Regeneration of lymphatic vessels after lymphatic-specific photodynamic therapy is not dependent on lymphangiogenesis and tissue remodeling by myofibroblast

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Photodynamic therapy (PDT) is a clinically used therapeutic procedure based on the administration of a non-toxic photosensitizer followed by sub-thermal light exposure for treatment of pathologic cornea neovascularization. However, this approach does not target pre-existing lymphatics at the cornea limbus and sustained antigen drainage can lead to rejection of allogenic cornea grafts. Our PDT protocol aim at specific destruction of lymphatic vessels leaving blood circulation intact. Collecting lymphatic vessels remain occluded for 9 days and then the drainage is restored. Interestingly, lymphatic regeneration occurs not by lymphangiogenesis and wound healing but by true, epimorphic regeneration. We found that myofibroblasts were present in the tissue even though the tissue injury was limited to the lymphatic endothelial cells of collecting lymphatics and their pericyte coverage. Even though myofibroblasts were recruited and persisted in the tissue for the whole period of lymphatic regeneration no scaring in other tissue structures was observed, i.e. remodeling of blood vessels, nerve fibers or adipocytes. Limited tissue remodeling and scarification after lymphatic-specific PDT should alleviate potential clinical translation of this method for temporal occlusion of collecting lymphatics e.g. before cornea grafting.

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