Abstract
Purpose:
The lymphatic pathway is a major mediator for transplant rejection. Most recently, we have provided the first evidence on lymphatic valve formation during corneal inflammatory lymphangiogenesis (Truong et al. 2011). The purpose of this real-time in vivo study is to investigate the time course and pattern of lymphangiogenesis as well as lymphatic valve formation induced by corneal transplantation with our newly developed live imaging system and Prox-1-GFP mice.
Methods:
Standard orthotopic corneal transplantation was performed with Prox1-GFP mice as recipients. Corneal grafts of the same mice were continuously observed by the live imaging system for longitudinal analysis. Prox-1 positive lymphatic vessels and valves were evaluated at both limbal and corneal areas.
Results:
Prox-1 positive lymphatic vessels and valves were formed after corneal transplantation. As corneal lymphangiogenesis proceeded, more valves were observed inside vessel cavities. Furthermore, lymphatic valvulogenesis was initiated inside limbal vessels before spreading into the central cornea.
Conclusions:
We have shown, for the first time, corneal transplantation induces both lymphangiogenesis and valvulogenesis in vivo and in real time. Further investigation on this new phenomenon may reveal new mechanisms underlying transplant rejection. Since the lymphatic system plays an important role in many other functions, this study may also offer new insights to our understanding and treatment of other lymphatic related disorders outside the eye.
Keywords: 480 cornea: basic science •
741 transplantation •
609 neovascularization