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ELEVATED POTASSIUM ION IN LACRIMAL FLUID AND THE HEALTH OF THE OCULAR SURFACE

Award Number: R01EY018100
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2007
PERIOD OF PERFORMANCE END DATE: 05/31/2010

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ELEVATED POTASSIUM ION IN LACRIMAL FLUID AND THE HEALTH OF THE OCULAR SURFACE - DESCRIPTION (provided by applicant): The tears differ from most extracellular fluids in that the K+ concentration of tears is about 20 mEq/l. It is thought that the ducts of the lacrimal gland secrete K+; however, the mechanism of this secretion has not been fully elucidated, and the purpose of the high [K+] in tears with respect to its relationship to the cells of the ocular surface is unknown. The key hypotheses to be addressed are based on these observations: 1) Lacrimal gland ducts express K+ transporters and channels consistent with secretion of K+ by the ducts, 2) UV radiation causes opening of K+ channels and loss of K+ from corneal epithelial cells and this loss of K+ activates apoptotic pathways. 3) Elevating extracellular K+ ([K+]o) prevents activation of apoptotic pathways in lymphocytes. We propose that the lacrimal gland duct cells secrete fluid high in K+, which provides the ocular surface with an extracellular ionic environment that protects these cells from the deleterious effects of ambient levels of ultraviolet (UV) radiation. The relatively high level of K+ in tears prevents the loss of intracellular K+ and the activation of apoptotic mechanisms when ocular surface cells are exposed to UV radiation. The specific aims of the proposed research are, 1) to determine, using patch clamp recording, whether K+ and Cl- channels, previously identified in lacrimal duct cells by microarrays and confocal microscopy are active in these cells. 2) To determine the role of elevated [K+] in tears, corneal epithelial cells will be exposed to UV radiation in the presence of varying [K+]o followed by measurement of cell viability, activation of apoptotic pathways and activity of ion channels, 3) To determine whether elevating [K+] in culture medium will promote the proliferation and viability corneal epithelial cells in culture. This study of the role of high potassium in tears will elucidate the relationship of the tears to the health of the eye in normal individuals and dry-eye patients. Everyone is exposed to ambient UV radiation and the proposed research will help to explain how the cornea protects the lens and retina from UV radiation while suffering minimal damage. In dry eye disease an inadequate tear film may make the cornea more susceptible to damage by UV radiation, thereby contributing to the disease process. If the high potassium in tears is important for the health of the ocular surface, this information will be useful in the development of improved treatments for dry eye disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2009 ( Subtotal = $197,365 )
2009	2009	CALVIN COLLEGE	3201 BURTON STREET SOUTHEAST	GRAND RAPIDS	MI	49546	KENT	USA	Vision Research	000	3	5/13/2009	NON-COMPETING CONTINUATION	$189,122
2009	2009	CALVIN COLLEGE	3201 BURTON STREET SOUTHEAST	GRAND RAPIDS	MI	49546	KENT	USA	Trans-NIH Recovery Act Research Support	001	3	6/3/2009	SUPPLEMENT FOR EXPANSION	$8,243
														Subtotal = $197,365

Issue Date FY: 2008 ( Subtotal = $184,404 )
2008	2008	CALVIN COLLEGE	3201 BURTON STREET SOUTHEAST	GRAND RAPIDS	MI	49546	KENT	USA	Vision Research	000	2	5/22/2008	NON-COMPETING CONTINUATION	$184,404
														Subtotal = $184,404

Issue Date FY: 2007 ( Subtotal = $187,237 )
2007	2007	CALVIN COLLEGE	3201 BURTON STREET SOUTHEAST	GRAND RAPIDS	MI	49546	KENT	USA	Vision Research	000	1	3/15/2007	NEW	$187,237
														Subtotal = $187,237

Grand Total All Awards = $569,006

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ELEVATED POTASSIUM ION IN LACRIMAL FLUID AND THE HEALTH OF THE OCULAR SURFACE

Award Number: R01EY018100

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2007

PERIOD OF PERFORMANCE END DATE: 05/31/2010

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