Age-related macular degeneration The Irish Medical News. July 2007
Danielle Barron quoting Dr. Stephen Beatty.
"The blue part of the spectrum of visible light has the highest energy and is therefore most damaging to the retina. The significance of this is that it is photo-oxidative stress, or cumulative exposure to free radicals from blue light, over a lifetime that causes AMD', he explained."
Oxidative Damage and Protection of the RPE.
Prog Retin Eye Res 2000 Mar;19(2):205-21
Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP.
"In summary, all individuals with different genetic backgrounds all face the burden of high oxidative stress in their RPE. Once the protection from the antioxidant system has been overwhelmed, apoptosis can be triggered by a mechanism involving the mitochondrial signalling. Accumulation of sublethal oxidative injury potentiates oxidative injury an affected RPE cells" Abstract
Retinal Photodamage. J Photochem Photobiol B 2001 Nov 15;64(2-3):144-61
Boulton M, Rozanowska M, Rozanowski B.
"The retina represents a paradox, in that, while light and oxygen are essential for vision, these conditions also favour the formation of reactive oxygen species leading to photochemical damage to the retina. Such light damage seems to be multi-factorial and is dependent on the photoreactivity of a variety of chromophores endogenous to the retina."
"Light is essential for vision but the trade off is the generation of potentially damaging reactive oxygen species within the eye."
"It is tempting to suggest that the inter-individual variability in the onset and severity of disease dependent on both light exposure and the concentration of retinal chromophores."
"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." Abstract
The Lipofuscin Component A2E Selectively Inhibits Phagolysosomal Degradation of
Photoreceptor Phospholipid by the Retinal Pigment Epithelium RPE).
Proc Natl Acad Sci U S A 2002 Mar 19;99(6):3842-7
Finnemann SC, Leung LW, Rodriguez-Boulan E.
"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" Full Article
Lipofuscin: Mechanisms of Age-Related Accumulation and Influence on Cell Function.
Free Radic Biol Med 2002 Sep 1;33(5):611-9
Brunk UT, Terman A.
"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." Abstract
Photodamage to Human Retinal Pigment Epithelium (RPE) Cells by A2-E,
a Retinoid Component of Lipofuscin.
Investigative Ophthalmology and Visual Science 2000;41(8):2303-8
Schutt F, Davies S, Kopitz J, Holz FG, Boulton ME
"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." Abstract
Lipofuscin Accumulation in Cultured Retinal Pigment Epithelial Cells Reduces
Their Phagocytic Capacity. Current Eye Research 1998; 17(8):851-7
Sundelin S, Wihlmark U, Nilsson SE, Brunk UT
"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." Abstract
Bcl-2 Overexpression Increases Survival in Human Retinal Pigment
Epithelial Cells Exposed to H2O2. Exp Eye Res 2002 Jun;74(6):663-9
Godley BF, Jin GF, Guo YS, Hurst JS.
"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." Abstract
Biosynthesis of a Major Lipofuscin Fluorophore in Mice and Humans with ABCR-Mediated
Retinal and Macular Degeneration.
Proceedings of the National Academy of Sciences U S A. 2000; 97(13):7154-9
Mata NL, Weng J, Travis GH
"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" Abstract
Carotenoids in the Retina and Lens: Possible Acute and Chronic Effects on
Human Visual Performance. >Arch Biochem Biophys 2001; 385(1):41-6
Hammond BR Jr, Wooten BR, Curran-Celentano J.
"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." Abstract
Note: more recent references on the risk of eye damage from light therapy can be found in the section marked - For Therapists