Project Details
Projekt
Induction of corneal transplant tolerance by anti(lymph)angiogenic therapy
Subject Area
Ophthalmology
Term
from 2015 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 257498687
Corneal transplantation is the most common form of transplantation. Immune reactions are the main complication after grafting, especially when performed into pathologically hem- and lymphvascularized, so called high-risk recipient eyes. In the murine model of high-risk transplantation, partly reflecting immune competent tissue transplantations elsewhere, we could show that blockade of inflammatory lymphangiogenesis and migration of antigen presenting cells in the high-risk induction phase by systemic depletion of VEGF-A induces graft tolerance. Since in the clinic most high-risk eyes already contain lymphatic vessels prior to transplantation, we established several novel (lymph)angioregressive therapies (such as fine needle diathermy and photodynamic therapy). Using these innovative tools we validated the novel treatment concept of temporary, selective, preoperative lymphangioregression at graft site to promotesubsequent graft survival. Based on these findings and since all immunomodulatory approaches in high-risk eyes so far only achieve partial (albeit significant) survival improvements, we want to develop novel improved techniques of combined antilymphangiogenesis of both donor and host and try to transfer that approach to extraocular sites. The new project has two specific aims: 1) to analyze the graft-promoting effect of local VEGF-A depletion in the donor by anti-VEGF preconditioning combined with preoperative lymphangioregression of the host and postoperative antilymphangiogenesis in both host and donor (“novel triple approach”) and 2) totranslate the novel concept of antilymphangiogenic/lymphangioregressive pre-treatment of the host and donor tissue to extraocular sites, starting with tissues (skin). The results of this project will provide novel methods to improve graft survival, both in the eye but also beyond.
DFG Programme
Research Units
