Age-Related Macular Degeneration: A Complementopathy?

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. (C) 2015 S. Karger AG, Basel