Age-related macular degeneration: review of pathogenesis

Eur J Ophthalmol. 1998 Oct-Dec;8(4):199-206.


Age-related macular degeneration is a condition (a) characterized by accumulation of membranous debris on both sides of the retinal pigment epithelium (RPE) basement membrane. Clinical manifestations of drusen, atrophy of the RPE/choriocapillaris, RPE detachment, and choroidal new vessel (CNV) formation occur after age 50 years. A hypothetical pathogenic sequence of events consistent with known data is: 1) RPE dysfunction (e.g., precipitated by an inherited susceptibility and/or environmental exposure); 2) accumulation of intracellular material in the RPE (e.g., accumulation of normal substrate material that is not enzymatically degraded properly vs. abnormal substrate material); 3) abnormal accumulation of extracellular material (basal laminar and basal linear deposit); 4) change in Bruch's membrane composition (e.g., increased lipid deposition and protein crosslinking); 5) change in Bruch's membrane parmeability to nutrients (e.g., impaired diffusion of water soluble plasma constituents across Bruch's membrane); and 6) response of the RPE to metabolic distress (i.e., atrophy vs. CNV growth). Histopathological and clinical studies indicate that areas of choroidal ischemia often are seen near CNVs in AMD patients. In response to decreased oxygen delivery/metabolic "distress", the RPE may elaborate substances leading to CNV growth. Perhaps RPE atrophy, followed by choriocapillaris and photoreceptor atrophy, is a response to decreased nutrients/increasing metabolic abnormalities in areas of excessive accumulation of extracellular debris. Unanswered questions regarding AMD include: 1) is AMD an ocular manifestation of a systemic disease or purely an ocular disease?; 2) what determines whether CNVs vs. atrophy of the RPE-choriocapillaris-photoreceptors develops?; and 3) what induces the maturation of CNVs into an inactive scar, and what limits the growth of most CNVs to the area centralis?

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Cell Membrane Permeability
  • Choroid / blood supply
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / pathology
  • Humans
  • Macular Degeneration / etiology*
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Middle Aged
  • Photoreceptor Cells / metabolism
  • Photoreceptor Cells / pathology
  • Pigment Epithelium of Eye / metabolism
  • Pigment Epithelium of Eye / pathology