Universität zu Köln

Reuer, Tristan, Schneider, Ann-Charlott, Cakir, Bertan, Buehler, Anima D., Walz, Johanna M., Lapp, Thabo ORCID: 0000-0001-7097-7587, Lange, Clemens, Agostini, Hansjuergen, Schlunck, Guenther, Cursiefen, Claus, Reinhard, Thomas, Bock, Felix and Stahl, Andreas (2018). Semaphorin 3F Modulates Corneal Lymphangiogenesis and Promotes Corneal Graft Survival. Invest. Ophthalmol. Vis. Sci., 59 (12). S. 5277 - 5285. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. Corneal vascularization significantly increases the risk for graft rejection after keratoplasty. Semaphorin 3F (Sema3F) is a known modulator of physiologic avascularity in the outer retina. The aim of this study was to investigate whether Sema3F is involved in maintaining corneal avascularity and can reduce the risk for corneal graft rejection. METHODS. Corneal Sema3F expression was investigated using immunohistochemistry and qPCR in human and murine tissue. Pathologic invasion of blood and lymph vessels into corneal tissue was analyzed in the murine corneal suture and high-risk keratoplasty model. The anti-lymphangiogenic effects of Sema3F were further investigated using an in vitro spheroidal sprouting model with supernatant from isolated primary human corneal epithelial cells (hCECs). RESULTS. Sema3F is constitutively expressed in human and murine corneal epithelium. In the corneal suture model, lymphangiogenesis was significantly suppressed by topical Sema3F treatment (P = 0.0003). In the murine high-risk keratoplasty model, pretreatment by topical Sema3F in the inflammation phase significantly promoted subsequent graft survival (P = 0.0006). In this model, both lymph-and blood angiogenesis were reduced (P < 0.05). In vitro, hCEC supernatant had a direct anti-lymphangiogenic effect on human lymphatic endothelial cells (P < 0.01). This effect was completely abolished by addition of anti-Sema3F antibodies. CONCLUSIONS. Sema3F is a novel mediator of corneal avascularity with potent antilymphangiogenic properties. Topical treatment with Sema3F eye drops may help to limit corneal vascularization and improve outcomes in high-risk keratoplasty patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reuer, Tristan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Ann-Charlott UNSPECIFIED UNSPECIFIED UNSPECIFIED Cakir, Bertan UNSPECIFIED UNSPECIFIED UNSPECIFIED Buehler, Anima D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Walz, Johanna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lapp, Thabo UNSPECIFIED orcid.org/0000-0001-7097-7587 UNSPECIFIED Lange, Clemens UNSPECIFIED UNSPECIFIED UNSPECIFIED Agostini, Hansjuergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlunck, Guenther UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhard, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Stahl, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-170713
DOI:	10.1167/iovs.18-24287
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	59
Number:	12
Page Range:	S. 5277 - 5285
Date:	2018
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSPLANTATION; EXPRESSION; ANGIOGENESIS; AVASCULARITY; REJECTION; CELLS; NEOVASCULARIZATION; INHIBITOR; RECEPTORS; RETINA Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17071