OBJECTIVE: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. METHODS: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b(+)/LYVE-1(+) monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II(hi)) antigen-presenting cells to the lymphoid compartment. RESULTS: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P < .001) and lymphatic caliber (P < .02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b(+)/LYVE-1(+) monocytic cells to the cornea and homing of mature CD11b(+) antigen-presenting cells to the draining lymph nodes were also associated with DED. CONCLUSION: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.
OBJECTIVE: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. METHODS:Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b(+)/LYVE-1(+) monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II(hi)) antigen-presenting cells to the lymphoid compartment. RESULTS: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P < .001) and lymphatic caliber (P < .02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b(+)/LYVE-1(+) monocytic cells to the cornea and homing of mature CD11b(+) antigen-presenting cells to the draining lymph nodes were also associated with DED. CONCLUSION: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.
Authors: Balamurali K Ambati; Miho Nozaki; Nirbhai Singh; Atsunobu Takeda; Pooja D Jani; Tushar Suthar; Romulo J C Albuquerque; Elizabeth Richter; Eiji Sakurai; Michael T Newcomb; Mark E Kleinman; Ruth B Caldwell; Qing Lin; Yuichiro Ogura; Angela Orecchia; Don A Samuelson; Dalen W Agnew; Judy St Leger; W Richard Green; Parameshwar J Mahasreshti; David T Curiel; Donna Kwan; Helene Marsh; Sakae Ikeda; Lucy J Leiper; J Martin Collinson; Sasha Bogdanovich; Tejvir S Khurana; Masabumi Shibuya; Megan E Baldwin; Napoleone Ferrara; Hans-Peter Gerber; Sandro De Falco; Jassir Witta; Judit Z Baffi; Brian J Raisler; Jayakrishna Ambati Journal: Nature Date: 2006-10-18 Impact factor: 49.962
Authors: Jerry Y Niederkorn; Michael E Stern; Stephen C Pflugfelder; Cintia S De Paiva; Rosa M Corrales; Jianping Gao; Karyn Siemasko Journal: J Immunol Date: 2006-04-01 Impact factor: 5.422
Authors: Falk Schroedl; Alexandra Kaser-Eichberger; Simona L Schlereth; Felix Bock; Birgit Regenfuss; Herbert A Reitsamer; Gerard A Lutty; Kazuichi Maruyama; Lu Chen; Elke Lütjen-Drecoll; Reza Dana; Dontscho Kerjaschki; Kari Alitalo; Maria Egle De Stefano; Barbara M Junghans; Ludwig M Heindl; Claus Cursiefen Journal: Invest Ophthalmol Vis Sci Date: 2014-10-14 Impact factor: 4.799
Authors: Jin Woo Kwon; Yeon Woong Chung; Jin A Choi; Tae Yoon La; Dong Hyun Jee; Yang Kyung Cho Journal: Int J Ophthalmol Date: 2016-02-18 Impact factor: 1.779
Authors: Shilpa Kodati; Sunil K Chauhan; Yihe Chen; Thomas H Dohlman; Parisa Karimian; Daniel Saban; Reza Dana Journal: Invest Ophthalmol Vis Sci Date: 2014-08-19 Impact factor: 4.799
Authors: Marjan Farid; Anshu Agrawal; Daniel Fremgen; Jeremiah Tao; He Chuyi; Anthony B Nesburn; Lbachir BenMohamed Journal: Ocul Immunol Inflamm Date: 2014-12-23 Impact factor: 3.070