Age-related macular degeneration: a complementopathy?

Ophthalmic Res. 2015;54(2):64-73. doi: 10.1159/000432401. Epub 2015 Jul 9.

Abstract

Age-related macular degeneration (AMD) is a progressive eye disease affecting many elderly individuals. It has a multifactorial pathogenesis and is associated with numerous environmental (e.g. smoking, light and nutrition) and genetic risk factors. A breakthrough in the mechanisms causing AMD is emerging; the involvement of the alternative pathway of the complement system appears to play a pivotal role. This has led to the statement that AMD is a disease caused by a hyperactive complement system, allowing the term 'complementopathy' to define it more precisely. Abundant evidence includes: the identification of drusen components as activators of complement, immunohistochemical data showing the presence of many species of the complement system in the retinal pigment epithelium-Bruch's membrane-choroidocapillary region of AMD eyes, a strong association of AMD with certain genetic complement protein variants, raised complement levels in blood from AMD patients and the preliminary successful treatments of geographic atrophy with complement factor D (FD) inhibitors. FD is the rate-limiting enzyme of the alternative complement pathway, and is produced by adipose tissue. Recent findings suggest that nutrition may play a role in controlling the level of FD in the circulation. Addressing modifiable risk factors such as smoking and nutrition may thus offer opportunities for the prevention of AMD.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Complement Factor D / antagonists & inhibitors*
  • Complement Factor D / metabolism
  • Complement Pathway, Alternative*
  • Humans
  • Macular Degeneration / genetics
  • Macular Degeneration / immunology*
  • Macular Degeneration / metabolism
  • Retinal Pigment Epithelium / metabolism

Substances

  • Complement Factor D