Abstract

The cornea is the most densely innervated tissue in humans. Peripheral corneal nerves regenerate follow injury. Our hypothesis is that VEGF is a critical determinant of corneal nerve regeneration after injury and that the signaling pathways which mediate neurogenesis are distinct from those which mediate angiogenesis.
Aim A will characterize the expression of VEGF and VEGF receptors and identify the receptors which mediate VEGF-dependent neurogenesis in vitro and in vivo.
Aim B will characterize effect of VEGF on the regeneration of nerves in 2 injury models, while Aim C will investigate the pathways responsible for these effects. We will analyze whether there exists a differential activation of VEGF mediated neurogenesis following different injuries.

Public Health Relevance

Proper regeneration of corneal nerves after injury is needed to prevent the development of potentially blinding neurotrophic keratitis. This application will investigate a new role in corneal nerve regeneration for the well characterized VEGF signaling pathway in order to develop new techniques for promoting corneal repair.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018594-04
Application #
8511655
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Mckie, George Ann
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$401,375
Indirect Cost
$163,875

  Institution

Name
Weill Medical College of Cornell University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Hirata, Harumitsu; Dallacasagrande, Valentina; Mizerska, Kamila et al. (2018) Ambient Air Currents Activate Corneal Nerves During Ocular Desiccation in Rats: Simultaneous Recordings of Neural Activity and Corneal Temperature. Invest Ophthalmol Vis Sci 59:4031-4043
Hirata, Harumitsu; Mizerska, Kamila; Dallacasagrande, Valentina et al. (2017) Estimating the Osmolarities of Tears During Evaporation Through the ""Eyes"" of the Corneal Nerves. Invest Ophthalmol Vis Sci 58:168-178
Yang, Jessica F; Walia, Amit; Huang, Yu-hui et al. (2016) Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions. Surv Ophthalmol 61:272-96
Zhu, Jimmy; Dugas-Ford, Jennifer; Chang, Michael et al. (2015) Simultaneous in vivo imaging of blood and lymphatic vessel growth in Prox1-GFP/Flk1::myr-mCherry mice. FEBS J 282:1458-1467
Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F et al. (2015) Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity. Invest Ophthalmol Vis Sci 56:8125-40
Wang, Yvonne; Kornberg, Daniel L; St Clair, Ryan M et al. (2015) Corneal nerve structure and function after long-term wear of fluid-filled scleral lens. Cornea 34:427-32
Walia, Amit; Yang, Jessica F; Huang, Yu-Hui et al. (2015) Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications. Biochim Biophys Acta 1850:2422-38
Guaiquil, Victor H; Pan, Zan; Karagianni, Natalia et al. (2014) VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions. Proc Natl Acad Sci U S A 111:17272-7
Hirata, Harumitsu; Rosenblatt, Mark I (2014) Hyperosmolar tears enhance cooling sensitivity of the corneal nerves in rats: possible neural basis for cold-induced dry eye pain. Invest Ophthalmol Vis Sci 55:5821-33
Kim, Charles; Barbut, Denise; Heinemann, Murk H et al. (2014) Synthetic neurotensin analogues are nontoxic analgesics for the rabbit cornea. Invest Ophthalmol Vis Sci 55:3586-93

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