June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Locally produced complement C1q regulates corneal epithelium wound healing
Author Affiliations & Notes
  • Jin Y. Chen
    Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States
  • Yan Sun
    Ophthalmic Research, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Connie Tam
    Ophthalmic Research, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Feng Lin
    Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Jin Chen None; Yan Sun None; Connie Tam None; Feng Lin None
  • Footnotes
    Support  NIH Grant EY030111(FL); NIH Grant EY032458(FL)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1880. doi:
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    • Get Citation

      Jin Y. Chen, Yan Sun, Connie Tam, Feng Lin; Locally produced complement C1q regulates corneal epithelium wound healing. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1880.

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

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Abstract

Purpose : Impaired corneal epithelium wound healing is a significant clinical problem and could lead to vision loss, but the underlying mechanisms are poorly understood. C1q is a complement component primarily produced by myeloid cells but also expressed in other cell types including epithelial cells. However, the potential role of C1q in regulating corneal wound healing was completely unknown.

Methods : Corneal wound healing was studied in wild-type (WT) and C1q knockout (KO) mice after epithelium abrasion. The local cytokine expression profiles between WT and C1q KOs were compared. To distinguish the role of systemic C1q produced by myeloid cells in the blood from local C1q produced in the cornea, WT and C1q KO bone marrow chimeric mice were generated and studied in the model. C1q expression by both mouse and human corneal epithelial cells was examined. C1q was knocked out in human corneal epithelial cells and wound healing rate was compared between the resultant C1q KO and WT cells. Finally, C1q-specific or control siRNA nanoparticles were injected into the conjunctiva of WT mice for treatment studies.

Results : C1q KO mice showed accelerated wound healing after corneal epithelium abrasion with an augmented proliferation of corneal epithelial cells and increased local productions of CCL3, CCL12, TNFα, IL-1β, M-CSF, and G-CSF. C1q KO mice reconstituted with WT bone marrow have a normal level of C1q in blood but showed a similarly accelerated wound healing as the control C1q KO mice. Contrarily, WT mice reconstituted with C1q KO bone marrow showed a similar phenotype as the control WT mice. C1q transcripts were detectable in both human and mouse corneal epithelial cells and knocking out C1q in human corneal epithelial cells accelerated the wound healing process in vitro. Moreover, locally knocking down C1q expression via siRNA in cornea significantly accelerated corneal wound healing in vivo.

Conclusions : C1q locally produced in the cornea, but not the C1q systemically produced by the myeloid cells negatively regulates corneal epithelial cell proliferation during wound healing. Corneal epithelial cells produce C1q, and knocking out C1q in human corneal epithelial cells or knocking down C1q in the mouse cornea accelerates corneal healing process. The results revealed a novel role of locally produced C1q in regulating corneal wound healing and suggested C1q as a new therapeutic target for this potentially blinding condition.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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