-segment-like processes.


CONCLUSIONS
These results show for the first time the direct neuroprotection of photoreceptors by xanthophylls and suggest that ZEA and LUT, along with DHA, are important environmental influences that together promote photoreceptor survival and differentiation.
Chucair
Ana J
AJ
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) and Universidad Nacional del Sur (UNS), Bahía Blanca, Buenos Aires, Argentina.
Rotstein
Nora P
NP
Sangiovanni
John Paul
JP
During
Alexandrine
A
Chew
Emily Y
EY
Politi
Luis E
LE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D006861:Hydrogen Peroxide / Q000633:toxicity; D014975:Lutein / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017299:Rod Opsins / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology*; D065146:Zeaxanthins
D017299:Rod Opsins; D024341:Xanthophylls; D065146:Zeaxanthins; D004281:Docosahexaenoic Acids; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D010269:Paraquat; D014975:Lutein