{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:09:35Z","timestamp":1793189375484,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,11,16]],"date-time":"2011-11-16T00:00:00Z","timestamp":1321401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI050775"],"award-info":[{"award-number":["AI050775"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    LYVE\u20101\n                    <jats:sup>+<\/jats:sup>\n                    corneal lymphatics contribute to drainage and immunity. LYVE\u20101 is widely accepted as the most reliable lymphatic marker because of its continuous expression in lymphatic endothelium. LYVE\u20101 expression in corneal lymphatics has not been examined. In this study, we report intact CD31\n                    <jats:sup>+<\/jats:sup>\n                    corneal lymphatic capillary endothelial cells that do not express LYVE\u20101. The number of LYVE\u20101\n                    <jats:sup>\u2010<\/jats:sup>\n                    gaps initially increased until 8 wk of age but was significantly reduced in aged mice. C57BL\/6 mice showed a notably higher number of the LYVE\u20101\n                    <jats:sup>\u2010<\/jats:sup>\n                    \/CD31\n                    <jats:sup>+<\/jats:sup>\n                    lymphatic regions than BALB\/c mice, which suggests a genetic predisposition for this histological feature. The LYVE\u20101\n                    <jats:sup>\u2010<\/jats:sup>\n                    lymphatic gaps expressed podoplanin and VE\u2010cadherin but not \u03b1SMA or FOXC2. Interestingly, the number of LYVE\u20101\n                    <jats:sup>\u2010<\/jats:sup>\n                    gaps in FGF\u20102, but not VEGF\u2010A, implanted corneas was significantly lower than in untreated corneas. Over 70% of the CD45\n                    <jats:sup>+<\/jats:sup>\n                    leukocytes were found in the proximity of the LYVE\u20101\n                    <jats:sup>\u2010<\/jats:sup>\n                    gaps. Using a novel\n                    <jats:italic>in vivo<\/jats:italic>\n                    imaging technique for visualization of leukocyte migration into and out of corneal stroma, we showed reentry of extravasated leukocytes from angiogenic vessels into newly grown corneal lymphatics. This process was inhibited by VE\u2010cadherin blockade. To date, existence of lymphatic valves in cornea is unknown. Electron microscopy showed overlapping lymphatic endothelial ends, reminiscent of microvalves in corneal lymphatics. This work introduces a novel corneal endothelial lymphatic phenotype that lacks LYVE\u20101. LYVE\u20101\n                    <jats:sup>\u2010<\/jats:sup>\n                    lymphatic endothelium could serve as microvalves, supporting unidirectional flow, as well as immunological hot spots that facilitate reentry of stromal macropahges.\u2014Nakao, S., Zandi, S., Faez, S., Kohno, R., Hafezi\u2010Moghadam, A. Discontinuous LYVE\u20101 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 808\u2013817 (2012). www.fasebj.org\n                  <\/jats:p>","DOI":"10.1096\/fj.11-183897","type":"journal-article","created":{"date-parts":[[2011,11,17]],"date-time":"2011-11-17T07:39:19Z","timestamp":1321515559000},"page":"808-817","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Discontinuous LYVE\u20101 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots"],"prefix":"10.1096","volume":"26","author":[{"given":"Shintaro","family":"Nakao","sequence":"first","affiliation":[{"name":"Center for Excellence in Functional and Molecular Imaging Brigham and Women's Hospital"},{"name":"Department of Radiology, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"},{"name":"Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Ophthalmology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souska","family":"Zandi","sequence":"additional","affiliation":[{"name":"Center for Excellence in Functional and Molecular Imaging Brigham and Women's Hospital"},{"name":"Department of Radiology, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"},{"name":"Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Faez","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri\u2010ichiro","family":"Kohno","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Hafezi\u2010Moghadam","sequence":"additional","affiliation":[{"name":"Center for Excellence in Functional and Molecular Imaging Brigham and Women's Hospital"},{"name":"Department of Radiology, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"},{"name":"Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,16]]},"reference":[{"key":"e_1_2_20_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathmechdis.3.121806.151515"},{"key":"e_1_2_20_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-134056"},{"key":"e_1_2_20_4_1","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0140-6736(63)91543-5","article-title":"The lymphatic system in the resorption of homologous serum from the cornea","volume":"1","author":"Szeghy G.","year":"1963","journal-title":"Lancet"},{"key":"e_1_2_20_5_1","first-page":"146","article-title":"Lymphatic drainage of 131\u2010I\u2010albumin from the vascularized cornea","volume":"9","author":"Collin H. 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