Alloimmunity and Tolerance in Corneal Transplantation

Amouzegar, Afsaneh; Chauhan, Sunil; Dana, Reza

doi:10.4049/jimmunol.1600251

Cited by 107 publications

(133 citation statements)

References 101 publications

(121 reference statements)

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…The avascular nature of the cornea, unique physiology of the anterior chamber recognized as Anterior Chamber Associated Immune Deviation (ACAID), low to absent expression of major histocompatibility antigens (MHC)-I and II in the cornea, quiescent corneal antigen-presenting cells (APCs), and presence of T cell apoptotic factors like Fas-ligand are some of the factors responsible for high survival rates of corneal allografts. 5,89 …”

Section: Immunology and Pathophysiology Of Corneal Graft Failurementioning

confidence: 99%

“…The efferent phase, mediated by delivery of immune effectors to the graft site by blood vessels, is responsible for ultimately attacking the graft through a T cell dependent effector mechanism- both CD8+ and CD4+ Tcells which release inflammatory cytokines like interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-10, subsequently resulting in graft rejection. 5,89 …”

Section: Immunology and Pathophysiology Of Corneal Graft Failurementioning

confidence: 99%

“…Regulatory immune cells actively dampen the immune response against foreign alloantigens and induce allotolerance of corneal transplants. 5 Regulatory T cells (Tregs) and maturation-resistant tolerogenic dendritic cells (tolDCs) have been used in experimental models to induce tolerance and thus eliminate the use of immunosuppressive agents. 61,63,104 It has been shown that in vitro expansion of Tregs can also significantly promote allograft survival.…”

Section: Novel Strategies For Immunomodulation In Corneal Transplamentioning

confidence: 99%

See 2 more Smart Citations

Management of high-risk corneal transplantation

Zazzo

Kheirkhah

Abud

et al. 2017

Survey of Ophthalmology

Self Cite

124

102

View full text Add to dashboard Cite

The cornea is the most commonly transplanted tissue in medicine. The main cause of corneal graft failure is allograft rejection. The incidence of graft rejection depends on the presence of high-risk characteristics, most notably corneal neovascularization. Although corneal graft has high success rates in the absence of these risk factors, high-risk keratoplasty is associated with low success rates due to a high incidence of immune-mediated graft rejection. To improve the survival of high-risk corneal transplantation, various preoperative, intraoperative, and postoperative measures can be considered. However, the key step in the management of these grafts is the long-term use of local and/or systemic immunosuppressive agents. Although a number of immunosuppressive agents have been employed for this purpose, the results vary significantly across different studies. This is partly due to the lack of an optimized method for their use as well as the lack of a precise stratification of the degree of risk in each individual patient. New targeted biologic treatments as well as tolerance-inducing methods show promising horizons in the management of high-risk corneal transplantation in near future.

show abstract

Section: Immunology and Pathophysiology Of Corneal Graft Failurementioning

confidence: 99%

Section: Immunology and Pathophysiology Of Corneal Graft Failurementioning

confidence: 99%

Section: Novel Strategies For Immunomodulation In Corneal Transplamentioning

confidence: 99%

See 1 more Smart Citation

Management of high-risk corneal transplantation

Zazzo

Kheirkhah

Abud

et al. 2017

Survey of Ophthalmology

Self Cite

124

102

View full text Add to dashboard Cite

show abstract

“…Corneal allografts normally enjoy very high survival rates due to tolerogenic mechanisms that account for ocular immune privilege 26) ; however, in settings of graft site inflammation (ʻhigh-riskʼ transplantation), the risk of a prompt rejection becomes a near absolute certainty 27)-29)…”

Section: Discussionmentioning

confidence: 99%

A New Immunotherapy Using Regulatory T-Cells for High-Risk Corneal Transplantation

Inomata

2017

Juntendo Medical Journal

View full text Add to dashboard Cite

Corneal transplantation is the most commonly performed tissue transplantation worldwide. Despite very high (above 90%) survival rates in recipients with nonvascularized and noninflamed graft beds, survival rates significantly decline (under 50%) when grafts are placed onto vascularized or inflamed host beds associated with conditions such as previous graft rejection, infection, or trauma. These results are seen despite treatment with high doses of nonspecific immunosuppressive medications, which often do not promote long-term survival.Therefore, new strategies are required to modulate the immune system without conventional immunosuppressive agents and improve transplant survival in "high-risk" patients with inflamed host beds. Regulatory T-cells (Treg) are key modulators of the immune response and may play a crucial role in a new therapy for high-risk corneal transplantation.Here we introduce the murine high-risk corneal transplantation model and review the implications of Tregs for corneal transplantation.Key words: corneal transplantation, regulatory T-cell, high-risk corneal transplantation, neovascularization Introduction Outline of corneal transplantationThe first corneal transplantation was successfully performed by Dr. Eduard Zirm in 1905 1) . Along with the growing demand for corneal transplantation, the first institutional eye bank was born in New York in 1944. In Japan, the first eye bank was established by Juntendo University School of Medicine and Keio University in 1963. Nowadays, cornea transplantation is one of the most frequently performed solid organ transplantation worldwide with 65,000 cases annually. There are more than 40,000 cases in the US and 1,500 cases in Japan annually 2) .The cornea is the transparent, dome shaped layer that covers the anterior eye and has the dual function of protecting the inner contents of the eye as well as providing approximately two thirds of the eyeʼs refractive power. The cornea has three layers, including the epithelium, stroma and endothelium, divided by Bowmanʼ s membrane and Descemetʼ s membrane respectively. Corneal transplantation is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue. Corneal transplantation has evolved into an array of techniques focused on the selective replacement of diseased layers of the cornea such as lamellar corneal transplantation, Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty. These procedures are tailored specifically to the underlying pathologic condition causing the corneal dysfunction. However, the majority of corneal transplantations are still penetrating keratoplasties . In all forms of transplantation, certain hosts are known to be at particularly high risk for graft rejection. High-risk transplant recipients often abruptly and irreversibly reject their grafts regardless of the magnitude of immunosuppression. Thus, understanding the underlying mechanisms of high rejection rates in high-risk corneal transportation is essential fo...

show abstract

“…Tregs function to downregulate the efferent phase of the delayed-type hypersensitivity response, contributing to the phenomenon of anterior chamber-associated immune deviation (ACAID) [106]. ACAID describes the aberrant systemic immune response induced when antigens enter the anterior chamber [110].…”

Section: Tregs In Corneal Transplantationmentioning

confidence: 99%

Review: The function of regulatory T cells at the ocular surface

et al. 2017

Self Cite

View full text Add to dashboard Cite

Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface. Finally, we review the role of Tregs in promoting allotolerance in corneal transplantation.

show abstract

Alloimmunity and Tolerance in Corneal Transplantation

Cited by 107 publications

References 101 publications

Management of high-risk corneal transplantation

Management of high-risk corneal transplantation

A New Immunotherapy Using Regulatory T-Cells for High-Risk Corneal Transplantation

Review: The function of regulatory T cells at the ocular surface

Contact Info

Product

Resources

About