September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The complement system is dual-hatted, acting in both damage and repair processes in the murine model of choroidal neovascularization.
Author Affiliations & Notes
  • Baerbel Rohrer
    Med Univ of South Carolina, Charleston, South Carolina, United States
    Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States
  • Nate Parsons
    Med Univ of South Carolina, Charleston, South Carolina, United States
    Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States
  • Gloriane Schnabolk
    Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States
    Med Univ of South Carolina, Charleston, South Carolina, United States
  • Steven Tomlinson
    Med Univ of South Carolina, Charleston, South Carolina, United States
    Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States
  • Footnotes
    Commercial Relationships   Baerbel Rohrer, Alexion (P); Nate Parsons, None; Gloriane Schnabolk, None; Steven Tomlinson, Alexion (P)
  • Footnotes
    Support  This work was sponsored in part by a Department of Veterans Affairs merit award RX000444, a National Institutes of Health grant EY019320, the Feldberg Endowment as well as an unrestricted grant to MUSC from Research to Prevent Blindness (RPB), New York, NY.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2123. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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  • Supplements
Abstract

Purpose : 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).

Methods : 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).

Results : 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.

Conclusions : 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.

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