Synthetic carotenoid derivatives prevent photosensitised killing of retinal pigment epithelial cells more effectively than lutein

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 β-apo-8′-carotenal (GRP-carotenal), the Girard's reagent T derivative of β-apo-8′-carotenal (GRT-carotenal), the GRP derivative of canthaxanthin ((GRP)2-canthaxanthin) and the dansyl hydrazine derivative of β-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.