June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Characterization of mechanisms underlying ocular GVHD-associated conjunctival fibrosis
Author Affiliations & Notes
  • Alyanna Corpuz
    Chapman University School of Pharmacy, Irvine, California, United States
  • Kiumars Shamloo
    Chapman University School of Pharmacy, Irvine, California, United States
  • Judy Weng
    Chapman University School of Pharmacy, Irvine, California, United States
  • Ajay Sharma
    Chapman University School of Pharmacy, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Alyanna Corpuz None; Kiumars Shamloo None; Judy Weng None; Ajay Sharma None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3990 – A0270. doi:
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    • Get Citation

      Alyanna Corpuz, Kiumars Shamloo, Judy Weng, Ajay Sharma; Characterization of mechanisms underlying ocular GVHD-associated conjunctival fibrosis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3990 – A0270.

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

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Abstract

Purpose : A significant number of chronic GVHD patients suffer from pathological changes affecting conjunctiva including pseudomembranous conjunctivitis, symblepharon, fornix shortening and bulbar subepithelial conjunctival fibrosis. The purpose of the present study was to investigate the mechanisms underlying GVHD-associated conjunctival fibrosis.

Methods : A mouse model of major histocompatibility-matched and minor histocompatibility-mismatched allogeneic transplantation from B10.D2 donors to BALB/c recipients was used to induce ocular GVHD. Control group was BALB/c to BALB/c syngeneic transplantation. Eyes were harvested at 2 and 4 weeks after the transplant. The tissue sections were stained for alpha-smooth muscle actin (α-SMA) to detect myofibroblast formation as a marker for fibrosis. Nanostring technology based spatial immunostaining was performed for macrophages markers. Gene expression quantification and immunostaining was also performed for profibrotic mediators including TGF-β1, PDGF, and components of renin angiotensin system (RAS).

Results : Prominent α-SMA staining was observed in the bulbar orbital conjunctiva of mice that received allogeneic bone marrow transplantation. Immunophenotyping revealed a concomitant increase in macrophage markers and profibrotic M2 macrophage markers in the conjunctiva of these mice. Allogenic transplantation also caused a 2- to 10-fold increase in the gene expression and protein expression of TGF-β1, PDGF, angiotensinogen and angiotensin converting enzyme in the conjunctiva of these mice.

Conclusions : Results of the present study demonstrate that GVHD-associated conjunctival fibrosis is accompanied by myofibroblast formation, influx of macrophages and an increase in profibrotic mediators.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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