Cargando…

Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry

Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveit...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Jing, Wu, Jiangmei, Lu, Daqian, To, Chi-Ho, Lam, Thomas Chuen, Lin, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223489/
https://www.ncbi.nlm.nih.gov/pubmed/35742911
http://dx.doi.org/10.3390/ijms23126464
_version_ 1784733136206168064
author Zhang, Jing
Wu, Jiangmei
Lu, Daqian
To, Chi-Ho
Lam, Thomas Chuen
Lin, Bin
author_facet Zhang, Jing
Wu, Jiangmei
Lu, Daqian
To, Chi-Ho
Lam, Thomas Chuen
Lin, Bin
author_sort Zhang, Jing
collection PubMed
description Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveitis and associated acute retinal inflammation. To understand the pathogenic mechanism of uveitis and screen potential targets for treatment, we analyzed the retinal proteomic profile of the EIU mouse model using a data-independent acquisition-based mass spectrometry (SWATH-MS). After systemic LPS administration, we observed activation of microglial cells accompanied with the elevation of pro-inflammatory mediators and visual function declines. In total, we observed 79 upregulated and 90 downregulated differentially expressed proteins (DEPs). Among the DEPs, we found that histone family members (histone H1, H2A, H2B) and blood proteins including haptoglobin (HP), hemopexin (HPX), and fibrinogen gamma chain (FGG) were dramatically increased in EIU groups relative to those in control groups. We identified phototransduction and synaptic vesicle cycle as the top two significant KEGG pathways. Moreover, canonical pathway analysis on DEPs using Ingenuity Pathway Analysis revealed top three most significant enriched pathways related to acute phase response signaling, synaptogenesis signaling, and eif2 signaling. We further confirmed upregulation of several DEPs associated with the acute phase response signaling including HP, HPX, and FGG in LPS-treated retinas by qPCR and Western blot. In summary, this study serves as the first report to detect retinal proteome changes in the EIU model. The study provides several potential candidates for exploring the mechanism and novel therapeutic targets for uveitis and other retinal inflammatory diseases.
format Online
Article
Text
id pubmed-9223489
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92234892022-06-24 Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry Zhang, Jing Wu, Jiangmei Lu, Daqian To, Chi-Ho Lam, Thomas Chuen Lin, Bin Int J Mol Sci Article Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveitis and associated acute retinal inflammation. To understand the pathogenic mechanism of uveitis and screen potential targets for treatment, we analyzed the retinal proteomic profile of the EIU mouse model using a data-independent acquisition-based mass spectrometry (SWATH-MS). After systemic LPS administration, we observed activation of microglial cells accompanied with the elevation of pro-inflammatory mediators and visual function declines. In total, we observed 79 upregulated and 90 downregulated differentially expressed proteins (DEPs). Among the DEPs, we found that histone family members (histone H1, H2A, H2B) and blood proteins including haptoglobin (HP), hemopexin (HPX), and fibrinogen gamma chain (FGG) were dramatically increased in EIU groups relative to those in control groups. We identified phototransduction and synaptic vesicle cycle as the top two significant KEGG pathways. Moreover, canonical pathway analysis on DEPs using Ingenuity Pathway Analysis revealed top three most significant enriched pathways related to acute phase response signaling, synaptogenesis signaling, and eif2 signaling. We further confirmed upregulation of several DEPs associated with the acute phase response signaling including HP, HPX, and FGG in LPS-treated retinas by qPCR and Western blot. In summary, this study serves as the first report to detect retinal proteome changes in the EIU model. The study provides several potential candidates for exploring the mechanism and novel therapeutic targets for uveitis and other retinal inflammatory diseases. MDPI 2022-06-09 /pmc/articles/PMC9223489/ /pubmed/35742911 http://dx.doi.org/10.3390/ijms23126464 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Jing
Wu, Jiangmei
Lu, Daqian
To, Chi-Ho
Lam, Thomas Chuen
Lin, Bin
Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
title Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
title_full Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
title_fullStr Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
title_full_unstemmed Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
title_short Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
title_sort retinal proteomic analysis in a mouse model of endotoxin-induced uveitis using data-independent acquisition-based mass spectrometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223489/
https://www.ncbi.nlm.nih.gov/pubmed/35742911
http://dx.doi.org/10.3390/ijms23126464
work_keys_str_mv AT zhangjing retinalproteomicanalysisinamousemodelofendotoxininduceduveitisusingdataindependentacquisitionbasedmassspectrometry
AT wujiangmei retinalproteomicanalysisinamousemodelofendotoxininduceduveitisusingdataindependentacquisitionbasedmassspectrometry
AT ludaqian retinalproteomicanalysisinamousemodelofendotoxininduceduveitisusingdataindependentacquisitionbasedmassspectrometry
AT tochiho retinalproteomicanalysisinamousemodelofendotoxininduceduveitisusingdataindependentacquisitionbasedmassspectrometry
AT lamthomaschuen retinalproteomicanalysisinamousemodelofendotoxininduceduveitisusingdataindependentacquisitionbasedmassspectrometry
AT linbin retinalproteomicanalysisinamousemodelofendotoxininduceduveitisusingdataindependentacquisitionbasedmassspectrometry