Unlike blood vessels which have been studied extensively in the past, lymphatic vessel research represents an explosive field of new discovery owing to the recent identification of several lymphatic specific markers. The cornea provides an ideal tissue for vascular studies due to its accessible location, transparent nature, and vessel-free and -inducible characters.
Once induced, corneal lymphatic vessels enhance high volume delivery of antigens and immune cells, and accelerate corneal inflammation and transplant rejection. Our primary long-term goal is to use corneal models to elucidate molecular mechanisms of lymphatic vessel development, and their applications to lymphatic-related diseases both inside and outside of the eye; a necessary prerequisite to the development of new therapeutic protocols.
Research on corneal lymphatic vessels has broader clinical implications beyond the treatment of ocular diseases alone, since the lymphatic network penetrates most tissues in the body, and its dysfunctions are involved in a diverse array of disorders including cancer metastasis, diabetes, delayed wound healing, autoimmune diseases, and lymphedema (primary or secondary to radiation therapies), among many others.
Chen L, Huq S, Gardner H, de Fougerolles AR, Barabino S, Dana MR. Very late antigen (VLA)-1 blockade leads to marked survival of corneal allografts. Arch. Ophthalmol. 2007; 125:783-788.
Jin Y, Shen L, Chong EM, Hamrah P, Zhang Q, Chen L, Dana MR. The chemokine receptor CCR7 mediates corneal antigen-presenting cell trafficking. Molecular Vision 2007; 13:626-634.
Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana MR. Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Ocul. Immunol. Inflamm. 2007; 15:275-278.
Cursiefen C, Chen L, Hamrah P, Pytowski B, Persaud K, Wu Y, Jackson D, Streilein JW, Dana MR. High constitutive expression of VEGFR-3 by corneal epithelium maintains corneal avascularity by serving as decoy receptor. Proc. Natl. Acad. Sci. USA. 2006; 103:11405-11410.
Chen L, Cursiefen C, Barabino S, Zhang Q, Streilein JW, Dana MR. Novel expression and characterization of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) by conjunctival cells. Invest. Ophthalmol. Vis. Sci. 2005; 46:4536-4540.
Barabino S, Shen L, Chen L, Rolando M, Dana R. The controlled environment chamber: a new model for dry eyes. Invest. Ophthalmol. Vis. Sci. 2005; 46:2766-2771.
Cursiefen C, Ikeda S, Smith RS, Jackson D, Mo JS, Chen L, Pytowski B, Dana MR, Streilein JW. Spontaneous corneal hem- and lymphangiogenesis with destrin-mutation depend on VEGFR3-signaling. Am. J. Pathol. 2005; 166:1367-1377.
Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana MR. Vascular endothelial growth factor receptor-3 (VEGFR-3) mediates dendritic cell migration to lymph nodes and induction of immunity to corneal transplants. Nat. Med. 2004; 10:813-815.
Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D'Amore PA, Dana MR, Wiegand SJ, Streilein JW. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Invest. 2004; 113:1040-1050.
Hamrah P, Chen L, Cursiefen C, Zhang Q, Joyce NC, Dana MR. Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) on monocytic bone marrow-derived cells in the conjunctiva. Exp. Eye. Res. 2004; 79:553-561.
Cursiefen C, Cao J, Chen L, Liu Y, Maruyama K, Jackson D, Kruse FE, Wiegand SJ, Dana MR, Streilein JW. Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival. Invest. Ophthalmol. Vis. Sci. 2004; 45:2666-2673.
Hamrah P, Chen L, Zhang Q, Dana MR. Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells. Am. J. Pathol. 2003; 163:57-68.
Cursiefen C, Chen L, Dana MR, Streilein JW. Corneal lymphangiogenesis: evidence, mechanisms, and implications for corneal transplant immunology. Cornea. 2003; 22:273-281.
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