Pathway-based therapies for age-related macular degeneration

An integrated survey of emerging treatment alternatives

Marco A. Zarbin, Philip J Rosenfeld

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Purpose: To review treatments under development for age-related macular degeneration (AMD) in the context of current knowledge of AMD pathogenesis. Methods: Review of the scientific literature published in English. Results: Steps in AMD pathogenesis that appear to be good targets for drug development include 1) oxidative damage; 2) lipofuscin accumulation; 3) chronic inflammation; 4) mutations in the complement pathway; and 5) noncomplement mutations that influence chronic inflammation and/or oxidative damage (e.g., mitochondria and extracellular matrix structure). Steps in neovascularization that can be targeted for drug development and combination therapy include 1) angiogenic factor production; 2) factor release; 3) binding of factors to extracellular receptors (and activation of intracellular signaling after receptor binding); 4) endothelial cell activation (and basement membrane degradation); 5) endothelial cell proliferation; 6) directed endothelial cell migration; 7) extracellular matrix remodeling; 8) tube formation; and 9) vascular stabilization. Conclusion: The era of pathway-based therapy for the early and late stages of AMD has begun. At each step in the pathway, a new treatment could be developed, but complete inhibition of disease progression will likely require a combination of the various treatments. Combination therapy will likely supplant monotherapy as the treatment of choice because the clinical benefits (visual acuity and frequency of treatment) will likely be superior to monotherapy in preventing the late-stage complications of AMD.

Original languageEnglish
Pages (from-to)1350-1367
Number of pages18
JournalRetina
Volume30
Issue number9
DOIs
StatePublished - Oct 1 2010

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Macular Degeneration
Endothelial Cells
Therapeutics
Extracellular Matrix
Inflammation
Lipofuscin
Mutation
Angiogenesis Inducing Agents
Surveys and Questionnaires
Combination Drug Therapy
Basement Membrane
Visual Acuity
Cell Movement
Blood Vessels
Disease Progression
Mitochondria
Cell Proliferation
Cell Membrane
Pharmaceutical Preparations

Keywords

  • age-related macular degeneration
  • angiogenesis
  • choroidal neovascularization
  • complement
  • geographic atrophy
  • neuroprotection
  • oxidative damage
  • treatment

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Pathway-based therapies for age-related macular degeneration : An integrated survey of emerging treatment alternatives. / Zarbin, Marco A.; Rosenfeld, Philip J.

In: Retina, Vol. 30, No. 9, 01.10.2010, p. 1350-1367.

Research output: Contribution to journalArticle

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