Dr. Chen’s research mainly focuses on defining molecular and cellular mechanisms of corneal inflammation and transplantation immunity, particularly those related to lymphatic and blood vessel formation and regulation. Not present in normal adult cornea, lymphatic and blood vessels are induced into this tissue after an inflammatory, infectious, immunogenic, traumatic, or chemical insult. These vessels enhance high volume delivery of antigens and inflammatory and immune cells, and accelerate corneal pathogenesis such as inflammation, dry eye, and transplant rejection. Our long-term goal is to elucidate the basic mechanisms underlying the pathologic vascular events and to identify new targets for therapeutic intervention. Results from our corneal studies are applicable to broad vascular diseases occurring outside the eye as well.
Multiple projects are aimed to define the molecular and cellular mechanisms underlying pathologic lymphangiogenesis, angiogenesis, and transplant rejection using an assortment of in vitro, in vivo and in real time approaches and models. We have shown that corneal lymphangiogenesis and angiogenesis are complex processes orchestrated by a number of factors and have identified several new potential targets for therapeutic development.
We recently reported a novel finding that the cornea is not devoid of lymphatic vessels from embryogenesis. Spontaneous lymphatic formation and regression occurs in this tissue before it matures and becomes transparent. Given that lymphangiogenesis can be reactivated in adult cornea upon pathologic insults, the cornea is the first tissue ever identified to possess a full range of lymphatic plasticity. Further investigation is undertaken to reveal fundamental mechanisms underlying this novel phenomenon.
We recently reported another novel finding that corneal lymphatics develop luminal valves as lymphangiogenesis progresses. These valves may serve as a maturation marker for lymphatic development and they function to direct proper lymph flow in diseased cornea. Further investigation is undertaken to assess their anatomical features and functional roles in inflammatory and immune responses.
The cornea provides an ideal tissue for vascular imaging due to its accessible location and transparent nature. We have recently developed a new and highly advanced technology for live imaging of both lymphatic and blood vessels in the cornea. This real-time in vivo technology enables 4-D detection of dynamic vascular events at cellular level. The system has great advantages and allows for longitudinal follow-up of the same subject over a short or long period of time. Both time-lapse images and videos can be taken from low to high magnification and along various axes for data analysis. It is being used in multiple projects to study dynamic processes of lymphangiogenesis, angiogenesis, and valvulogenesis in various pathological settings.