Abstract

The corneal endothelium functions as a barrier to fluid movement into the cornea and maintains the transparency of the cornea. Human corneal endothelial cells (CEC), like neuronal cells, essentially do not regenerative in vivo. Just as the survival of neurons is promoted by neurotrophic factors, the survival of CEC may also be promoted by trophic factors. Ciliary neurotrophic factor (CNTF) was discovered and originally isolated from an extract of eye tissues consisting of ciliary body, iris, and choroid. CNTF induces in neurons the expression of the gene for VIP, a neuropeptide that also shows neurotrophic activities. In donor human, preliminary studies showed that VIP-immunoreactivities and VIP mRNA are present in the CEC, that both CNTF and VIP receptors are expressed in CEC, that CNTF is expressed in the cornea, and that the VIP-immunoreactivities are up- regulated in CNTF- treated human corneas in organ cultures. Further, preliminary studies of the bovine cornea showed 1) the presence of CNTF receptor and VIP mRNA in the CEC, 2) VIP treatment helped the CEC in trephined cornea buttons to survive subsequent hydrogen peroxide treatment, and 3) VIP helped to preserve the hexagonal cell borders of the CEC in cornea organ cultures. Our long-term goal is to demonstrate that CNTF and VIP are trophic factors of human CEC capable of 1) prolonging the duration of preservation of corneas for transplantation and 2) maintaining the integrity. Of transplanted corneas in recipient eyes.
Our specific aims are: To test the hypothesis that 1. The CNTF-induced VIP protein expression in human CEC is mediated through CNTF induction of VIP gene expression. 2. VIP is released from human CEC and is an autocrine factor for human CEC, and that there is an effect of aging on VIP/VIP receptor expression. 3, CNTF and VIP help to maintain the viability, the barrier function, & the integrity of CEC cell-cell junction and cell-matrix attachment in stored human corneas and in human cornea organ cultures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011607-03
Application #
6329558
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Fisher, Richard S
Project Start
1998-12-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2002-11-30
Support Year
3
Fiscal Year
2001
Total Cost
$162,808
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Koh, Shay-Whey M; Coll, Timothy; Gloria, Dante et al. (2017) Corneal Endothelial Cell Integrity in Precut Human Donor Corneas Enhanced by Autocrine Vasoactive Intestinal Peptide. Cornea 36:476-483
Koh, Shay-Whey Margaret (2012) Corneal endothelial autocrine trophic factor VIP in a mechanism-based strategy to enhance human donor cornea preservation for transplantation. Exp Eye Res 95:48-53
Koh, Shay-Whey M; Gloria, Dante; Molloy, Joseph (2011) Corneal endothelial autocrine VIP enhances its integrity in stored human donor corneoscleral explant. Invest Ophthalmol Vis Sci 52:5632-40
Koh, Shay-Whey M; Cheng, Jason; Dodson, Rebecca M et al. (2009) VIP down-regulates the inflammatory potential and promotes survival of dying (neural crest-derived) corneal endothelial cells ex vivo: necrosis to apoptosis switch and up-regulation of Bcl-2 and N-cadherin. J Neurochem 109:792-806
Koh, Shay-Whey M; Celeste, Jordan; Ku, C Y Paul (2009) Functional CNTF receptor alpha subunit restored by its recombinant in corneal endothelial cells in stored human donor corneas: connexin-43 upregulation. Invest Ophthalmol Vis Sci 50:1801-7
Koh, Shay-Whey M; Chandrasekara, Krish; Abbondandolo, Cara J et al. (2008) VIP and VIP gene silencing modulation of differentiation marker N-cadherin and cell shape of corneal endothelium in human corneas ex vivo. Invest Ophthalmol Vis Sci 49:3491-8
Koh, Shay-Whey M; Guo, Yan; Bernstein, Steve L et al. (2007) Vasoactive intestinal peptide induction by ciliary neurotrophic factor in donor human corneal endothelium in situ. Neurosci Lett 423:89-94
Koh, Shay-Whey; Rutzen, Allan; Coll, Timothy et al. (2005) VIP immunoreactivity in human aqueous humor. Curr Eye Res 30:189-94
Koh, Shay-Whey M; Coll, Timothy J; Rose, Linda et al. (2004) Antiglaucoma eye drop pulses--increased interleukin-6 secretion by Tenon's capsule fibroblast cultures. J Glaucoma 13:200-9
Koh, Shay-Whey M (2002) Ciliary neurotrophic factor released by corneal endothelium surviving oxidative stress ex vivo. Invest Ophthalmol Vis Sci 43:2887-96

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