Dopa and oxygen inhibit proliferation of retinal pigment epithelial cells, fibroblasts and endothelial cells in vitro.
Some quinones catalyze superoxide formation in a futile cycle involving electron transfer to molecular oxygen. If the quinolic precursors of melanin participated in the futile cycle, the high ambient oxygen surrounding postnatal RPE would make continued melanogenesis risk for the retina. To probe the possibility that arrest of melanogenesis in postnatal RPE is a protective mechanism, we assayed the growth rates of RPE cells, aortic endothelial cells and skin fibroblasts exposed to 0, 10, 50, 100 and 250 microM dopa. To assess the contribution of the futile cycle, we studied the effects of oxygen concentration and the antioxidants, superoxide dismutase and catalase. We found that all three cell types were significantly and dose-dependently inhibited by dopa and that the effects of dopa were oxygen dependent. The powerful inhibition of RPE cells by dopa was counteracted by inclusion of superoxide dismutase and catalase, but not by an inhibitor of dopa oxidase (phenylthiourea), indicating that the mechanism of growth suppression did not involve melanogenesis but, rather, dopa-dependent formation of superoxide in the media. Endothelial cells were more sensitive to the dopa-mediated oxidative damage than were RPE cells or fibroblasts. Fibroblasts were most affected by oxygen alone, and least affected by dopa. These data suggest that suppression of melanogenesis in the postnatal RPE may be an important mechanism for preventing oxidative damage to the retina and the choriocapillaris We propose that the generation of oxygen radicals by the quinone futile cycle is a viable model of the damage of cells in culture by dopa.
Akeo
K
K
Eye Research Institute, Boston, MA 02114.
Ebenstein
D B
DB
Dorey
C K
CK
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000187:drug effects; D012867:Skin / Q000166:cytology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D004295:Dihydroxyphenylalanine; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen