Abstract
(Lymph)angiogenesis into the cornea prior to and after corneal transplantation is a critical risk factor for allograft rejection. Lymphatic vessels even more than blood vessels seem important in mediating immune responses, as they facilitate allograft sensitization in the draining lymph nodes. Thus, the concept of modulating lymphatic trafficking to promote corneal graft survival seems promising. A variety of approaches has been developed to inhibit progressive lymphangiogenesis in experimental settings. Recently, additionally to pharmacological approaches, clinically available techniques such as UVA-based corneal collagen crosslinking and fine needle diathermy were reported to be effective in regressing lymphatic vessels and to experimentally promote graft survival. Clinical pilot studies also suggest the efficacy of blocking antigen presenting cell trafficking to regional lymph nodes by regressing corneal lymphatic vessels to enhance allograft survival in high-risk eyes. In this article, we will give an overview of current strategies to modulate lymphatic trafficking with a special focus on recently reported strategies, which may be easy to translate into clinical practice. This novel concept of temporary, pretransplant regression of lymphatic vessels at the site of transplantation to promote subsequent corneal transplant survival (“lymphangioregressive preconditioning”) may also be applicable to other transplantation sites later.
Highlights
The transparent cornea is one of the few avascular tissues of the body
We have previously demonstrated experimentally that corneal grafts transplanted into recipient beds that contain pathological corneal blood vessels but not lymphatic vessels, resulted in allograft survival rates that were comparable to survival rates in completely avascular recipients
Since we and others could show that (1) pathologic corneal lymphatic vessels act as conduits for antigen presenting cells (APCs) trafficking from donor tissue to host regional lymph nodes, (2) that inhibition of lymphangiogenesis prior to and after transplantation leads to improved graft survival, and (3) that a temporary blockade or regression of corneal lymphatic vessels is sufficient to prevent corneal allosensitization, we developed the novel therapeutic concept of “temporary preoperative lymphangioregression at the recipient site to promote subsequent corneal transplant survival” [9,21,22,23,24,25,59,83,84,85,86,87,88,89,90,91,92,93]
Summary
The transparent cornea is one of the few avascular tissues of the body. Corneal avascularity, which is known as the corneal “(lymph)angiogenic privilege”, is crucial for its transparency and thereby visual acuity [1]. The most commonly performed type of keratoplasty is replacement of the full thickness of the cornea (variant 1 [41]) Here, the rejection rate strongly correlates with the vascular status prior to transplantation, being low in avascular recipient beds and high in pathologically prevascularized recipient beds. Pathological corneal lymphatic as well as blood vessels are crucially involved in immune-mediated allograft rejection and dramatically decrease survival rates of corneal transplants [47,51,52]. We have previously demonstrated experimentally that corneal grafts transplanted into recipient beds that contain pathological corneal blood vessels but not lymphatic vessels (which was achieved by pharmacological blockade of lymphangiogenesis), resulted in allograft survival rates that were comparable to survival rates in completely avascular recipients. We discuss the novel concept of promotion of corneal transplant survival by modulating lymphatic trafficking (“lymphangioregressive preconditioning of the host site”)
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