September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells.
Author Affiliations & Notes
  • Gloriane Schnabolk
    Research, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States
  • Beth Coughlin
    Medical University of South Carolina, Charleston, South Carolina, United States
  • Kusumam Joseph
    Medical University of South Carolina, Charleston, South Carolina, United States
  • Himanshu Raikwar
    Medical University of South Carolina, Charleston, South Carolina, United States
  • Kannan Kunchithapautham
    Medical University of South Carolina, Charleston, South Carolina, United States
  • Krista Johnson
    Alexion Pharmaceuticals, Cheshire, Connecticut, United States
  • Kristi Moore
    Alexion Pharmaceuticals, Cheshire, Connecticut, United States
  • Yi Wang
    Alexion Pharmaceuticals, Cheshire, Connecticut, United States
  • Baerbel Rohrer
    Medical University of South Carolina, Charleston, South Carolina, United States
    Research, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, United States
  • Footnotes
    Commercial Relationships   Gloriane Schnabolk, None; Beth Coughlin, None; Kusumam Joseph, None; Himanshu Raikwar, None; Kannan Kunchithapautham, None; Krista Johnson, Alexion Pharmaceuticals (E); Kristi Moore, Alexion Pharmaceuticals (E); Yi Wang, Alexion Pharmaceuticals (E), Alexion Pharmaceuticals (P); Baerbel Rohrer, Alexion Pharmaceuticals (F), Alexion Pharmaceuticals (P)
  • Footnotes
    Support  VA1I01RX000444-05
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 478. doi:
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    • Get Citation

      Gloriane Schnabolk, Beth Coughlin, Kusumam Joseph, Himanshu Raikwar, Kannan Kunchithapautham, Krista Johnson, Kristi Moore, Yi Wang, Baerbel Rohrer; Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells.
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):478.

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

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Abstract

Purpose : Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is thought to contribute to AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by anaphylatoxin C5a receptor-expressing T-cells. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye.

Methods : CNV lesions were generated in C57BL/6 mice using laser photocoagulation in the presence and absence of anti-C5, anti-C5a, or 12B4 (control) blocking antibodies. CNV lesions were quantified by optical coherence tomography; and T-lymphocytes were characterized by QRT-PCR.

Results : CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells could be observed. Administration of anti-C5 or anti-C5a-blocking antibodies to reduce levels of C5a production in the eye, blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size (anti-C5: 3666 ± 359.9 pixels; anti-C5a: 3453 ± 253.8) when compared to control (12B4: 5572 ± 630.6; p ≤ 0.01) and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and T-cell proliferation was elevated in response to ocular proteins

Conclusions : Taken together, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Finally, understanding complement-mediated pathological mechanisms will aid in the development of a treatment for 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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