Center for Eye Disease & Development, Program in Vision Science, UC Berkeley School of Optometry.
Vision Science 212G. Molecular Genetics of Vertebrate Eye Development and Diseases
Introduction for graduate students to general molecular genetics of vertebrate eye development and related major diseases; basic principles of molecular and cell biology; commonly used techniques and experimental approaches; and biological mechanisms of eye development and disorder
Vision Science 206A. Anatomy and Physiology of the Eye and Visual System
Anatomical structures and physiological functions of ocular tissues; patho-physiology of various ocular disease processes; basic concepts in medical approaches to ocular diseases
Vision Science 206D. Neuroanatomy and Neurophysiology of the Eye and Visual System
Structure and function of the neurosensory retina, photoreceptors, RPE including blood supply. Current concepts of etiology and management of major retinal conditions. Overview of diagnostic techniques in retinal imaging, electrophysiologic testing and new genetic approaches. Structure and function of the early visual pathway including retinal ganglion cells, optic nerves, lateral geniculate nucleus and visual cortex. Pupillary responses. Specialization in the visual cortex.
Vision Science 212D. Anatomy and Vegetative Physiology of the Eye
Introduction for graduate students to a general survey of all components of the eye and orbit; vegetative physiology of the cornea and tear film, aqueous humor, crystalline lens, uveal tract, and retina
Lymph and Blood Vascular Biology, Corneal Inflammation, Transplantation Immunity, Glaucoma
Our research focuses on molecular and cellular mechanisms of ocular inflammation and immunity, particularly those involved in lymphatic and blood vessel development and regulation. Unlike blood vessels which have been studied extensively in the past, lymphatic research represents an explosive field of new discovery owing to the identification of several lymphatic specific markers and the advancement in technology. The cornea provides an ideal tissue for vascular studies due to its accessible location, transparent nature, and vessel-free and vessel-inducible features. Once induced, corneal lymphatic vessels enhance high volume delivery of antigens and immune cells, and accelerate inflammation and transplant rejection. Our primary long-term goal is to elucidate the basic molecular and cellular mechanisms underlying lymphatic vessel development and to discover novel therapeutic targets for lymphatic-related diseases inside and outside of the eye.
Research on corneal lymphatic vessels has broad clinical implications. For example, we have recently discovered that the Schlemm’s canal, a critical structure of aqueous humor outflow pathway, possesses lymphatic features. Further investigation on this novel phenomenon promises for divulging new mechanisms and therapeutic strategies for glaucoma, a major cause of blindness in the world. Moreover, the lymphatic network penetrates most tissues in the body, and its dysfunctions have been found in a diverse array of disorders, which include but are not limited to cancer metastasis, diabetes, obesity, lymphedema, and inflammatory, infectious and immune diseases.
Zhang LW, Li GY, Shi M, Liu HH, Ge SK, Ou Y, Flanagan J, Chen L. Establishment and characterization of an acute model of ocular hypertension by laser-induced occlusion of episcleral veins. Invest Ophthalmol Vis Sci. 2017; 58:3879-3886.
Wang D, Wu F, Yuan H, Wang A, Kang GJ, Truong T, Chen L, McCallion AS, Gong X, Li S. Sox10+ cells contribute to vascular development in multiple organs. Arterioscler Thromb Vasc Biol. 2017; 37:1727-1731.
Sessa R, Chen L. Lymphangiogenesis – a new player in herpes simplex virus 1 triggered T cell response. Immunol. Cell Biol. 2017; 95(1):5-6. Invited Commentary Article by the Editor.
Zhang L, Li G, Sessa R, Kang GJ, Shi M, Ge S, Gong AJ, Wen Y, Chintharlapalli S, Chen L. Angiopoietin-2 blockade promotes survival of corneal transplants. Invest Ophthalmol Vis Sci. 2017; 58:79-86.
Sessa R, Yuen D, Wan S, Roster M, Padmanaban P, Ge S, Smith A, Fletcher R, Baudhuin-Kessel A, Yamaguchi TP, Lang RA, Chen L. Monocyte-derived Wnt5a regulates Inflammatory lymphangiogenesis. Cell Research. 2016; 26:262-5.
Kang GY, Ecoiffier E, Truong T, Yuen D, Li G, Lee N, Zhang L, Chen L. Intravital imaging reveals dynamics of lymphangiogenesis and valvulogenesis. Scientific Reports. 2016; 6:19459.
Kang GY, Truong T, Huang E, Su V, Ge S, Chen L. Integrin alpha 9 blockade suppresses lymphatic valve formation and promotes transplant survival. Invest Ophthalmol Vis Sci. 2016; 57(14):5935–5939.
