Aging is not a disease: distinguishing age-related macular degeneration from aging

Prog Retin Eye Res. 2013 Nov;37:68-89. doi: 10.1016/j.preteyeres.2013.07.003. Epub 2013 Aug 9.


Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

Keywords: Age-related macular degeneration; Aging; Homeostasis; Oxidative stress; Para-inflammation; Retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / physiology*
  • Bruch Membrane / pathology
  • Eye Diseases, Hereditary / pathology
  • Eye Proteins / metabolism
  • Humans
  • Lipid Metabolism / physiology
  • Macular Degeneration* / etiology
  • Macular Degeneration* / metabolism
  • Macular Degeneration* / pathology
  • Macular Degeneration* / physiopathology
  • Oxidative Stress / physiology
  • Retinal Drusen / pathology


  • Eye Proteins

Supplementary concepts

  • Basal Laminar Drusen