June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Anti-inflammatory and anti-fibrotic effects of calcitonin gene-related peptide on corneal wound healing
Author Affiliations & Notes
  • Asmaa Zidan
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Shuyan Zhu
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Kunpeng Pang
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Elsayed Elbasiony
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Sheyda Najafi
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Jia Yin
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Asmaa Zidan None; Shuyan Zhu None; Kunpeng Pang None; Elsayed Elbasiony None; Sheyda Najafi None; Jia Yin Claris Biotherapeutics, Code C (Consultant/Contractor), Kera Therapeutics, Code O (Owner)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3124. doi:
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      Asmaa Zidan, Shuyan Zhu, Kunpeng Pang, Elsayed Elbasiony, Sheyda Najafi, Jia Yin; Anti-inflammatory and anti-fibrotic effects of calcitonin gene-related peptide on corneal wound healing. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3124.

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

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Abstract

Purpose : Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide abundantly expressed by corneal nerves. In this study, we aim to examine the effects of CGRP on corneal wound healing, inflammation, and opacity after mechanical injury in mice.

Methods : Corneal injury was induced in C57BL/6 mice by removing the epithelium and anterior one-third of the stroma using a hand-held Alger brush II. Following injury, mice were topically treated either with CGRP 50µm or PBS control three time daily for 14 days. Corneal epithelial healing, stromal opacity, and thickness were examined using slit lamp photography and OCT. Corneal sensitivity was assessed with a Cochet-Bonnet esthesiometer. Leukocyte infiltration was determined using flow cytometry, and TNFα and IL1β expression was measured by RT-qPCR. Histological analysis of the tissues was performed with H&E staining. Corneal alpha-smooth muscle actin (αSMA) and TGFβ-1 expression was assessed with immunostaining.

Results : Topical CGRP treatment accelerated epithelial wound closure with 16.5±7.9% remaining wound area at 48 hrs after injury, compared to 48.9±9.4% in control group (P=0.02). CGRP treatment reduced corneal opacity (opacity score 0.8±0.2 vs 2.4±0.3 in control, P=0.005) and central corneal thickness (85.2±1µm vs 159.7±29.2µm in control, P=0.01) after 14 days. Corneal sensitivity in CGRP-treated mice recovered more rapidly after injury (3.5±0.2cm vs 2.2±0.1cm in control, P=0.009). At day 3, CGRP treatment reduced CD45+ cell infiltration into the cornea (6.1±0.3% vs 10.2±1.2% in control, P=0.03) and TNFα and IL1β expression by 33.6±1.4% and 54.3±15.8 %, respectively (P=0.04). H&E staining showed decreased stromal fibrosis and preserved tissue integrity in CGRP-treated corneas. Corneal stromal αSMA and TGFβ-1 immunostaining was decreased with CGRP treatment.

Conclusions : Following corneal injury, topical CGRP application accelerates epithelial wound closure, reduces corneal opacity and edema, and restores corneal sensitivity. CGRP may promote corneal wound healing via reducing leukocyte infiltration and inflammatory cytokine production, as well as dampening TGFβ-1-mediated tissue fibrosis.

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

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