Grimaldo S, Yuen D, Theis J, Ng M, Ecoiffier T, Chen L. MicroRNA-184 regulates corneal lymphangiogenesis. Invest Ophthalmol Vis Sci. 2015; 56:7209-7213.
Altiok E, Ecoiffier T, Sessa R, Yuen D, Grimaldo S, Tran C, Li D, Rosner M, Lee N, Uede T, Chen L. Integrin alpha-9 mediates lymphatic valve formation in corneal lymphangiogenesis. Invest Ophthalmol Vis Sci. 2015; 56:6313-6319.
Heindl LM, Kaser-Eichberger A, Schlereth SL, Bock F, Regenfuss B, Reitsamer HA, McMenamin P, Lutty GA, Maruyama K, Chen L, Dana R, Kerjaschki D, Alitalo K, De Stefano ME, Junghans BM, Schroedl F, Cursiefen C. Sufficient Evidence for Lymphatics in the Developing and Adult Human Choroid? Invest Ophthalmol Vis Sci. 2015; 56:6709-6710.
Iolyeva M, Aebischer D, Proulx,ST, Willrodt AH, Ecoiffier T, Häner S, Bouchaud G, Krieg C, Onder L, Ludewig B, Santambrogio L, Boyman O, Chen L, Finke D, Halin C. Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage. Blood, 2013; 122:2271-2281.
Yuen D, Grimaldo S, Sessa R, Ecoiffier T, Truong T, Huang E, Bernas M, Daley S, Witte M, Chen L. Role of angiopoietin-2 in corneal lymphangiogenesis. Invest Ophthalmol Vis Sci. 2014; 55:3320-3327.
Bianchi R, Fischer E, Yuen D, Ernst E, Chen L, Otto VI, Detmar M. Mutation of threonin 34 in mouse podoplanin-Fc reduces CLEC-2 binding and toxicity in vivo while retaining anti-lymphangiogenic activity. J Biol Chem. 2014; 289:21016-21027.
Falk Schroedl, Alexandra Kaser-Eichberger, Simona Schlereth, Felix Bock, Birgit Regenfuss, Herbert Reitsamer, Gerard Lutty, Kazuichi Maruyama, Lu Chen, Elke Luetjen-Drecoll, Reza Dana, Dontscho Kerjaschki, Kari Alitalo, Maria Egle De Stafano, Barbara Junghans, Ludwig Heindl, Claus Cursiefen. Consensus statement on the immunohistochemical detection of ocular lymphatic vessels. Invest Ophthalmol Vis Sci. 2014; 55:6640-6642.
Truong TN, Li H, Hong YK, Chen L. Novel characterization and live imaging of Schlemm’s canal expressing Prox-1. PLoS One. 2014; 9:e98245.
Truong T, Huang E, Yuen D, Chen L. Corneal lymphatic valve formation in relation to lymphangiogenesis. Invest Ophthalmol Vis Sci. 2014; 55:1876-1883.
Choi I, Lee YS, Chung HK, Choi D, Ecoiffier T, Lee HN, Kim KE, Lee S, Park EK, Maeng YS, Kim NY, Ladner RD, Petasis NA, Koh CJ, Chen L, Lens HJ, Hong YK. Interleukin-8 can reduce post-surgical lymphedema formation by promoting lymphatic vessel regeneration. Angiogenesis. 2013; 16:29-44.
Schulz MMP, Reisen F, Zgraggen S, Fischer S, Yuen D, Kang GJ, Chen L, Schneider G, Detmar M. Phenotype-based high-content chemical library screening identifies novel inhibitors of in vivo lymphangiogenesis. Proc. Natl. Acad. Sci. USA. 2012; 109:E2665-74.
Yuen D, Wu X, Kwan AC, LeDue J, Zhang H, Ecoiffier T, Pytowski B, Chen L. Live imaging of newly formed lymphatic vessels in the cornea. Cell Research. 2011; 21:1745–1749.[Article published with Research Highlight at Swiss Federal Institute of Technology by Proulx ST and Detmar M. “Watching Lymphatic Vessels Grow by Making Them Flow”. Cell Research 2011 (1-2). doi: 10.1038/cr.2011.191.]
