title: Age-related macular degeneration: a complementopathy?
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.
authors.affiliation: University Eye Clinic Maastricht, Maastricht, The Netherlands.
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.forename: Tos T J M
authors.initials: TT
authors.lastname: Berendschot
mesh_terms: D000375:Aging / Q000502:physiology; D011416:Complement Factor D / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003170:Complement Pathway, Alternative; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism
chemical_list: D011416:Complement Factor D