Claus Cursiefen

Corneal opacities are the second most common cause of blindness worldwide. Corneal transplantation is the main therapeutic procedure against corneal blindness. Immunological rejection remains the main reason for graft failure worldwide. The risk of an immune reaction depends decisively on the preoperative situation of the recipient: if it is, as in the normal case, free of vessels and low in inflammation ("corneal angiogenic and immune privilege“), immune rejections are rare both in the mouse model of corneal transplantation and in the patient. However, if pathological inflammation or neovascularization of the cornea is present, the risk of rejection increases to more than 50% ("high-risk situation“). This concerns especially patients in so-called "lower and middle-income countries“ (LMICs). We could show that pathological blood vessels and even more so clinically invisible pathological lymphatic vessels sprouting into the cornea are crucial for the increased risk of rejections after corneal transplantation. Targeted blockade of corneal lymphangiogenesis or temporary lymphangioregression preoperatively reduced graft rejection in the well-characterized mouse model of corneal transplantation. Lymphangioregressive approaches include, as described by us for the first time, the destruction of lymphatic vessels by UVA-light-associated crosslinking, via photodynamic therapy or monopolar vascular cauterization. Here, further molecular experimental but also translational clinical studies are needed to translate this novel concept of temporary perioperative lymphangioregression to the clinic and improve graft survival. This novel concept may also help prevent solid organ graft rejections.