The toxic effect of light on retinal photoreceptors, its mechanism and the protection by endogenous indolamines

Abstract

Light absorption by the outer segment of retinal rod photoreceptors initiates visual sensory stimulation, but it may
as well induce, once these cell segments are detached from the main cell body, a less well known but fatally toxic oxidative stress which we monitored by the use of the oxidation-sensitive probe Rhodamine 123. The molecular mechanism of the light induced oxidative damage is initiated by an intermediate of activated rhodopsin without requiring the presence of GTP-dependent proteins. Since no oxidative damage is produced when light is falling on outer segments as part of intact cells, we postulated
the existence, within the photoreceptors inner segment of a molecular mechanism contrasting the toxic prerogative of light, thus protecting photoreceptors. It is known that photoreceptors synthesize indoleamines capable of antioxidant activity, and we investigated whether such endogenous substances would actually provide a protective role. This possibility was suggested by our earlier finding that the application of exogenous melatonin and its precursor N-acetyl serotonin effectively protected the photoreceptors outer segment from the light-induced damage. Subsequently, by either inhibiting or stimulating the synthesis of endogenous melatonin within rod receptor cells of adult Rana pipiens, we verify whether endogenous indoleamines could afford protection of the whole photoreceptor against the visible light-induced damage. It was found that by inhibiting melatonin production, a dose-dependent increase in oxidant generation and membrane damage was observed in intact rods. On the contrary, the stimulation of photoreceptor’ synthesis of melatonin almost completely abolishes the oxidative stress and damage induced by visible light. Conclusions: Our results provide the first direct evidence that endogenous indoleamines protect photoreceptors from oxidative stress and damage induced by visible light.