Universität zu Köln

Bock, Felix and Cursiefen, Claus (2017). Anti(lymph)angiogenic Strategies to Improve Corneal Graft Survival. Klinische Monatsblat. Augenheilkunde, 234 (5). S. 674 - 679. STUTTGART: GEORG THIEME VERLAG KG. ISSN 1439-3999

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Abstract

Corneal transplantation (keratoplasty) is the most frequently performed form of transplantation worldwide. A rejection reaction against the transplant is the main complication occurring after transplantation in an already vascularized, so-called high-risk recipient eye. Our group has shown that clinically invisible lymphatic vessels play a crucial role in the induction of a rejection reaction against the corneal graft, and that anti-(lymph) angiogenic therapies in the mouse model of keratoplasty can significantly improve transplant survival. The underlying mechanisms, which improve transplant survival through anti-lymphangiogenic therapies have not been well understood. We assume that the blockade of lymph vessel sprouting leads to a tolerance (and not to a simple ignorance) of the transplant, in which the antigen-presenting cells are held longer in the cornea and, thus, an immunomodulation of these cells occurs. Therefore, an important goal of our project is to find out whether and when transplant tolerance comes from a corneal anti-lymphangiogenic therapy. We assume that the antigen-presenting cells will have a different maturity level and that more tolerogenic effector cells (regulatory T cells, Tregs) develop in the absence of lymphatic vessels. Current anti(lymph) angiogenic therapies have the disadvantage that they are primarily effective on actively growing vessels. Most patients who receive high-risk keratoplasty often present in the clinic with already established, mature corneal blood and lymphatic vessels. At present, there are no lymph vessel regressing strategies, and the mechanisms regulating the maturation of the lymphatics are largely unknown. Therefore, our second goal is to develop new strategies for the regression of existing, pathological lymphatic vessels in the cornea. We are testing both destructive strategies, such as photodynamic therapy and diathermy as well as strategies for the molecular destabilization of the lymph vessel endothelium. Thus, our project identifies the precise mechanisms by which anti-lymphangiogenic therapies improve transplant survival, and we are developing new strategies to push back mature lymphatics in the high-risk setting.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-232079
DOI:	10.1055/s-0043-108248
Journal or Publication Title:	Klinische Monatsblat. Augenheilkunde
Volume:	234
Number:	5
Page Range:	S. 674 - 679
Date:	2017
Publisher:	GEORG THIEME VERLAG KG
Place of Publication:	STUTTGART
ISSN:	1439-3999
Language:	German
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FINE-NEEDLE DIATHERMY; SOLUBLE CD83; EYE DROPS; TOPICAL BEVACIZUMAB; ALLOGRAFT-REJECTION; SAFETY PROFILE; BLOOD-VESSELS; NEOVASCULARIZATION; LYMPHANGIOGENESIS; TRANSPLANTATION Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23207