Angiotensin II and Its Receptor Subtypes in the Human Retina

To quantify and evaluate the distribution of angiotensin II (Ang II) and its receptors in the human retina. Donor eyes were obtained within 12 hours postmortem and classified as hypertensive or normotensive and diabetic or nondiabetic, based on the donors' medical histories. Ang II in retina an...

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Veröffentlicht in:Investigative ophthalmology & visual science 2007-07, Vol.48 (7), p.3301-3311
Hauptverfasser: Senanayake, Preenie deS, Drazba, Judy, Shadrach, Karen, Milsted, Amy, Rungger-Brandle, Elisabeth, Nishiyama, Kazutoshi, Miura, Shin-Ichiro, Karnik, Sadashiva, Sears, Jonathan E, Hollyfield, Joe G
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container_end_page 3311
container_issue 7
container_start_page 3301
container_title Investigative ophthalmology & visual science
container_volume 48
creator Senanayake, Preenie deS
Drazba, Judy
Shadrach, Karen
Milsted, Amy
Rungger-Brandle, Elisabeth
Nishiyama, Kazutoshi
Miura, Shin-Ichiro
Karnik, Sadashiva
Sears, Jonathan E
Hollyfield, Joe G
description To quantify and evaluate the distribution of angiotensin II (Ang II) and its receptors in the human retina. Donor eyes were obtained within 12 hours postmortem and classified as hypertensive or normotensive and diabetic or nondiabetic, based on the donors' medical histories. Ang II in retina and vitreous was quantified by RIA. Ang II receptors were characterized and quantified by competitive membrane-binding assays. Ang II, its heptapeptide metabolite Ang-(1-7), and AT1 and AT2 receptors were localized by immunohistochemistry and confocal imaging. Levels of Ang II in the retina were significantly higher than in vitreous (P < 0.05). Ang II in the diabetic retina had a higher median compared with that in the nondiabetic retina. Ang II and Ang-(1-7) colocalized in retinal Müller cells. The retina had the highest levels of Ang II receptors that were significantly higher than the optic nerve, retinal pigment epithelium-choroid complex, and ciliary body-iris complex (P < 0.05). AT1 receptors were more abundant than AT2 receptors in the retina. Immunoreactivity for AT1 was detected in Müller cells and on blood vessels. AT2 receptors were localized throughout the Müller cells and nuclei of ganglion cells and neurons in the inner nuclear layer. In the human retina, identification of Ang II and its bioactive metabolite Ang-(1-7) in Müller cells suggests that these glial cells are able to produce and process Ang II. Ang receptors were localized in the blood vessels and neural cells. Local Ang II signaling may thus allow for autoregulation of neurovascular activity. Such an autonomous system could modulate the onset and severity of retinovascular disease.
doi_str_mv 10.1167/iovs.06-1024
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Donor eyes were obtained within 12 hours postmortem and classified as hypertensive or normotensive and diabetic or nondiabetic, based on the donors' medical histories. Ang II in retina and vitreous was quantified by RIA. Ang II receptors were characterized and quantified by competitive membrane-binding assays. Ang II, its heptapeptide metabolite Ang-(1-7), and AT1 and AT2 receptors were localized by immunohistochemistry and confocal imaging. Levels of Ang II in the retina were significantly higher than in vitreous (P &lt; 0.05). Ang II in the diabetic retina had a higher median compared with that in the nondiabetic retina. Ang II and Ang-(1-7) colocalized in retinal Müller cells. The retina had the highest levels of Ang II receptors that were significantly higher than the optic nerve, retinal pigment epithelium-choroid complex, and ciliary body-iris complex (P &lt; 0.05). AT1 receptors were more abundant than AT2 receptors in the retina. Immunoreactivity for AT1 was detected in Müller cells and on blood vessels. AT2 receptors were localized throughout the Müller cells and nuclei of ganglion cells and neurons in the inner nuclear layer. In the human retina, identification of Ang II and its bioactive metabolite Ang-(1-7) in Müller cells suggests that these glial cells are able to produce and process Ang II. Ang receptors were localized in the blood vessels and neural cells. Local Ang II signaling may thus allow for autoregulation of neurovascular activity. Such an autonomous system could modulate the onset and severity of retinovascular disease.