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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Role of Angiopoietin-2 in Corneal Lymphangiogenesis</title>
<author><name sortKey="Yuen, Don" sort="Yuen, Don" uniqKey="Yuen D" first="Don" last="Yuen">Don Yuen</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Grimaldo, Sammy" sort="Grimaldo, Sammy" uniqKey="Grimaldo S" first="Sammy" last="Grimaldo">Sammy Grimaldo</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sessa, Roberto" sort="Sessa, Roberto" uniqKey="Sessa R" first="Roberto" last="Sessa">Roberto Sessa</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Truong, Tan" sort="Truong, Tan" uniqKey="Truong T" first="Tan" last="Truong">Tan Truong</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Graduate Group in Vision Science, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Eric" sort="Huang, Eric" uniqKey="Huang E" first="Eric" last="Huang">Eric Huang</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bernas, Michael" sort="Bernas, Michael" uniqKey="Bernas M" first="Michael" last="Bernas">Michael Bernas</name>
<affiliation><nlm:aff id="aff3">Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Daley, Sarah" sort="Daley, Sarah" uniqKey="Daley S" first="Sarah" last="Daley">Sarah Daley</name>
<affiliation><nlm:aff id="aff3">Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Witte, Marlys" sort="Witte, Marlys" uniqKey="Witte M" first="Marlys" last="Witte">Marlys Witte</name>
<affiliation><nlm:aff id="aff3">Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Graduate Group in Vision Science, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24781940</idno>
<idno type="pmc">4039380</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039380</idno>
<idno type="RBID">PMC:4039380</idno>
<idno type="doi">10.1167/iovs.13-13779</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">002E71</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E71</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Role of Angiopoietin-2 in Corneal Lymphangiogenesis</title>
<author><name sortKey="Yuen, Don" sort="Yuen, Don" uniqKey="Yuen D" first="Don" last="Yuen">Don Yuen</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Grimaldo, Sammy" sort="Grimaldo, Sammy" uniqKey="Grimaldo S" first="Sammy" last="Grimaldo">Sammy Grimaldo</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sessa, Roberto" sort="Sessa, Roberto" uniqKey="Sessa R" first="Roberto" last="Sessa">Roberto Sessa</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ecoiffier, Tatiana" sort="Ecoiffier, Tatiana" uniqKey="Ecoiffier T" first="Tatiana" last="Ecoiffier">Tatiana Ecoiffier</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Truong, Tan" sort="Truong, Tan" uniqKey="Truong T" first="Tan" last="Truong">Tan Truong</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Graduate Group in Vision Science, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Eric" sort="Huang, Eric" uniqKey="Huang E" first="Eric" last="Huang">Eric Huang</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bernas, Michael" sort="Bernas, Michael" uniqKey="Bernas M" first="Michael" last="Bernas">Michael Bernas</name>
<affiliation><nlm:aff id="aff3">Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Daley, Sarah" sort="Daley, Sarah" uniqKey="Daley S" first="Sarah" last="Daley">Sarah Daley</name>
<affiliation><nlm:aff id="aff3">Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Witte, Marlys" sort="Witte, Marlys" uniqKey="Witte M" first="Marlys" last="Witte">Marlys Witte</name>
<affiliation><nlm:aff id="aff3">Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name>
<affiliation><nlm:aff id="aff1">Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Graduate Group in Vision Science, University of California, Berkeley, Berkeley, California, United States</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Investigative Ophthalmology & Visual Science</title>
<idno type="ISSN">0146-0404</idno>
<idno type="eISSN">1552-5783</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="st1"><title>Purpose.</title>
<p>Lymphatic research has progressed rapidly in recent years. Lymphatic dysfunction has been found in myriad disorders from cancer metastasis to transplant rejection; however, effective treatment for lymphatic disorders is still limited. This study investigates the role of angiopoietin-2 (Ang-2) in corneal inflammatory lymphangiogenesis (LG) in vivo and in lymphatic endothelial cell (LEC) functions in vitro.</p>
</sec>
<sec id="st2"><title>Methods.</title>
<p>Standard suture placement model was used to study Ang-2 expression in inflamed cornea, and corneal LG and hemangiogenesis (HG) responses in Ang-2 knockout mice. Moreover, human LEC culture system was used to examine the effect of Ang-2 gene knockdown on LEC functions using small interfering RNAs (siRNAs). The effect of siRNA treatment on corneal LG was also assessed in vivo.</p>
</sec>
<sec id="st3"><title>Results.</title>
<p>Angiopoietin-2 was expressed on lymphatic vessels and macrophages in inflamed cornea. While corneal LG response was abolished in Ang-2 knockout mice, the HG response was also significantly suppressed with disorganized patterning. Moreover, anti-Ang-2 treatment inhibited LEC proliferation and capillary tube formation in vitro and corneal LG in vivo.</p>
</sec>
<sec id="st4"><title>Conclusions.</title>
