Purchase this article with an account.
Baerbel Rohrer, Nate Parsons, Gloriane Schnabolk, Steven Tomlinson; The complement system is dual-hatted, acting in both damage and repair processes in the murine model of choroidal neovascularization.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2123.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is the leading cause of blindness in the U.S. Polymorphisms in various complement components are associated with increased risk for AMD, and it has been hypothesized that an overactive complement system is partially responsible for the pathology of AMD. While it has been shown previously that complement components C3a and C5a promote choroidal neovascularization, it is important to note these components also play a role in tissue repair. Here we investigated the involvement of complement C3 activation and of C3a-receptor signaling in the development and regression of choroidal neovascularization (CNV).
Laser-induced photocoagulation was used to trigger CNV in wild type mice (C57BL/6J). CNV lesion size was measured by optical coherence tomography (OCT), performing exams regularly between days 5 and 28 after laser. Activation of C3 was inhibited during the induction phase of CNV (days 0-6) with CR2-Crry, and C3a-receptor engagement was inhibited during the regression phase of CNV (days 6-28) with a C3a-receptor antagonist (N2-[(2,2-diphenylethoxy)acetyl]-L-arginine, TFA).
CNV lesion size and subretinal fluid accumulation were significantly reduced in mice treated with CR2-Crry, confirming a role for downstream complement activation products in CNV growth. Interestingly, treatment of WT mice with the C3a-receptor antagonist TFA, significantly reduced repair of the lesion, with TFA-treated mice exhibiting prolonged fluid accumulation and fibrosis.
These data further support the importance of complement activation in controlling the magnitude of the injury response. However, it also indicates that C3a generation and receptor signaling may also be important for wound repair. These data add to the accumulating evidence that complement plays a dual role in the pathophysiology of many conditions, and this will need to be considered in selecting a complement inhibitory strategy for the treatment of AMD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only