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Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis

PURPOSE: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis. METHODS: A mouse model of major histocompatibility-match...

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Autores principales: Shamloo, Kiumars, Weng, Judy, Ross, Christopher, Lee, Jenni, Alfuraih, Saleh, Totonchy, Jennifer, Sharma, Ajay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525838/
https://www.ncbi.nlm.nih.gov/pubmed/34643664
http://dx.doi.org/10.1167/iovs.62.13.10
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author Shamloo, Kiumars
Weng, Judy
Ross, Christopher
Lee, Jenni
Alfuraih, Saleh
Totonchy, Jennifer
Sharma, Ajay
author_facet Shamloo, Kiumars
Weng, Judy
Ross, Christopher
Lee, Jenni
Alfuraih, Saleh
Totonchy, Jennifer
Sharma, Ajay
author_sort Shamloo, Kiumars
collection PubMed
description PURPOSE: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis. METHODS: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. Eyes were harvested at 4 and 8 weeks after the transplant for alpha-smooth muscle actin (α-SMA), angiotensinogen, and angiotensin-converting enzyme (ACE) immunostaining. Conjunctiva was harvested for gene expression quantification of α-SMA, angiotensinogen, and ACE. RESULTS: More than 80% of the spleen cells in the recipient mice were chromosome Y positive, thus conforming successful engraftment. A significant decrease in tear secretion and a marked increase in corneal keratopathy score after allogeneic transplantation indicated the onset of ocular GVHD in these mice. A significant increase in α-SMA gene expression and the presence of a large number of α-SMA–positive cells was noted in the bulbar orbital conjunctiva of mice after allogeneic transplantation. Allogenic transplantation also caused a significant increase in the gene expression and protein expression of angiotensinogen and ACE in the subconjunctival eyelid area. CONCLUSIONS: Results of the present study demonstrate that GVHD-associated conjunctival fibrosis is accompanied by myofibroblast formation and activation of the local conjunctival RAS.
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spelling pubmed-85258382021-10-28 Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis Shamloo, Kiumars Weng, Judy Ross, Christopher Lee, Jenni Alfuraih, Saleh Totonchy, Jennifer Sharma, Ajay Invest Ophthalmol Vis Sci Cornea PURPOSE: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis. METHODS: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. Eyes were harvested at 4 and 8 weeks after the transplant for alpha-smooth muscle actin (α-SMA), angiotensinogen, and angiotensin-converting enzyme (ACE) immunostaining. Conjunctiva was harvested for gene expression quantification of α-SMA, angiotensinogen, and ACE. RESULTS: More than 80% of the spleen cells in the recipient mice were chromosome Y positive, thus conforming successful engraftment. A significant decrease in tear secretion and a marked increase in corneal keratopathy score after allogeneic transplantation indicated the onset of ocular GVHD in these mice. A significant increase in α-SMA gene expression and the presence of a large number of α-SMA–positive cells was noted in the bulbar orbital conjunctiva of mice after allogeneic transplantation. Allogenic transplantation also caused a significant increase in the gene expression and protein expression of angiotensinogen and ACE in the subconjunctival eyelid area. CONCLUSIONS: Results of the present study demonstrate that GVHD-associated conjunctival fibrosis is accompanied by myofibroblast formation and activation of the local conjunctival RAS. The Association for Research in Vision and Ophthalmology 2021-10-13 /pmc/articles/PMC8525838/ /pubmed/34643664 http://dx.doi.org/10.1167/iovs.62.13.10 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License.
spellingShingle Cornea
Shamloo, Kiumars
Weng, Judy
Ross, Christopher
Lee, Jenni
Alfuraih, Saleh
Totonchy, Jennifer
Sharma, Ajay
Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis
title Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis
title_full Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis
title_fullStr Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis
title_full_unstemmed Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis
title_short Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis
title_sort local renin-angiotensin system activation and myofibroblast formation in graft versus host disease–associated conjunctival fibrosis
topic Cornea
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525838/
https://www.ncbi.nlm.nih.gov/pubmed/34643664
http://dx.doi.org/10.1167/iovs.62.13.10
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