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.06-1024</identifier><identifier>PMID: 17591902</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Angiotensin I - metabolism ; Angiotensin II - metabolism ; Binding, Competitive ; Biological and medical sciences ; Blotting, Western ; Eye and associated structures. Visual pathways and centers. Vision ; Female ; Fluorescent Antibody Technique, Indirect ; Fundamental and applied biological sciences. Psychology ; Humans ; Male ; Microscopy, Confocal ; Middle Aged ; Peptide Fragments - metabolism ; Peptidyl-Dipeptidase A - metabolism ; Radioimmunoassay ; Receptor, Angiotensin, Type 1 - metabolism ; Receptor, Angiotensin, Type 2 - metabolism ; Retina - metabolism ; Tissue Donors ; Vertebrates: nervous system and sense organs</subject><ispartof>Investigative ophthalmology &amp; visual science, 2007-07, Vol.48 (7), p.3301-3311</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-c6d3f7b3ab6ebdd76fc2cf926fd3ad04b3801cbf8c93995dd054b5574392cc303</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=18897687$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17591902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Senanayake, Preenie deS</creatorcontrib><creatorcontrib>Drazba, Judy</creatorcontrib><creatorcontrib>Shadrach, Karen</creatorcontrib><creatorcontrib>Milsted, Amy</creatorcontrib><creatorcontrib>Rungger-Brandle, Elisabeth</creatorcontrib><creatorcontrib>Nishiyama, Kazutoshi</creatorcontrib><creatorcontrib>Miura, Shin-Ichiro</creatorcontrib><creatorcontrib>Karnik, Sadashiva</creatorcontrib><creatorcontrib>Sears, Jonathan E</creatorcontrib><creatorcontrib>Hollyfield, Joe G</creatorcontrib><title>Angiotensin II and Its Receptor Subtypes in the Human Retina</title><title>Investigative ophthalmology &amp; visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To quantify and evaluate the distribution of angiotensin II (Ang II) and its receptors in the human retina. 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Vision</subject><subject>Female</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Male</subject><subject>Microscopy, Confocal</subject><subject>Middle Aged</subject><subject>Peptide Fragments - metabolism</subject><subject>Peptidyl-Dipeptidase A - metabolism</subject><subject>Radioimmunoassay</subject><subject>Receptor, Angiotensin, Type 1 - metabolism</subject><subject>Receptor, Angiotensin, Type 2 - metabolism</subject><subject>Retina - metabolism</subject><subject>Tissue Donors</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1LwzAYh4Mobk5vnqUXPdn55qNJA17GUFcYCH6cQ5qkW6Qfs2kd--_t2GCn9_B7eHh5ELrFMMWYiyff_IUp8BgDYWdojJOExIlI6TkaA2Y8BgZshK5C-AEgGBO4RCMsEoklkDF6ntUr33SuDr6OsizStY2yLkQfzrhN17TRZ593u40L0bB3axct-krXw9z5Wl-ji0KXwd0c7wR9v758zRfx8v0tm8-WsWGYd7HhlhYipzrnLrdW8MIQU0jCC0u1BZbTFLDJi9RIKmViLSQsTxLBqCTGUKAT9HDwbtrmt3ehU5UPxpWlrl3TByWAc8KlHMDHA2jaJoTWFWrT-kq3O4VB7WupfS0FXO1rDfjd0dvnlbMn-JhnAO6PgA5Gl0Wra-PDiUtTKXgqTg-u_Wq99a1TodJlOWix2m63LFVCUQqY_gMG-H9O</recordid><startdate>20070701</startdate><enddate>20070701</enddate><creator>Senanayake, Preenie deS</creator><creator>Drazba, Judy</creator><creator>Shadrach, Karen</creator><creator>Milsted, Amy</creator><creator>Rungger-Brandle, Elisabeth</creator><creator>Nishiyama, Kazutoshi</creator><creator>Miura, Shin-Ichiro</creator><creator>Karnik, Sadashiva</creator><creator>Sears, Jonathan E</creator><creator>Hollyfield, Joe G</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><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20070701</creationdate><title>Angiotensin II and Its Receptor Subtypes in the Human Retina</title><author>Senanayake, Preenie deS ; Drazba, Judy ; Shadrach, Karen ; Milsted, Amy ; Rungger-Brandle, Elisabeth ; Nishiyama, Kazutoshi ; Miura, Shin-Ichiro ; Karnik, Sadashiva ; Sears, Jonathan E ; Hollyfield, Joe G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-c6d3f7b3ab6ebdd76fc2cf926fd3ad04b3801cbf8c93995dd054b5574392cc303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angiotensin I - metabolism</topic><topic>Angiotensin II - metabolism</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Female</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Male</topic><topic>Microscopy, Confocal</topic><topic>Middle