Current concepts in the pathogenesis of age-related macular degeneration
Abstract
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.
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The pathogenesis of age-related macular degeneration is not well known, although theories include oxidative stress, mitochondrial dysfunction, and inflammatory processes.
“The pathogenesis of age-related macular degeneration is not well known, although a number of theories have been put forward, including oxidative stress, mitochondrial dysfunction, and inflammatory processes.9–13”
From Age-related macular degeneration (2008) · cites this paper as [11]
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- Authors
- Zarbin, M. A.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Zarbin, Marco A.
- ORCID
- Zarbin, Marco A.
- Venue
- Archives of Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 2004-04-01
- Volume
- 122
- Issue
- 4
- Pages
- 598
- ISSN
- 0003-9950 (ISSN-L)
- OpenAlex
- W2155236757
- Semantic Scholar
- 9765dfeb4d6cd0fce1e3a627d4ac2e39f3b0d5ab
- Cited by
- 1,006
- References
- 271
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 19 · 2023: 15 · 2022: 41 · 2021: 33 · 2020: 37 · 2019: 28 · 2018: 31 · 2017: 49 · 2016: 47 · 2015: 53 · 2014: 62 · 2013: 61 · 2012: 82
- FWCI
- 53.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- age-related macular degeneration, pathogenesis, retinal pigment epithelium, oxidative stress, chronic inflammation, Bruch's membrane, extracellular matrix, choroidal neovascularization, geographic atrophy, aging, genetic susceptibility, animal models
- MeSH terms
- Aging, Extracellular Matrix, Humans, Macular Degeneration, Pigment Epithelium of Eye, Bruch Membrane, Oxidative Stress, Choroidal Neovascularization
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