scholarly journals Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival

2020 ◽  
Vol 9 (5) ◽  
pp. 1280
Author(s):  
Alfrun Schönberg ◽  
Matthias Hamdorf ◽  
Felix Bock
Keyword(s):  
Dendritic Cells ◽  
Risk Factor ◽  
Common Sense ◽  
Gold Standard ◽  
Corneal Transplantation ◽  
Lymphatic Vessels ◽  
Therapeutic Strategies ◽  
Allograft Survival ◽  
Corneal Allograft ◽  
Vessel Regression

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.

Ripasudil zur antiangiogenen Therapie bei Keratoplastik

2021 ◽  
pp. 1-2
Author(s):  
Björn Bachmann
Keyword(s):  
Graft Survival ◽  
Immune Cell ◽  
Kinase Inhibitor ◽  
Healing Process ◽  
Corneal Transplantation ◽  
Inflammatory Factors ◽  
Wound Healing Process ◽  
Mrna Levels ◽  
Allograft Survival ◽  
Corneal Allograft

Corneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic corneal transplantation. Corneal graft survival, opacity, neovascularization, re-epithelization, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in the grafted cornea and draining lymph nodes (dLNs) were evaluated with slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. Graft survival was significantly prolonged with lower graft opacity and neovascularization scores in 0.4% and 2.0% ripasudil-treated groups, and mRNA levels of angiogenic and pro-inflammatory factors in ripasudil-treated grafted corneas were reduced. Moreover, 0.4% and 2.0% ripasudil reduced CD45<sup>+</sup>-infiltrated leukocyte frequency, <i>Cd11b</i> and <i>Cd11c</i> mRNA levels, and the frequencies of mature dendritic cells, IFNγ-, and IL-17- producing CD4<sup>+</sup>T cells in the dLNs of recipients. Re-epithelization rate of the grafted cornea was significantly higher in the 0.4% and 2.0% ripasudil groups than in the control. Topically applied ripasudil prolonged graft survival by downregulating neovascularization and inflammation factors, while promoting corneal re-epithelization, suggesting that ripasudil may be useful for suppressing immunological rejection in corneal transplantation.

scholarly journals Donor Bone Marrow–derived Dendritic Cells Prolong Corneal Allograft Survival and Promote an Intragraft Immunoregulatory Milieu

2013 ◽  
Vol 21 (11) ◽  
pp. 2102-2112 ◽  
Author(s):  
Lisa O'Flynn ◽  
Oliver Treacy ◽  
Aideen E Ryan ◽  
Maurice Morcos ◽  
Marese Cregg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Allograft Survival ◽  
Corneal Allograft ◽  
Donor Bone Marrow

scholarly journals Novel immunotherapeutic effects of topically administered ripasudil (K-115) on corneal allograft survival

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takenori Inomata ◽  
Keiichi Fujimoto ◽  
Yuichi Okumura ◽  
Jun Zhu ◽  
Kenta Fujio ◽  
...  
Keyword(s):  
Graft Survival ◽  
Immune Cell ◽  
Kinase Inhibitor ◽  
Healing Process ◽  
Corneal Transplantation ◽  
Inflammatory Factors ◽  
Wound Healing Process ◽  
Mrna Levels ◽  
Allograft Survival ◽  
Corneal Allograft

AbstractCorneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic corneal transplantation. Corneal graft survival, opacity, neovascularization, re-epithelization, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in the grafted cornea and draining lymph nodes (dLNs) were evaluated with slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. Graft survival was significantly prolonged with lower graft opacity and neovascularization scores in 0.4% and 2.0% ripasudil-treated groups, and mRNA levels of angiogenic and pro-inflammatory factors in ripasudil-treated grafted corneas were reduced. Moreover, 0.4% and 2.0% ripasudil reduced CD45+-infiltrated leukocyte frequency, Cd11b and Cd11c mRNA levels, and the frequencies of mature dendritic cells, IFNγ-, and IL-17- producing CD4+T cells in the dLNs of recipients. Re-epithelization rate of the grafted cornea was significantly higher in the 0.4% and 2.0% ripasudil groups than in the control. Topically applied ripasudil prolonged graft survival by downregulating neovascularization and inflammation factors, while promoting corneal re-epithelization, suggesting that ripasudil may be useful for suppressing immunological rejection in corneal transplantation.

