(Note: Emphasis in all quotes are ours)
"This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD).... The phototoxicity of lipofuscin, a group of complex autofluorescent lipid/protein aggregates that accumulate in the retinal pigment epithelium, is described and evidence is presented suggesting that intracellular lipofuscin is toxic to these cells, thus supporting a role for lipofuscin in aging and AMD."
"The outer retina is inherently at risk from photooxidative damage due to continual exposure to high fluxes of incident light, high concentrations of oxygen, and the presence of a number of potential photosensitizers. Moreover it contains high concentration of polyunsaturated fatty acids, including docosahexaenomic acid, which are extremely susceptible to peroxidation.... Lipofuscin which accumulates during ageing in the RPE is a potent photosensitizer, which photogenerates singlet oxygen, superoxide anion, hydrogen and lipid peroxides."
"Age-related macular degeneration (ARMD) is a degenerative disease
that causes severe visual impairment in one fourth of the population over
65. Some predisposing genetic and environmental factors, such as
oxidative stress, low eye pigmentation, excessive light exposure, and
smoking, have been identified"
"In fact, at concentrations similar to those found in aged human RPE,
A2E does not cause cell death and alters lysosomal integrity only on
exposure to blue light"
"To compensate for the damaging effects of light, RPE cells must
perform the burdensome task of phagocytosing and degrading 7-10% of the
cone and rod outer segment (OS) biomass, shed in a circadian fashion.
Because RPE cells are postmitotic in the eye, this is a life-long task
that must be completed every 24 h to prevent gradual accumulation of OS
remnants"
"Because of the 24 h circadian rhythm of OS phagocytosis in the
eye, a delay of OS degradation similar to the one we observed in cultured
RPE cells would cause, over time, an increasing build up of undigested
lipids. This adverse effect of A2E accumulation on the RPE clearance
function may constitute an important factor in the development of ARMD"
Photodamage to Human Retinal Pigment Epithelium (RPE) Cells by A2-E, a Retinoid Component of Lipofuscin. Schutt F, Davies S, Kopitz J, Holz FG, Boulton ME. Investigative Ophthalmology and Visual Science 2000;41(8):2303-8"The accumulation of lipofuscin within postmitotic cells is a recognized hallmark of aging occurring with a rate inversely related to longevity....Because it is undegradable and cannot be removed via exocytosis, lipofuscin accumulation in postmitotic cells is inevitable"
"Lipofuscin is a fluorochrome and may sensitize lysosomes to visible light, a process potentially important for the pathogenesis of age-related macular degeneration."
"The phototoxic properties of A2-E were determined by exposing
A2-E-free and A2-E-fed RPE cell cultures to short wavelength visible light (400-500 nm)
and assessing cell viability and lysosomal integrity....Exposure of A2-E-fed cells to
light resulted in a significant loss of cell viability by 72 hours, which was not observed
in either RPE cells maintained in the dark or A2-E-free cultures exposed to light.
Toxicity was associated with a loss of lysosomal integrity.
CONCLUSIONS: A2-E is detrimental to RPE cell function by a variety of mechanisms:
inhibition of lysosomal degradative capacity, loss of membrane integrity, and
phototoxicity. Such mechanisms could contribute to retinal aging as well as retinal
diseases associated with excessive lipofuscin accumulation -for example, Age-Related
Macular Degeneration and Stargardt's disease."
"In old age, lipofuscin accumulation may become quite substantial. It
has been suggested that pronounced accumulation of lipofuscin is related to decreased RPE
function and,
possibly, to age-related macular degeneration."
"CONCLUSIONS: Severe lipofuscin accumulation of RPE cells appears to result in
a greatly decreased phagocytic capacity. The resulting reduction in ability to cope
with the needs of the overlying photoreceptor cells, in order to eliminate the obsolete
tips of their POS, may well be of significance in the development of age-related macular
degeneration."
Biosynthesis of a Major Lipofuscin Fluorophore in Mice and Humans with ABCR-Mediated Retinal and Macular Degeneration. Mata NL, Weng J, Travis GH. Proceedings of the National Academy of Sciences U S A. 2000; 97(13):7154-9"The integrity of the retinal pigment epithelium, especially that of the macula is essential for the preservation of vision into old age. The chronic exposure to sunlight and peroxidized lipids from phagocytized photoreceptor outer segments imposes a high level of oxidative stress on the retinal tissues, which increases with age as antioxidant protection declines and therefore could accelerate apoptosis."
"Increased accumulation of lipofuscin in cells of the retinal pigment epithelium (RPE) is seen in several forms of macular degeneration, a common cause of blindness in humans."
"These data suggest that humans with retinal or macular degeneration caused by loss of RmP function may slow progression of their disease by limiting exposure to light"
"Macular Pigment (MP) is composed of the hydroxy-carotenoids lutein and zeaxanthin. Although it appears that all humans have some quantity of these pigments within their retina, foveal concentrations tend to vary quite dramatically. This wide individual variability has prompted questions regarding possible functional consequences. At least two major nonexclusive hypotheses regarding the function of MP have been proposed. The "protection hypothesis" has received the most attention and is based on the possibility that MP could reduce the cumulative effects of damage due to light and oxygen and retard the development of age-related eye disease."
Note: more recent references can be found in the section marked - For Therapists...