Age-Related Macular Degeneration
(ARMD)
Age-Related Macular Degeneration (ARMD) is the leading cause of blindness in the elderly. It has been estimated that ARMD will afflict more than 20 million people worldwide by 2000 or shortly thereafter. The earlier stage "dry form of ARMD" involves development of yellow spots (drusen) in the retina (~85-90% of the cases). The later stage "wet form of ARMD" involves vascular abnormalities, retinal pigment epithelium disturbance and detachment, neovascularization, subretinal hemorrhage and disciform scar formation in the retina (~10-15% of the cases).
The prevalence of ARMD appears to be increasing owing in part to the aging of the general population and increased life-expectancies. Genetic and other prognostic tests, including blood and tear analysis, are needed to identify individuals who are at-risk for developing dry and wet ARMD. Prognostic markers could facilitate preventive and/or more effective treatment of ARMD patients. Moreover, if effective, safe, early stage treatment or preventive approaches were available for ARMD, then more people would seek vision evaluation and protection earlier before their vision is lost.
The exact cause of ARMD is unknown but a contribution from oxidative stress seems likely. Retinas from ARMD patients contain more lipofuscin - a by-product from the reaction of lipids and oxidants - than the retinas of non-ARMD patients. Moreover, trephined buttons from the human retina reveal age-dependent increases in susceptibility to lipid peroxidation induced in vitro by excess iron in the posterior (but not the peripheral) region of the retina. Since the level of 22:bn-3 lipids in the macular region is less than in the peripheral retina, this finding suggests that the macula may be more sensitive to lipid peroxidation than other tissues. In addition, thiobarbituric acid reactive substances (TBARS) - a measure of lipid peroxidation - were higher in the plasma of macques that had greater than 10 drusen than in control macques with less drusen.
Like ARMD, oxidative stress and a number of factors that increase oxidative stress, such as iron accumulation, increase progressively with aging. The potent glutathione (GSH) redox system also appears to be depressed in ARMD and aging individuals (Figure 1).
In summary, because ARMD is common and because the consequences of blindness are so devastating, determination of the ways that oxidative stress can be reduced in the eye is needed. We are pursuing ways to effectively increase the activity of the glutathione redox system which should reduce ocular oxidative stress and perhaps prevent the development or progression of ARMD.
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