The role of neutrophils in corneal nerve regeneration

Abstract Background To investigate the role of neutrophils in corneal nerve regeneration. Methods A mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ri...

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Main Authors: Xiaowen Zhao, Minghong Zhang, Fengjiao Li, Cuiping Ma, Dianqiang Wang, Ye Wang
Format: Article
Language:English
Published: BMC 2023-07-01
Series:BMC Ophthalmology
Subjects:
Online Access:https://doi.org/10.1186/s12886-023-03088-9
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author Xiaowen Zhao
Minghong Zhang
Fengjiao Li
Cuiping Ma
Dianqiang Wang
Ye Wang
author_facet Xiaowen Zhao
Minghong Zhang
Fengjiao Li
Cuiping Ma
Dianqiang Wang
Ye Wang
author_sort Xiaowen Zhao
collection DOAJ
description Abstract Background To investigate the role of neutrophils in corneal nerve regeneration. Methods A mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ribonucleic acid sequencing, and bioinformatics. Differential expression analysis was used to perform enrichment analysis to identify any significant differences between these two groups. The differential genes were then intersected with neutrophil-associated genes and a protein-protein interaction network was constructed using the intersected genes. The immune infiltration between the two groups was examined along with the immune cell variation between the high and low gene expression groups. Results Neutrophil removal delays corneal epithelial and nerve regeneration. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both sets were obtained. Molecular Complex Detection analysis yielded five key genes, namely integrin subunit beta 2 (ITGB2), matrix metallopeptidase 9 (MMP9), epidermal growth factor (EGF), serpin family E member 1 (SERPINE1), and plasminogen activator urokinase receptor (PLAUR). Among these genes, ITGB2, SERPINE1, and PLAUR exhibited increased expression in the neutrophil-confined group, while MMP9 and EGF showed decreased expression, with MMP9 and EGF displaying a more significant difference. Immune infiltration was also observed between the two groups, revealing significant differences in the infiltration of M0 macrophages, activated mast cells, and neutrophils. Moreover, the neutrophil levels were lower in the groups with low MMP9 and EGF expressions and higher in the high-expression group. Conclusion Neutrophil confinement might significantly affect the MMP9 and EGF expression levels. Strategies to inhibit MMP9 could potentially yield therapeutic benefits.
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spelling doaj.art-ba2340bbb2ae4c94afe318c99fe07dd92023-07-30T11:10:21ZengBMCBMC Ophthalmology1471-24152023-07-0123111210.1186/s12886-023-03088-9The role of neutrophils in corneal nerve regenerationXiaowen Zhao0Minghong Zhang1Fengjiao Li2Cuiping Ma3Dianqiang Wang4Ye Wang5Core Laboratory, The Affiliated Qingdao Central Hospital of Qingdao UniversityQingdao Aier Eye HospitalDepartment of Opthalmology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityShandong Provincial Key Laboratory of Biochemical Engineering, Qingdao Nucleic Acid Rapid Detection Engineering Research Center, College of Marine Science and Biological Engineering, Qingdao University of Science and TechnologyQingdao Aier Eye HospitalCore Laboratory, The Affiliated Qingdao Central Hospital of Qingdao UniversityAbstract Background To investigate the role of neutrophils in corneal nerve regeneration. Methods A mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ribonucleic acid sequencing, and bioinformatics. Differential expression analysis was used to perform enrichment analysis to identify any significant differences between these two groups. The differential genes were then intersected with neutrophil-associated genes and a protein-protein interaction network was constructed using the intersected genes. The immune infiltration between the two groups was examined along with the immune cell variation between the high and low gene expression groups. Results Neutrophil removal delays corneal epithelial and nerve regeneration. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both sets were obtained. Molecular Complex Detection analysis yielded five key genes, namely integrin subunit beta 2 (ITGB2), matrix metallopeptidase 9 (MMP9), epidermal growth factor (EGF), serpin family E member 1 (SERPINE1), and plasminogen activator urokinase receptor (PLAUR). Among these genes, ITGB2, SERPINE1, and PLAUR exhibited increased expression in the neutrophil-confined group, while MMP9 and EGF showed decreased expression, with MMP9 and EGF displaying a more significant difference. Immune infiltration was also observed between the two groups, revealing significant differences in the infiltration of M0 macrophages, activated mast cells, and neutrophils. Moreover, the neutrophil levels were lower in the groups with low MMP9 and EGF expressions and higher in the high-expression group. Conclusion Neutrophil confinement might significantly affect the MMP9 and EGF expression levels. Strategies to inhibit MMP9 could potentially yield therapeutic benefits.https://doi.org/10.1186/s12886-023-03088-9Corneal nerveCorneal scrapingNeutrophilsMMP9EGF
spellingShingle Xiaowen Zhao
Minghong Zhang
Fengjiao Li
Cuiping Ma
Dianqiang Wang
Ye Wang
The role of neutrophils in corneal nerve regeneration
BMC Ophthalmology
Corneal nerve
Corneal scraping
Neutrophils
MMP9
EGF
title The role of neutrophils in corneal nerve regeneration
title_full The role of neutrophils in corneal nerve regeneration
title_fullStr The role of neutrophils in corneal nerve regeneration
title_full_unstemmed The role of neutrophils in corneal nerve regeneration
title_short The role of neutrophils in corneal nerve regeneration
title_sort role of neutrophils in corneal nerve regeneration
topic Corneal nerve
Corneal scraping
Neutrophils
MMP9
EGF
url https://doi.org/10.1186/s12886-023-03088-9
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