Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy.

ABSTRACT: Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, clas

SUBMITTER: Katschke KJ 

PROVIDER: S-EPMC5943270 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature