Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology

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 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.

Ex Vivo–Induced Bone Marrow-Derived Myeloid Suppressor Cells Prevent Corneal Allograft Rejection in Mice

“…During the process of rejection, lymphatic vessels and neovascular tissues are important factors that support the immune and inflammation response, as donor antigens, inflammatory cells, and pro-inflammatory cytokines could be delivered through these vessels to the graft. For corneal graft survival, reducing neovascularization and lymphangiogenesis is vital, 43 , 44 and such reduction was confirmed in our high-risk mouse corneal grafts.…”

Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis

“…Our results showed that TNF-α, IFN-γ, IL-1β, and IL-2 levels in the aqueous humor of keratoplasty rejection cases were much higher than those in cases where the grafts survived [129][130][131][132][133] (Figure 6). Finally, as in other tissues beyond the eye, the homeostatic equilibrium of the ocular surface is critically maintained by complex and heterogeneous parainflammatory mechanisms [138][139][140]. Cross-talk between APCs, T cells, and various other immune cells plays a central role in corneal graft tolerance (Figure 7).…”

“…Finally, as in other tissues beyond the eye, the homeostatic equilibrium of the ocular surface is critically maintained by complex and heterogeneous parainflammatory mechanisms [138][139][140]. Cross-talk between APCs, T cells, and various other immune cells plays a central role in corneal graft tolerance (Figure 7).…”

Topical Administration of the Kappa Opioid Receptor Agonist Nalfurafine Suppresses Corneal Neovascularization and Inflammation

“…CNV occurs as a result of an imbalance between angiogenic and anti-angiogenic factors in favour of angiogenic molecules [29][30][31][32] . This imbalance causes pathogenic angiogenesis in CNV, which in turn activates pro-angiogenic factors including VEGF, VEGFR, and IFN-γ in the neovascularized microenvironment and strongly potentiates further development of CNV 21,33 .…”