(Note: Emphasis in all quotes are ours)
"As oxidative stress defense mechanisms deteriorate with age, oxidative modifications may gradually lock these and other proteins to to Bruch's membrane with crosslinks, preventing normal turnover and initiating drusen development. The photooxidative environment in the retina and the lipid-rich photoreceptor outer segments 10% of which are phagocytosed daily by the RPE provide an excellent source of radical oxygen species. Waste product from the RPE and blood components from the choriocapillaris provide a ready source of extracellular material for oxidative modification and drusen formation"
"These data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation."
"The autofluorescent pigments that accumulate in retinal pigment epithelial cells with aging and in some retinal disorders, have been implicated in the etiology of macular degeneration. The major constituent is the fluorophore A2E... Light-exposed A2E-laden RPE exhibit a propensity for apoptosis with light in the blue region of the spectrum being most damaging. Efforts to understand the events precipitating the death of the cells have revealed that during irradiation (430 nm), A2E self-generates singlet oxygen with the latter in turn reacting with A2E to generate epoxides at carbon-carbon double bonds.
It is well established that RPE cells that have accumulated A2E are subject to blue light mediated injury and we showed that at least one of the cellular macromolecules damaged is DNA.
The oxidative damage to which all cells are subjected is considered to be a significant cause of an age-related decline in cell function. Nevertheless, as a nonreplicating cell that is exposed to wavelengths of light in the visible spectrum and accumulates a naturally occurring photoreactive chromophore with age, the RPE cell may be anomalous. The damage that A2E epoxidation bestows on the RPE cell may be the element linking the associations between RPE atrophy and lipofuscin accumulation, on the one hand, and AMD and light exposure, on the other. Photoxidative mechanisms involving A2E may also underlie the known susceptibility of RPE to blue light damage in vivo.
"The photoreceptors in the retina, designed to initiate the cascade of events which link the incoming light to the sensation of 'vision', are susceptible to damage by light, particularly blue light. The damage can lead to cell death and diseases. The turnover of retinal, an essential element of the visual process, is the basis of the events that lead to damage. Free retinal, absorbing in the blue region of the visible spectrum, is phototoxic, and is a precursor of the (photo)toxic compound A2E, which specifically targets cytochrome oxidase and thereby induces cell death by apoptosis."
"The blue light-filtering molecules lutein and zeaxanthin are tailor-made substances protecting the retina. In vitro, they protect cytochrome oxidase against the permanent damage caused by A2E in combination with light. These novel findings should enable us to prevent or cure the dry form of age-related macular degeneration, the leading cause of severe visual impairment in humans living in developed countries."
"Lutein and zeaxanthin are the predominant carotenoids in the human macula lutea. Epidemiological data suggest that an increased intake of a lutein-rich diet correlates with a diminished risk for age-related macular degeneration, a major cause of impaired vision in the elderly. Filtering of blue light has been proposed as a possible mechanism of protection."
"It is concluded that the accumulation of lipofuscin within secondary lysosomes of RPE sensitizes these cells to blue light by inducing photo-oxidative alterations of their lysosomal membranes resulting in a presumed leakage of lysosomal contents to the cytosol with ensuing cellular degeneration of apoptotic type. The suggested mechanism may have bearings on the development of age-related macular degeneration.".
"CONCLUSION: Blue wavelength light without exogenous protoporphyrin IX has a cytotoxic effect on confluent cultures of retinal pigment epithelium, suggesting that endogenous photosensitizers may be present in retinal pigment epithelial cells. Protoporphyrin IX has an additive cytotoxic effect in the presence of blue light, suggesting that this photosensitizer is capable of mediating blue-light-induced retinal pigment epithelial damage. Since protoporphyrin IX is present in blood and tissue fluids, and the retina is chronically exposed to light, protoporphyrin IX-mediated free radical formation may occur in vivo and may play a role in retinal pigment epithelial changes that occur early in the pathogenesis of age-related macular degeneration."
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