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New Insights into Corneal Regeneration and Transplantation
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New Insights into Corneal Regeneration and Transplantation

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4437

Special Issue Editors

Dr. Zala Lužnik Marzidovšek

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Guest Editor
Eye Hospital, Ljubljana University Medical Centre, Ljubljana, Slovenia
Interests: cornea; corneal surface disease; corneal transplantation; eye banking; corneal stem cells; corneal immunology
Dr. Rohan Bir Singh

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Guest Editor
1. Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
2. Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands
3. Discipline of Ophthalmology and Visual Sciences, Faculty of Health and Medical Sciences, Adelaide Medical School, University of Adelaide, Adelaide, Australia
Interests: cornea; dry eye disease; corneal transplantation; corneal regeneration; epidemiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to announce the launch of our upcoming Special Issue ‘New Insights into Corneal Regeneration and Transplantation’, which will feature in the Journal of Clinical Medicine. The cornea, as a vital ocular structure, plays an irreplaceable role in maintaining visual acuity and overall eye health. However, its susceptibility to injury, disease, and degeneration necessitates an in-depth understanding of regenerative therapies and transplantation techniques.

This Special Issue invites contributions from scientists, clinicians and leading experts in the fields of ophthalmology, eye banking, and transplantation, who have conducted pioneering and well-founded research on the intricacies of corneal regeneration and transplantation. Through a multidisciplinary lens, this Special Issue will ensure to provide insights into a wide array of the latest innovative strategies, such as stem cell therapies, tissue-engineered constructs, and immunomodulatory interventions, that have revolutionized the practical applications of corneal treatments. Moreover, we also aim to include studies addressing the challenges of immune rejection, graft survival, and functional restoration, thereby heralding a new era of precision medicine in ocular care.

We sincerely hope that this Special Issue will not only strengthen the knowledge of current advancements in ocular care but also pave the way for novel explorations, fostering improved clinical outcomes and an enhanced quality of life for countless individuals.

Dr. Zala Lužnik Marzidovšek
Dr. Rohan Bir Singh
Guest Editors

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

  • cornea
  • corneal surface disease
  • corneal transplantation
  • eye banking
  • corneal stem cells
  • corneal immunology

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Published Papers (4 papers)

