Expression of inducible nitric oxide synthase in the eye from endotoxin- induced uveitis rats

Inducible nitric oxide (NO) synthase (iNOS) has been implicated in the pathogenesis of endotoxin-induced uveitis (EIU). This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat. EIU was induced in Lewis rats by a single foot pad injection of 150 microgram...

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Veröffentlicht in:Investigative ophthalmology & visual science 1996-05, Vol.37 (6), p.1187-1196
Hauptverfasser: Jacquemin, E, de Kozak, Y, Thillaye, B, Courtois, Y, Goureau, O
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container_issue 6
container_start_page 1187
container_title Investigative ophthalmology & visual science
container_volume 37
creator Jacquemin, E
de Kozak, Y
Thillaye, B
Courtois, Y
Goureau, O
description Inducible nitric oxide (NO) synthase (iNOS) has been implicated in the pathogenesis of endotoxin-induced uveitis (EIU). This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat. EIU was induced in Lewis rats by a single foot pad injection of 150 micrograms lipopolysaccharide (LPS) from Salmonella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS localization by in situ hybridization, and comparison of OX-42- and ED1-positive cell appearance and of glial response by specific immunohistochemistry. iNOS mRNA was not detected in the iris-ciliary body nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in stromal cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours after LPS injection. iNOS-positive cells were also present on the vitreous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- and ED1-positive cells (microglia, macrophages, or polymorphonuclear leukocytes) colocalized in part with some iNOS-positive cells in the ciliary body and in the retina. Furthermore, expression of iNOS in Müller cells cannot be excluded. These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA expression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the eye and the retina are the major source of NO. These results support the hypothesis that both inflammatory and resident ocular cells are involved in iNOS expression during EIU.
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This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat. EIU was induced in Lewis rats by a single foot pad injection of 150 micrograms lipopolysaccharide (LPS) from Salmonella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS localization by in situ hybridization, and comparison of OX-42- and ED1-positive cell appearance and of glial response by specific immunohistochemistry. iNOS mRNA was not detected in the iris-ciliary body nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in stromal cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours after LPS injection. iNOS-positive cells were also present on the vitreous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- and ED1-positive cells (microglia, macrophages, or polymorphonuclear leukocytes) colocalized in part with some iNOS-positive cells in the ciliary body and in the retina. Furthermore, expression of iNOS in Müller cells cannot be excluded. These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA expression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the eye and the retina are the major source of NO. 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This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat. EIU was induced in Lewis rats by a single foot pad injection of 150 micrograms lipopolysaccharide (LPS) from Salmonella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS localization by in situ hybridization, and comparison of OX-42- and ED1-positive cell appearance and of glial response by specific immunohistochemistry. iNOS mRNA was not detected in the iris-ciliary body nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in stromal cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours after LPS injection. iNOS-positive cells were also present on the vitreous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- and ED1-positive cells (microglia, macrophages, or polymorphonuclear leukocytes) colocalized in part with some iNOS-positive cells in the ciliary body and in the retina. Furthermore, expression of iNOS in Müller cells cannot be excluded. These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA expression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the eye and the retina are the major source of NO. These results support the hypothesis that both inflammatory and resident ocular cells are involved in iNOS expression during EIU.</description><subject>Animals</subject><subject>Anterior Eye Segment - enzymology</subject><subject>Anterior Eye Segment - pathology</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Ciliary Body - enzymology</subject><subject>Ciliary Body - pathology</subject><subject>DNA Primers - chemistry</subject><subject>DNA Probes</subject><subject>DNA, Single-Stranded</subject><subject>Enzyme Induction</subject><subject>Eye - enzymology</subject><subject>Eye - pathology</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>In Situ Hybridization</subject><subject>Iris - enzymology</subject><subject>Iris - pathology</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Nitric Oxide Synthase - analysis</subject><subject>Nitric Oxide Synthase - biosynthesis</subject><subject>Ophthalmology</subject><subject>Pigment Epithelium of Eye - enzymology</subject><subject>Pigment Epithelium of Eye - pathology</subject><subject>Rats</subject><subject>Rats, Inbred BN</subject><subject>Rats, Inbred Lew</subject><subject>Retina - enzymology</subject><subject>Retina - pathology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Salmonella typhimurium</subject><subject>Uvea diseases</subject><subject>Uveitis - chemically induced</subject><subject>Uveitis - enzymology</subject><subject>Uveitis - pathology</subject><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9j0tLxDAUhYMo4zj6E4QsxF0hrybpUobxAQNudCkl09zYSJsOSWtn_r2BGbybu_i-c-BcoCUtS1aUSvNLtCRUyIIIIq7RTUo_hDBKGVmghZacSs6X6Gtz2EdIyQ8BDw77YKfG7zrAwY_RN3g4eAs4HcPYmgSZ47EFDEfALg49hmCHMTuhOEXB4ukX_OgTjmZMt-jKmS7B3fmv0Ofz5mP9WmzfX97WT9uiZVKOhRb5nNgRLhiThJdW0FIbIIY5ZXQlRMlVnsG4lMxVthEEKuMcVVaCKhVfoftT737a9WDrffS9icf6PDPzhzM3qTGdiyY0Pv1rnGjFKp21x5PW-u929hHq1Juuy6W0nueZq1rWlGrF_wBgt2kk</recordid><startdate>19960501</startdate><enddate>19960501</enddate><creator>Jacquemin, E</creator><creator>de Kozak, Y</creator><creator>Thillaye, B</creator><creator>Courtois, Y</creator><creator>Goureau, O</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19960501</creationdate><title>Expression of inducible nitric oxide synthase in the eye from endotoxin- induced uveitis rats</title><author>Jacquemin, E ; de Kozak, Y ; Thillaye, B ; Courtois, Y ; Goureau, O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h266t-84444f4b034226035d4158ae0a2f7a894453704023662f9dc40e9aff17d6e7573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Anterior Eye Segment - enzymology</topic><topic>Anterior Eye Segment - pathology</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Ciliary Body - enzymology</topic><topic>Ciliary Body - pathology</topic><topic>DNA Primers - chemistry</topic><topic>DNA Probes</topic><topic>DNA, Single-Stranded</topic><topic>Enzyme Induction</topic><topic>Eye - enzymology</topic><topic>Eye - pathology</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>In Situ Hybridization</topic><topic>Iris - enzymology</topic><topic>Iris - pathology</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Nitric Oxide Synthase - analysis</topic><topic>Nitric Oxide Synthase - biosynthesis</topic><topic>Ophthalmology</topic><topic>Pigment Epithelium of Eye - enzymology</topic><topic>Pigment Epithelium of Eye - pathology</topic><topic>Rats</topic><topic>Rats, Inbred BN</topic><topic>Rats, Inbred Lew</topic><topic>Retina - enzymology</topic><topic>Retina - pathology</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Salmonella typhimurium</topic><topic>Uvea diseases</topic><topic>Uveitis - chemically induced</topic><topic>Uveitis - enzymology</topic><topic>Uveitis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jacquemin, E</creatorcontrib><creatorcontrib>de Kozak, Y</creatorcontrib><creatorcontrib>Thillaye, B</creatorcontrib><creatorcontrib>Courtois, Y</creatorcontrib><creatorcontrib>Goureau, O</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Investigative ophthalmology &amp; visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jacquemin, E</au><au>de Kozak, Y</au><au>Thillaye, B</au><au>Courtois, Y</au><au>Goureau, O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of inducible nitric oxide synthase in the eye from endotoxin- induced uveitis rats</atitle><jtitle>Investigative ophthalmology &amp; visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>1996-05-01</date><risdate>1996</risdate><volume>37</volume><issue>6</issue><spage>1187</spage><epage>1196</epage><pages>1187-1196</pages><issn>0146-0404</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>Inducible nitric oxide (NO) synthase (iNOS) has been implicated in the pathogenesis of endotoxin-induced uveitis (EIU). This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat. EIU was induced in Lewis rats by a single foot pad injection of 150 micrograms lipopolysaccharide (LPS) from Salmonella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS localization by in situ hybridization, and comparison of OX-42- and ED1-positive cell appearance and of glial response by specific immunohistochemistry. iNOS mRNA was not detected in the iris-ciliary body nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in stromal cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours after LPS injection. iNOS-positive cells were also present on the vitreous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- and ED1-positive cells (microglia, macrophages, or polymorphonuclear leukocytes) colocalized in part with some iNOS-positive cells in the ciliary body and in the retina. Furthermore, expression of iNOS in Müller cells cannot be excluded. These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA expression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the eye and the retina are the major source of NO. These results support the hypothesis that both inflammatory and resident ocular cells are involved in iNOS expression during EIU.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>8631633</pmid><tpages>10</tpages></addata></record>
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ispartof Investigative ophthalmology & visual science, 1996-05, Vol.37 (6), p.1187-1196
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recordid cdi_pubmed_primary_8631633
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Anterior Eye Segment - enzymology
Anterior Eye Segment - pathology
Base Sequence
Biological and medical sciences
Ciliary Body - enzymology
Ciliary Body - pathology
DNA Primers - chemistry
DNA Probes
DNA, Single-Stranded
Enzyme Induction
Eye - enzymology
Eye - pathology
Fluorescent Antibody Technique
Gene Expression Regulation, Enzymologic
In Situ Hybridization
Iris - enzymology
Iris - pathology
Lipopolysaccharides
Male
Medical sciences
Molecular Sequence Data
Nitric Oxide Synthase - analysis
Nitric Oxide Synthase - biosynthesis
Ophthalmology
Pigment Epithelium of Eye - enzymology
Pigment Epithelium of Eye - pathology
Rats
Rats, Inbred BN
Rats, Inbred Lew
Retina - enzymology
Retina - pathology
RNA, Messenger - biosynthesis
Salmonella typhimurium
Uvea diseases
Uveitis - chemically induced
Uveitis - enzymology
Uveitis - pathology
title Expression of inducible nitric oxide synthase in the eye from endotoxin- induced uveitis rats
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