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Corneal Transplant Immunology
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Corneal Transplant Immunology

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (29 February 2020)

Special Issue Editor

Dr. Felix Bock

E-Mail Website
Guest Editor
Laboratory Leader Cornea Lab, Experimental Ophthalmology LFI Gebäude 13, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany
Interests: transplant tolerance; immune modulation; dendritic cells; lymphangiogenesis

Special Issue Information

Dear Colleagues,

On behalf of the Journal of Clinical Medicine Editorial Team, I am delighted to present a Special Issue on the topic of “Corneal Transplant Immunology”.

Corneal inflammation and vascularisation is the main risk factor for corneal graft rejection. Hereby there is a close interaction between different cell types like dendritic cells, macrophages or T cell with vascular endothelials cell, epithelials cells, neurons and endothelial cells. On the other hand, new therapies have been developed over the last decade to improve corneal graft survival using anti-inflammatory or anti-angiogenic approaches.

This special issue will focus on the interaction of the immune cells with corneal structures and how new therapies can modulate these interactions.

The accepted papers will describe new insights in these areas. This Special Issue accepts high-quality articles containing original research results and case reports, as well as review articles of exceptional merit.

Dr. Felix Bock
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • corneal transplantation
  • immune cell interaction
  • immune modulation
  • inflammation

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

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Research

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13 pages, 1881 KiB  
Article
Topical VEGF-C/D Inhibition Prevents Lymphatic Vessel Ingrowth into Cornea but Does Not Improve Corneal Graft Survival
by Ann-Charlott Salabarria, Manuel Koch, Alfrun Schönberg, Elisabeth Zinser, Deniz Hos, Matthias Hamdorf, Thomas Imhof, Gabriele Braun, Claus Cursiefen and Felix Bock
J. Clin. Med. 2020, 9(5), 1270; https://doi.org/10.3390/jcm9051270 - 28 Apr 2020
Cited by 11 | Viewed by 3209
Abstract
Vascular endothelial growth factor-C/D (VEGF-C/D) regulates lymphangiogenesis. Ingrowth of lymphatic vessels is negatively associated with corneal transplantation success. In this study, we therefore analyzed the effect local blockade of VEGF-C/D has on inflamed corneas. We used the murine model of suture-induced neovascularization and [...] Read more.
Vascular endothelial growth factor-C/D (VEGF-C/D) regulates lymphangiogenesis. Ingrowth of lymphatic vessels is negatively associated with corneal transplantation success. In this study, we therefore analyzed the effect local blockade of VEGF-C/D has on inflamed corneas. We used the murine model of suture-induced neovascularization and subsequent high-risk corneal transplantation. Mice were treated with a VEGF-C/D trap prior to transplantation. Topical inhibition of VEGF-C/D significantly reduced lymphatic vessel ingrowth, but increased Macrophage numbers in the cornea. Furthermore, corneal transplantation success was not improved by the topical application of the compound. This study demonstrates that local VEGF-C/D inhibition is insufficient to increases corneal transplantation success, likely due to interaction with immune cells. Full article
(This article belongs to the Special Issue Corneal Transplant Immunology)
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14 pages, 2338 KiB  
Article
Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze
by Nobuyo Yawata, Sunita Awate, Yu-Chi Liu, Shi Yuan, Kaing Woon, Jay Siak, Yoh-Ichi Kawano, Koh-Hei Sonoda, Jodhbir S. Mehta and Makoto Yawata
J. Clin. Med. 2020, 9(1), 63; https://doi.org/10.3390/jcm9010063 - 26 Dec 2019
Cited by 4 | Viewed by 3057
Abstract
Endothelial keratoplasty (EK) is less invasive with faster recovery as compared to conventional penetrating keratoplasty, however, it relies on the clarity of the host corneal stroma. Corneal transplantation involves the induction of immune tolerance for allogeneic tissues as well as the corneal wound [...] Read more.
Endothelial keratoplasty (EK) is less invasive with faster recovery as compared to conventional penetrating keratoplasty, however, it relies on the clarity of the host corneal stroma. Corneal transplantation involves the induction of immune tolerance for allogeneic tissues as well as the corneal wound healing process, in which coordinated interactions between cytokines and growth factors are critical. In this study, we profiled the expression of 51 soluble factors in the tear fluid over the course of EK and have provided evidence of dynamic changes in cytokine expression in the ipsilateral and contralateral eyes. Cluster analyses classified the cytokine expression kinetics into five groups. Group 1 proteins included TGF-b1, IL-1b, and innate proinflammatory cytokines, which bilaterally increased after surgery, despite the use of topical corticosteroid in the transplanted eyes. Local corticosteroids suppressed cytokines involved in adaptive immunity in the transplanted eyes but not in the contralateral eyes. We found tear protein expression at baseline and one week post-surgery to be a potential predictive biomarker of delayed recovery after EK in terms of the corneal haze and visual acuity. Furthermore, Group 1 tear proteins were most associated with persistent corneal haze pre-surgery as well as visual acuity at one month-post transplant. Full article
(This article belongs to the Special Issue Corneal Transplant Immunology)
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13 pages, 2276 KiB  
Article
Bevacizumab Induces Upregulation of Keratin 3 and VEGFA in Human Limbal Epithelial Cells in Vitro
by Maria Notara, Anna Lentzsch, Thomas Clahsen, Sara Behboudifard, Gabriele Braun and Claus Cursiefen
J. Clin. Med. 2019, 8(11), 1925; https://doi.org/10.3390/jcm8111925 - 9 Nov 2019
Cited by 7 | Viewed by 2747
Abstract
Topical application of vascular endothelial growth factor A (VEGFA) inhibitors including Bevacizumab is used for antiangiogenic therapy at the ocular surface. While clinical studies have suggested that this approach is well-tolerated, the effect of the drug on limbal epithelial stem cells has not [...] Read more.
Topical application of vascular endothelial growth factor A (VEGFA) inhibitors including Bevacizumab is used for antiangiogenic therapy at the ocular surface. While clinical studies have suggested that this approach is well-tolerated, the effect of the drug on limbal epithelial stem cells has not been studied. In this study, the effect of Bevacizumab on phenotype and functionality of putative limbal epithelial stem cells (SC) was investigated. The effect of Bevacizumab on human limbal epithelial cells was assessed in terms of metabolic activity and scratch wound closure. The different treatment groups featured no difference in proliferation and colony forming efficiency (CFE) of limbal epithelial cells or their putative SC marker expression. A significant delay in scratch closure of all the Bevacizumab-treated groups was detected at 4 h. RNA and protein quantification indicated a dose-responsive increase of keratin 3. VEGFA RNA expression also increased while VEGFC and D as well as VEGFR1, 2 and 3 were unchanged. This study highlights previously unknown effects of Bevacizumab on cultured putative limbal epithelial SC: a dose-related increase of keratin 3, an increase in VEGFA as well as a delay in scratch wound closure. These in vitro data should be considered when using Bevacizumab in the context of limbal epithelial SC transplantation. Full article
(This article belongs to the Special Issue Corneal Transplant Immunology)
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Review