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12 pages, 2655 KiB  
Article
Assessment of Corneal Graft Outcomes in a Murine Model of Endothelial Keratoplasty
by Akitomo Narimatsu, Rohan Bir Singh, Pier Luigi Surico, Seokjoo Lee, Katayoon Forouzanfar, Francesca Kahale, Aytan Musayeva, Thomas H. Dohlman, Tomas Blanco and Reza Dana
J. Clin. Med. 2024, 13(17), 5010; https://doi.org/10.3390/jcm13175010 - 24 Aug 2024
Viewed by 783
Abstract
Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) [...] Read more.
Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) as donors and BALB/c mice as recipients. Slit-lamp examination and optical coherence tomography were performed for clinical evaluations for 16 weeks post-procedure. Criteria for the assessment of corneal opacity were established and the animals were graded weekly. Additionally, we assessed corneal endothelial cell density by harvesting the corneas and staining with zonula occludens-1 (ZO-1). Lastly, lymph nodes were collected, and CD4+ T cells were MACS-sorted and co-cultured with syngeneic or allogeneic antigen-presenting cells (APCs) to assess the IFN-γ expression levels by alloreactive Th1 cells (ELISPOT) in response to the direct (donor) or indirect (host) pathways of sensitization. Results: We observed graft failure in four animals, including irreversible corneal opacity, graft detachment, and anterior synechiae in the first four weeks. The remaining animals were graded between 0 and 5 as per the established criteria. The total and graft corneal thickness and endothelial cell density progressively worsened with a higher grade of corneal opacity. The direct allosensitization of Th1 cells was significantly higher in mice with a higher grade of corneal opacity. At 16 weeks follow-up, the grafts remained stable with low opacity scores in syngeneic EK recipients; however, the opacity scores were higher and variable in allogeneic EK recipients. Conclusions: These findings establish a standardized protocol to assess the graft outcomes in a murine model of EK. Furthermore, we delineate the underlying immunological pathway that contributes to the immune-mediated rejection of grafts in this model. Full article
(This article belongs to the Special Issue New Insights into Corneal Regeneration and Transplantation)
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11 pages, 1062 KiB  
Article
Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation
by Tina Dietrich-Ntoukas, Felix Bock, Jasmine Onderka, Deniz Hos, Bjoern O. Bachmann, Grit Zahn and Claus Cursiefen
J. Clin. Med. 2024, 13(15), 4418; https://doi.org/10.3390/jcm13154418 - 28 Jul 2024
Viewed by 982
Abstract
Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from [...] Read more.
Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from C57BL/6 mice to BalbC mice was performed as “high-risk” keratoplasty in a prevascularized corneal host bed (suture-induced inflammatory corneal neovascularization). The treatment group received integrin α5β1-blocking small molecules (JSM6427) at the time of transplantation and for two weeks afterwards. Control mice received a vehicle solution. Grafts were evaluated weekly for graft rejection using an opacity score. At the end of the follow-up, immunohistochemical staining of corneal wholemounts for lymphatic vessels as well as CD11b+ immune cells was performed. Results: Temporary postoperative inhibition of lymphangiogenesis by JSM6427 improved the corneal graft survival significantly. At the end of the follow-up, no significant reduction in CD11b+ immunoreactive cells within the graft compared to controls was found. Conclusions: The significant improvement of corneal graft survival by the selective, temporary postoperative inhibition of lymphangiogenesis after keratoplasty using integrin antagonists shows the impact of lymphatic vessels in the early postoperative phase. Retarding lymphatic vessel ingrowth into the graft might be sufficient for the shift to immunological tolerance in the postoperative period, even after high-risk keratoplasty. Full article
(This article belongs to the Special Issue New Insights into Corneal Regeneration and Transplantation)
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12 pages, 400 KiB  
Article
Risk Factors for Corneal Endothelial Decompensation after Penetrating Keratoplasty: A Population-Based Cohort Study
by Hung-Chi Chen, Chia-Yi Lee, Yu-Ling Chang, Jing-Yang Huang, Shun-Fa Yang and Chao-Kai Chang
J. Clin. Med. 2024, 13(3), 718; https://doi.org/10.3390/jcm13030718 - 26 Jan 2024
Viewed by 1430
Abstract
(1) Background: Endothelial decompensation is a common complication after penetrating keratopathy (PK), while the risk factors for endothelial decompensation after PK have not been fully elucidated. Consequently, we aim to investigate the possible risk factors for endothelial decompensation after PK. (2) Methods: This [...] Read more.
(1) Background: Endothelial decompensation is a common complication after penetrating keratopathy (PK), while the risk factors for endothelial decompensation after PK have not been fully elucidated. Consequently, we aim to investigate the possible risk factors for endothelial decompensation after PK. (2) Methods: This retrospective study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. The main outcome was the development of endothelial decompensation after PK surgery. The effects of potential risk factors were compared between the patients with endothelial decompensation and the patients without endothelial decompensation via Cox proportional hazard regression, which produced the adjusted hazard ratio (aHR) and a 95% confidence interval (CI). (3) Results: Overall, 54 patients developed endothelial decompensation after PK surgery, with a ratio of 16.12 percent. The pre-existing type 2 diabetes mellitus (T2DM) (aHR: 1.924, 95% CI: 1.257–2.533, p = 0.0095) and history of cataract surgery (aHR: 1.687, 95% CI: 1.328–2.440, p = 0.0026) were correlated with the development of endothelial decompensation. In the subgroup analysis, the correlation between a history of cataract surgery and post-PK endothelial decompensation was more prominent in patients older than 60 years compared to their younger counterparts (p = 0.0038). (4) Conclusions: Pre-existing T2DM and a history of cataract surgery are associated with a higher incidence of post-PK endothelial decompensation. Full article
(This article belongs to the Special Issue New Insights into Corneal Regeneration and Transplantation)
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Other

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14 pages, 2910 KiB  
Systematic Review
A Functional and Immunologic Point of View on Corneal Endothelial Transplantation: A Systematic Review and Meta-Analysis
by Sara Spelta, Alessandra Micera, Daniele Gaudenzi, Matteo Niutta, Pier Luigi Surico, Antonio De Vincentis, Marco Coassin and Antonio Di Zazzo
J. Clin. Med. 2024, 13(12), 3431; https://doi.org/10.3390/jcm13123431 - 12 Jun 2024
Viewed by 753
Abstract
Background: To systematically review and meta-analyze the immunologic aspects and outcomes of various endothelial keratoplasty (EK) techniques, specifically comparing Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK), Ultra-Thin Descemet’s Stripping Automated Endothelial Keratoplasty (UT-DSAEK), and Descemet’s Membrane Endothelial Keratoplasty (DMEK). Methods: Systematic review and meta-analysis. [...] Read more.
Background: To systematically review and meta-analyze the immunologic aspects and outcomes of various endothelial keratoplasty (EK) techniques, specifically comparing Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK), Ultra-Thin Descemet’s Stripping Automated Endothelial Keratoplasty (UT-DSAEK), and Descemet’s Membrane Endothelial Keratoplasty (DMEK). Methods: Systematic review and meta-analysis. Main outcomes were the proportion of patients achieving a best spectacle-corrected visual acuity (BSCVA) of 20/20 at 6 months after keratoplasty, rejection rate one year after surgery, BSCVA at last follow up, and postoperative immunomodulating regimen. Results: A higher proportion of DMEK patients achieved a BSCVA of 20/20 after 6 months. UT-DSAEK and DMEK showed similar rejection rates with a lower risk of re-bubbling for UT-DSAEK (4% vs. 20%). Conclusions: DMEK showed faster visual recovery than UT-DSAEK but a similar rejection rate and long-term visual acuity. One-year postoperative slow tapering steroid regimen has a positive but not (yet) significant effect on rejection risk and visual outcomes. Full article
(This article belongs to the Special Issue New Insights into Corneal Regeneration and Transplantation)
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