Donor bone marrow derived dendritic cells promote corneal allograft survival in the rat

2012 ◽  
Vol 90 ◽  
pp. 0-0
Author(s):  
L O'FLYNN ◽  
O TREACY ◽  
A RYAN ◽  
M MORCOS ◽  
M NOSOV ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Allograft Survival ◽  
Corneal Allograft ◽  
Donor Bone Marrow

scholarly journals The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shang Li ◽  
Jing Yu ◽  
Chungang Guo ◽  
Ying Jie ◽  
Zhiqiang Pan
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Aqueous Humor ◽  
Allograft Rejection ◽  
Corneal Transplantation ◽  
Allograft Survival ◽  
Survival Group ◽  
Corneal Allograft ◽  
Group 3 ◽  
Corneal Allograft Rejection

Purpose. CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods. A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. Results. The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. Conclusion. LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

scholarly journals Subconjunctival administration of low-dose murine allogeneic mesenchymal stromal cells promotes corneal allograft survival in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Oliver Treacy ◽  
Kevin Lynch ◽  
Nick Murphy ◽  
Xizhe Chen ◽  
Ellen Donohoe ◽  
...  
Keyword(s):  
Graft Survival ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Low Dose ◽  
Corneal Transplantation ◽  
Corneal Transplant ◽  
Subconjunctival Injection ◽  
Allograft Survival ◽  
Corneal Allograft ◽  
Allogeneic Mscs

Abstract Background Systemic administration of mesenchymal stromal cells (MSCs) has been efficacious in many inflammatory disease settings; however, little data are available on the potential immunomodulatory effects following local MSC administration in the context of corneal transplantation. The purpose of this study was to assess the potential of subconjunctival injection of MSCs to promote corneal allograft survival. Methods MSCs were isolated from female C57BL/6 (H-2k) or Balb/c (H-2d) mice and extensively characterized. An allogeneic mouse corneal transplant model was used with Balb/c mice as recipients of C57BL/6 grafts. A dose-finding study starting with 5 × 105 MSCs injected subconjunctivally at day − 7 was tested first followed by a more clinically translatable low-dose single or dual injection strategy on day − 1 and day + 1 before/after transplantation. Graft transparency served as the primary indicator of transplant rejection while neovascularization was also recorded. Lymphocytes (from draining lymph nodes) and splenocytes were isolated from treatment groups on day 2 post-transplantation and characterized by flow cytometry and qRT-PCR. Results Both high- and low-dose injection of allogeneic MSCs on day − 7 led to 100% graft survival over the observation period. Moreover, low-dose dual subconjunctival injection of 5 × 104 allogeneic MSCs on day − 1 or day + 1 led to 100% allograft survival in transplant recipients (n = 7). We also demonstrate that single administration of allogeneic MSCs on either day − 1 or day + 1 promotes rejection-free graft survival in 100% (n = 8) and 86% (n = 7) of transplanted mice, respectively. Early time point ex vivo analysis suggests modulation of innate immune responses towards anti-inflammatory, pro-repair responses by local MSC administration. Conclusion This work demonstrates that low-dose subconjunctival injection of allogeneic MSCs successfully promotes corneal allograft survival and may contribute to refining future MSC immunotherapies for prevention of corneal allograft rejection.

scholarly journals Celastrol-based nanomedicine promotes corneal allograft survival

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhanrong Li ◽  
Ruixing Liu ◽  
Zhihua Guo ◽  
Dandan Chu ◽  
Lei Zhu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Corneal Transplantation ◽  
Anterior Segment ◽  
Eye Drops ◽  
Allograft Survival ◽  
Corneal Permeability ◽  
Corneal Allograft ◽  
M1 Macrophage

AbstractEffectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases. Graphical Abstract

Influence of local and systemic CTLA4Ig gene transfer on corneal allograft survival

2006 ◽  
Vol 8 (4) ◽  
pp. 459-467 ◽  
Author(s):  
Nianqiao Gong ◽  
Uwe Pleyer ◽  
Jun Yang ◽  
Katrin Vogt ◽  
Marcelo Hill ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Allograft Survival ◽  
Corneal Allograft
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