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21 pages, 1239 KiB  
Review
Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival
by Alfrun Schönberg, Matthias Hamdorf and Felix Bock
J. Clin. Med. 2020, 9(5), 1280; https://doi.org/10.3390/jcm9051280 - 28 Apr 2020
Cited by 14 | Viewed by 3512
Abstract
Even though the cornea is regarded as an immune-privileged tissue, transplantation always comes with the risk of rejection due to mismatches between donor and recipient. It is common sense that an alternative to corticosteroids as the current gold standard for treatment of corneal [...] Read more.
Even though the cornea is regarded as an immune-privileged tissue, transplantation always comes with the risk of rejection due to mismatches between donor and recipient. It is common sense that an alternative to corticosteroids as the current gold standard for treatment of corneal transplantation is needed. Since blood and lymphatic vessels have been identified as a severe risk factor for corneal allograft survival, much research has focused on vessel regression or inhibition of hem- and lymphangiogenesis in general. However, lymphatic vessels have been identified as required for the inflammation’s resolution. Therefore, targeting other players of corneal engraftment could reveal new therapeutic strategies. The establishment of a tolerogenic microenvironment at the graft site would leave the recipient with the ability to manage pathogenic conditions independent from transplantation. Dendritic cells (DCs) as the central player of the immune system represent a target that allows the induction of tolerogenic mechanisms by many different strategies. These strategies are reviewed in this article with regard to their success in corneal transplantation. Full article
(This article belongs to the Special Issue Corneal Transplant Immunology)
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21 pages, 866 KiB  
Review
Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology
by Antonio Di Zazzo, Sang-Mok Lee, Jaemyoung Sung, Matteo Niutta, Marco Coassin, Alireza Mashaghi and Takenori Inomata
J. Clin. Med. 2020, 9(2), 586; https://doi.org/10.3390/jcm9020586 - 21 Feb 2020
Cited by 30 | Viewed by 5159
Abstract
Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction [...] Read more.
Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction method would impact therapeutic decision-making in corneal transplantation. Valuable insights into the clinically observed heterogeneity of host responses to corneal grafts have emerged from multidisciplinary approaches, including genomics analyses, mechanical studies, immunobiology, and theoretical modeling. Here, we review the emerging concepts, tools, and new biomarkers that may allow for the prediction of graft survival. Full article
(This article belongs to the Special Issue Corneal Transplant Immunology)
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20 pages, 2828 KiB  
Review
Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation
by Thomas Clahsen, Christian Büttner, Niloofar Hatami, André Reis and Claus Cursiefen
J. Clin. Med. 2020, 9(2), 479; https://doi.org/10.3390/jcm9020479 - 9 Feb 2020
Cited by 12 | Viewed by 3912
Abstract
Under normal conditions, the cornea, being the transparent “windscreen” of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of [...] Read more.
Under normal conditions, the cornea, being the transparent “windscreen” of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem- and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem- and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea. Full article
(This article belongs to the Special Issue Corneal Transplant Immunology)
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