Current concepts in the pathogenesis of age-related macular degeneration.
OBJECTIVE
To review and synthesize information concerning the pathogenesis of age-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 is not just an aging change); (2) in aging and AMD, oxidative stress causes retinal pigment epithelial (RPE) and, possibly, choriocapillaris injury; (3) in AMD (and perhaps in aging), RPE and, possibly, choriocapillaris injury results in a chronic inflammatory response within the Bruch membrane and the choroid; (4) in AMD, RPE and, possibly, choriocapillaris injury and inflammation lead to formation of an abnormal extracellular matrix (ECM), which causes altered diffusion of nutrients to the retina and RPE, possibly precipitating further RPE and retinal damage; and (5) the abnormal ECM results in altered RPE-choriocapillaris behavior leading ultimately to atrophy of the retina, RPE, and choriocapillaris and/or choroidal new vessel growth. In this sequence of events, both the environment and multiple genes can alter a patient's susceptibility to AMD. Implicit in this characterization of AMD pathogenesis is the concept that there is linear progression from one stage of the disease to the next. This assumption may be incorrect, and different biochemical pathways leading to geographic atrophy and/or choroidal new vessels may operate simultaneously.


CONCLUSIONS
Better knowledge of AMD cell biology will lead to better treatments for AMD at all stages of the disease. Many unanswered questions regarding AMD pathogenesis remain. Multiple animal models and in vitro models of specific aspects of AMD are needed to make rapid progress in developing effective therapies for different stages of the disease.
Zarbin
Marco A
MA
Institute of Ophthalmology and Visual Science at the New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 90 Bergen Street, Suite 6100, Newark, NJ 07103-2499, USA. zarbin@njmsa.umdnj.edu
D000375:Aging / Q000378:metabolism; D016570:Bruch Membrane / Q000378:metabolism / Q000473:pathology; D020256:Choroidal Neovascularization / Q000150:complications; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology* / Q000378:metabolism; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000473:pathology