<p>Angiopoietin-2 is critically involved in lymphatic processes in vivo and in vitro. Further investigation of the Ang-2 pathway may provide novel insights and therapeutic strategies for lymphatic-related disorders, which occur both inside and outside the eye.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Invest Ophthalmol Vis Sci</journal-id>
<journal-id journal-id-type="iso-abbrev">Invest. Ophthalmol. Vis. Sci</journal-id>
<journal-id journal-id-type="hwp">iovs</journal-id>
<journal-id journal-id-type="pmc">iovs</journal-id>
<journal-id journal-id-type="publisher-id">IOVS</journal-id>
<journal-title-group><journal-title>Investigative Ophthalmology & Visual Science</journal-title>
</journal-title-group>
<issn pub-type="ppub">0146-0404</issn>
<issn pub-type="epub">1552-5783</issn>
<publisher><publisher-name>The Association for Research in Vision and Ophthalmology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24781940</article-id>
<article-id pub-id-type="pmc">4039380</article-id>
<article-id pub-id-type="doi">10.1167/iovs.13-13779</article-id>
<article-id pub-id-type="sici">iovs-55-04-90</article-id>
<article-id pub-id-type="other">IOVS-13-13779</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
<subj-group><subject>Cornea</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Role of Angiopoietin-2 in Corneal Lymphangiogenesis</article-title>
<alt-title alt-title-type="runhead">Ang-2 in Lymphangiogenesis</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Yuen</surname>
<given-names>Don</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Grimaldo</surname>
<given-names>Sammy</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sessa</surname>
<given-names>Roberto</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ecoiffier</surname>
<given-names>Tatiana</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Truong</surname>
<given-names>Tan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Huang</surname>
<given-names>Eric</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bernas</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Daley</surname>
<given-names>Sarah</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Witte</surname>
<given-names>Marlys</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Lu</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, Berkeley, California, United States</aff>
<aff id="aff2"><label>2</label>
Graduate Group in Vision Science, University of California, Berkeley, Berkeley, California, United States</aff>
<aff id="aff3"><label>3</label>
Department of Surgery, School of Medicine, University of Arizona, Tucson, Arizona, United States</aff>
<author-notes><corresp id="cor1">Correspondence: Lu Chen, 689 Minor Hall, University of California, Berkeley, CA 94720, USA; <email>chenlu@berkeley.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="epub"><day>29</day>
<month>5</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub"><month>5</month>
<year>2014</year>
</pub-date>
<volume>55</volume>
<issue>5</issue>
<fpage>3320</fpage>
<lpage>3327</lpage>
<history><date date-type="received"><day>16</day>
<month>12</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>21</day>
<month>4</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.</copyright-statement>
<copyright-year>2014</copyright-year>
</permissions>
<abstract><sec id="st1"><title>Purpose.</title>
<p>Lymphatic research has progressed rapidly in recent years. Lymphatic dysfunction has been found in myriad disorders from cancer metastasis to transplant rejection; however, effective treatment for lymphatic disorders is still limited. This study investigates the role of angiopoietin-2 (Ang-2) in corneal inflammatory lymphangiogenesis (LG) in vivo and in lymphatic endothelial cell (LEC) functions in vitro.</p>
</sec>
<sec id="st2"><title>Methods.</title>
<p>Standard suture placement model was used to study Ang-2 expression in inflamed cornea, and corneal LG and hemangiogenesis (HG) responses in Ang-2 knockout mice. Moreover, human LEC culture system was used to examine the effect of Ang-2 gene knockdown on LEC functions using small interfering RNAs (siRNAs). The effect of siRNA treatment on corneal LG was also assessed in vivo.</p>
</sec>
<sec id="st3"><title>Results.</title>
<p>Angiopoietin-2 was expressed on lymphatic vessels and macrophages in inflamed cornea. While corneal LG response was abolished in Ang-2 knockout mice, the HG response was also significantly suppressed with disorganized patterning. Moreover, anti-Ang-2 treatment inhibited LEC proliferation and capillary tube formation in vitro and corneal LG in vivo.</p>
</sec>
<sec id="st4"><title>Conclusions.</title>
<p>Angiopoietin-2 is critically involved in lymphatic processes in vivo and in vitro. Further investigation of the Ang-2 pathway may provide novel insights and therapeutic strategies for lymphatic-related disorders, which occur both inside and outside the eye.</p>
</sec>
</abstract>
<abstract abstract-type="precis"><p>This study reveals Ang-2 gene deficiency leads to marked suppression of lymphangiogenesis in vivo and lymphatic endothelial cell functions in intro. Future investigation on Ang-2 pathway may provide novel therapeutic strategies for lymphatic-related diseases.</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>corneal lymphangiogenesis</kwd>
<kwd>Ang-2</kwd>
<kwd>knockout mice</kwd>
<kwd>small interfering RNA</kwd>
<kwd>lymphatic endothelial cells</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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