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Age-related macular degeneration—emerging pathogenetic and therapeutic concepts 

Authors: Karen M. Gehrs a;  Don H. Anderson bc;  Lincoln V. Johnson bc; Gregory S. Hageman ab
Affiliations:   a Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA, USA
b Center for the Study of Macular Degeneration, University of California, Santa Barbara, CA, USA
c Neuroscience Research Institute, University of California, Santa Barbara, CA, USA
DOI: 10.1080/07853890600946724
Publication Frequency: 8 issues per year
Published in: journal Annals of Medicine, Volume 38, Issue 7 November 2006 , pages 450 - 471
Subject: General Medicine;
Formats available: HTML (English) : PDF (English)
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Abstract

Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden.

Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes.

New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan.
Keywords: Age-related macular degeneration (AMD); basal laminar deposit (BLamD); Bruch's membrane; choroidal neovascularization; complement Factor B (BF); complement Factor H (CFH); drusen; epidemiology; genetics; geographic atrophy; inflammation; surgery
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