Therapeutic targeting of the complement system in age-related macular degeneration: a review.
The last decade has produced pivotal change in our understanding of the molecular mechanisms underlying age-related macular degeneration (AMD), a leading cause of global blindness. In this time, the complement system has featured as a unifying theme for several elements of new evidence: initially, the discovery of complement proteins within drusen and subsequently, the association between AMD and mutations in various complement pathway genes, most notably complement factor H. Increasingly, a wealth of data are pointing towards a role for chronic local inflammation and complement activation in the patho-aetiology of AMD. These findings have paved the way for the exploration of a new paradigm of therapy in AMD management; targeting of specific molecular constituents in the complement pathway thus producing dampening or inhibition of the inflammatory response. Such an approach has the potential to intervene earlier in the disease process and ideally before vision is compromised. In this review we discuss the role of the complement system in AMD, novel therapies in preclinical evaluation and clinical trial, and whether these have a part to play in reducing the burden of disease.
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. rtroutbeck@gmail.com
Robyn
R
Troutbeck
Salmaan
S
Al-Qureshi
Robyn H
RH
Guymer
D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism
D051056:Complement Inactivating Agents; D003165:Complement System Proteins