Current Concepts in the Pathogenesis of Age-Related Macular Degeneration | Genetics and Genomics | JAMA Ophthalmology | JAMA Network
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Mechanisms of Ophthalmologic Disease
April 2004

Current Concepts in the Pathogenesis of Age-Related Macular Degeneration

Author Affiliations

From the Institute of Ophthalmology and Visual Science at the New JerseyMedical School, University of Medicine and Dentistry of New Jersey, Newark.The author has no relevant financial interest in this article.



Arch Ophthalmol. 2004;122(4):598-614. doi:10.1001/archopht.122.4.598

Objective  To review and synthesize information concerning the pathogenesis ofage-related macular degeneration (AMD).

Methods  Review of the English-language literature.

Results  Five concepts relevant to the cell biology of AMD are as follows: (1)AMD involves aging changes plus additional pathological changes (ie, AMD isnot just an aging change); (2) in aging and AMD, oxidative stress causes retinalpigment epithelial (RPE) and, possibly, choriocapillaris injury; (3) in AMD(and perhaps in aging), RPE and, possibly, choriocapillaris injury resultsin a chronic inflammatory response within the Bruch membrane and the choroid;(4) in AMD, RPE and, possibly, choriocapillaris injury and inflammation leadto formation of an abnormal extracellular matrix (ECM), which causes altereddiffusion of nutrients to the retina and RPE, possibly precipitating furtherRPE and retinal damage; and (5) the abnormal ECM results in altered RPE-choriocapillarisbehavior leading ultimately to atrophy of the retina, RPE, and choriocapillarisand/or choroidal new vessel growth. In this sequence of events, both the environmentand multiple genes can alter a patient's susceptibility to AMD. Implicit inthis characterization of AMD pathogenesis is the concept that there is linearprogression from one stage of the disease to the next. This assumption maybe incorrect, and different biochemical pathways leading to geographic atrophyand/or choroidal new vessels may operate simultaneously.

Conclusions  Better knowledge of AMD cell biology will lead to better treatmentsfor AMD at all stages of the disease. Many unanswered questions regardingAMD pathogenesis remain. Multiple animal models and in vitro models of specificaspects of AMD are needed to make rapid progress in developing effective therapiesfor different stages of the disease.