Choi I, Lee S, Chung HK, Lee YS, Kim KE, Choi D, Park EK, Yang D, Ecoiffier T, Monahan J, Chen W, Aguilar B, Lee HN, Yoo J, Koh CJ, Chen L, Wong AK, Hong YK. 9-cis retinoic acid promotes lymphangiogenesis and enhances lymphatic vessel regeneration: therapeutic implications of 9-cis retinoic acid for secondary lymphedema. Circulation. 2012; 125:872-882.[Article published with Editorial comment by Cooke JP at Stanford Cardiovascular Institute. “Lymphangiogenesis: A Potential New Therapy for Lymphedema?” Circulation. 2012; 125:853-855. doi: 10.1161/CIRCULATIONAHA.111.083477.]
Ecoiffier T, Sadovnikova A, Yuen D, Chen L. Conjunctival lymphatic response to corneal inflammation. J. Ophthalmol. J. Ophthalmol. 2012;2012:953187.]
Truong T, Altiok EI, Yuen D, Ecoiffier T, Chen L. Novel characterization of lymphatic valve formation during corneal inflammation. PLoS One. 2011; 6 (7): e21918.
Yuen D, Leu R, Sadovnikova A, Chen L. Increased lymphangiogenesis and hemangiogenesis in infant cornea. Lym. Res. Biol. 2011; 9:109-114.
Zhang H, Grimaldo S, Yuen D, Chen L. Combined blockade of VEGFR-3 and VLA-1 markedly promotes high-risk transplant survival. Invest. Ophthalmol. Vis. Sci. 2011; 52:6529-6535.
Grimaldo S, Yuen D, Ecoiffier T, Chen L. Very Late Antigen-1 mediates corneal lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2011; 52:4808-4812.
Yuen D, Pytowski B, Chen L. Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages. Invest. Ophthalmol. Vis. Sci. 2011; 52:2593-2597.
Zhang H, Hu X, Tse J, Tilahun F, Qiu M, Chen L. Spontaneous lymphatic vessel formation and regression in the cornea. Invest. Ophthalmol. Vis. Sci. 2011; 52:334-338.
Chen L, Hann B, Wu L. Experimental models to study lymphatic and blood vascular metastasis, in “From local invasion to metastatic cancer”. Stanley P.L. Leong (Editor), Humana Press. 2011.
Cueni LN, Chen L, Zhang H, Marino D, Huggenberger R, Alitalo A, Bianchi R, Detmar M. Podoplanin-Fc reduces lymphatic vessel formation in vitro and in vivo and causes disseminated intravascular coagulation when transgenically expressed in the skin. Blood. 2010, 116:4376-4384.[Article published with Comment by Kim H and Koh GY at Korea Advanced Institute of Science and Technology. “Podoplanin-Fc burns out platelets.” Blood. 2010; 116:4043-4044.]
Grimaldo S, Garcia M, Zhang H, Chen L. Specific role of lymphatic marker podoplanin in retinal pigment epithelial cells. Lymphology. 2010; 43:128-134.]
Zhang H, Tse J, Hu X, Witte M, Bernas M, Kang J, Tilahun F, Hong YK, Qiu M, Chen L. Novel discovery of LYVE-1 expression in the hyaloid vascular system. Invest. Ophthalmol. Vis. Sci. 2010; 51:6157-6161.
Ecoiffier T, Yuen D, Chen L. Differential distribution of blood and lymphatic vessels in the cornea. Invest. Ophthalmol. Vis. Sci. 2010; 51:2436-2440.
Dietrich T, Bock F, Yuen D, Hos D, Bachmann B, Zahn G, Wiegand S, Chen L, Cursiefen C. Cutting edge: Lymphatic vessels, not blood vessels, primarily mediate immune rejections after transplantation. J. Immunol. 2010; 184:535-539.
Chen L. Ocular Lymphatics: State-of-the-Art Review. Lymphology. 2009; 42:66-76. Invited review.
Chung ES, Chauhan S, Jin Y, Zhang Q, Nakao S, Chen L, Dana R. Contribution of macrophages to angiogenesis induced by VEGFR-3 specific ligands. Am. J. Pathol. 2009; 175:1984-1992.
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.
Mower GD, Chen L. Laminar distribution of NMDA receptor subunit (NR1, NR2A, NR2B) expression during the critical period in visual cortex. Brain Res. Mol. Brain Res. 2003; 119:19-27.
Chen L, Yang C, Mower GD. Developmental changes in the expression of GABA-A receptor subunits (α1, α2, α3) during postnatal development of the visual cortex. Brain Res. Mol. Brain Res. 2001; 88:135-43.
Chen L, Cooper NGF, Mower GD. Subunit compositional changes of NMDA receptors during postnatal development of the visual cortex. Brain Res. Mol. Brain Res. 2000; 78:196-200.