Aged</topic><topic>Peptide Fragments - metabolism</topic><topic>Peptidyl-Dipeptidase A - metabolism</topic><topic>Radioimmunoassay</topic><topic>Receptor, Angiotensin, Type 1 - metabolism</topic><topic>Receptor, Angiotensin, Type 2 - metabolism</topic><topic>Retina - metabolism</topic><topic>Tissue Donors</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Senanayake, Preenie deS</creatorcontrib><creatorcontrib>Drazba, Judy</creatorcontrib><creatorcontrib>Shadrach, Karen</creatorcontrib><creatorcontrib>Milsted, Amy</creatorcontrib><creatorcontrib>Rungger-Brandle, Elisabeth</creatorcontrib><creatorcontrib>Nishiyama, Kazutoshi</creatorcontrib><creatorcontrib>Miura, Shin-Ichiro</creatorcontrib><creatorcontrib>Karnik, Sadashiva</creatorcontrib><creatorcontrib>Sears, Jonathan E</creatorcontrib><creatorcontrib>Hollyfield, Joe G</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology &amp; visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Senanayake, Preenie deS</au><au>Drazba, Judy</au><au>Shadrach, Karen</au><au>Milsted, Amy</au><au>Rungger-Brandle, Elisabeth</au><au>Nishiyama, Kazutoshi</au><au>Miura, Shin-Ichiro</au><au>Karnik, Sadashiva</au><au>Sears, Jonathan E</au><au>Hollyfield, Joe G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiotensin II and Its Receptor Subtypes in the Human Retina</atitle><jtitle>Investigative ophthalmology &amp; visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>48</volume><issue>7</issue><spage>3301</spage><epage>3311</epage><pages>3301-3311</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To quantify and evaluate the distribution of angiotensin II (Ang II) and its receptors in the human retina. Donor eyes were obtained within 12 hours postmortem and classified as hypertensive or normotensive and diabetic or nondiabetic, based on the donors' medical histories. Ang II in retina and vitreous was quantified by RIA. Ang II receptors were characterized and quantified by competitive membrane-binding assays. Ang II, its heptapeptide metabolite Ang-(1-7), and AT1 and AT2 receptors were localized by immunohistochemistry and confocal imaging. Levels of Ang II in the retina were significantly higher than in vitreous (P &lt; 0.05). Ang II in the diabetic retina had a higher median compared with that in the nondiabetic retina. Ang II and Ang-(1-7) colocalized in retinal Müller cells. The retina had the highest levels of Ang II receptors that were significantly higher than the optic nerve, retinal pigment epithelium-choroid complex, and ciliary body-iris complex (P &lt; 0.05). AT1 receptors were more abundant than AT2 receptors in the retina. Immunoreactivity for AT1 was detected in Müller cells and on blood vessels. AT2 receptors were localized throughout the Müller cells and nuclei of ganglion cells and neurons in the inner nuclear layer. In the human retina, identification of Ang II and its bioactive metabolite Ang-(1-7) in Müller cells suggests that these glial cells are able to produce and process Ang II. Ang receptors were localized in the blood vessels and neural cells. Local Ang II signaling may thus allow for autoregulation of neurovascular activity. Such an autonomous system could modulate the onset and severity of retinovascular disease.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>17591902</pmid><doi>10.1167/iovs.06-1024</doi><tpages>11</tpages></addata></record>
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identifier ISSN: 0146-0404
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subjects Adult
Aged
Aged, 80 and over
Angiotensin I - metabolism
Angiotensin II - metabolism
Binding, Competitive
Biological and medical sciences
Blotting, Western
Eye and associated structures. Visual pathways and centers. Vision
Female
Fluorescent Antibody Technique, Indirect
Fundamental and applied biological sciences. Psychology
Humans
Male
Microscopy, Confocal
Middle Aged
Peptide Fragments - metabolism
Peptidyl-Dipeptidase A - metabolism
Radioimmunoassay
Receptor, Angiotensin, Type 1 - metabolism
Receptor, Angiotensin, Type 2 - metabolism
Retina - metabolism
Tissue Donors
Vertebrates: nervous system and sense organs
title Angiotensin II and Its Receptor Subtypes in the Human Retina
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