title: Synthetic carotenoid derivatives prevent photosensitised killing of retinal pigment epithelial cells more effectively than lutein.
abstract: We studied the photosensitised killing of retinal pigment epithelial (RPE) cells using two photosensitisers that localise in lysosomes. The ARPE-19 cell line was photosensitised using either acridine orange or cis-di(4-sulfonatophenyl)diphenylporphine. We then measured the amount of photoprotection provided to RPE cells by five synthetic carotenoid derivatives and by lutein. The synthetic carotenoid derivatives studied were the Girard's reagent P derivative (GRP) of retinal (GRP-retinal), the GRP derivative of beta-apo-8'-carotenal (GRP-carotenal), the Girard's reagent T derivative of beta-apo-8'-carotenal (GRT-carotenal), the GRP derivative of canthaxanthin ((GRP)2-canthaxanthin) and the dansyl hydrazine derivative of beta-apo-8'-carotenal (dansyl-carotenal). We found that GRP-carotenal, GRT-carotenal (GRP)2-canthaxanthin and dansyl-carotenal were effective photoprotectors. All of these carotenoids had large singlet-oxygen quenching constants and had chemical structures designed to localise either in mitochondria or in lysosomes. In contrast, lutein and GRP-retinal were not effective photoprotectors. The failure of GRP-retinal to provide significant photoprotection may have been due to its relatively low singlet-oxygen quenching constant. Lutein is a potent singlet-oxygen quencher, but may not have provided significant photoprotection in this model because the lutein may have had a different subcellular distribution than the photosensitisers used.
authors.affiliation: Medical Service, Edward Hines, Jr., Department of Veterans Affairs Hospital, Hines, IL 60141, USA. jeff.kanofsky@med.va.gov
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Kanofsky
authors.forename: Paul D
authors.initials: PD
authors.lastname: Sima
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008027:Light; D014975:Lutein / Q000493:pharmacokinetics / Q000494:pharmacology*; D017319:Photosensitizing Agents; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017319:Photosensitizing Agents; D011837:Radiation-Protective Agents; D026082:Singlet Oxygen; D002338:Carotenoids; D014975:Lutein