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TRP Channels as Master Controllers of Lens Function

Award Number: R01EY009532
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

To function normally, all cells must maintain ion homeostasis and regulate water content. The lens is unusual because it is made from a packed mass of fiber cells that are incapable of independently maintaining ion and water homeostasis. The fiber cells rely on ion transport mechanisms in a monolayer of epithelial cells at the lens surface. Na,K- ATPase and NKCC1 activity are particularly important. To monitor and control this arrangement, the lens has come to rely on exquisitely specialized remote control mechanisms that utilize TRPV4 and TRPV1 channels. A TRPV4 feedback loop senses swelling in the fiber mass and increases Na,K-ATPase activity to compensate. A TRPV1 feedback loop senses shrinkage in the fiber mass and increases NKCC1 activity to compensate. The feedback loops are important. They explain homeostatic regulation of lens ion transport as well as intracellular hydrostatic pressure, and they fit with the Mathias model of lens circulation. TRPV4 and TRPV1 appear to be master controllers of lens homeostasis. The specific aims are: (1) Test the hypothesis that the TRPV4/hemichannel/Na,K-ATPase response to swelling stretch involves a functional link between TRPV4 and the actin cytoskeleton; (2) Test the hypothesis that the TRPV1/ERK/NKCC1 response to shrinkage involves a functional link between TRPV1 and the tubulin cytoskeleton; (3) Explore reserve mechanisms of lens ion and water homeostasis. Aims 1 and 2 focus on unanswered mechanistic questions regarding TRPV4 and TRPV1 activation by opposing mechanical stimuli, TRPV4-dependent hemichannel opening, and the mechanism of NKCC1 activation. Aim 3 follows up pilot studies on reserve mechanisms that support slower homeostatic responses or serve as a fail-safe backup. The proposed studies are highly significant as regards human vision because preservation of lens transparency and refractive index gradient depends on ion and water homeostasis.


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: 2023 ( Subtotal = $402,736 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Vision Research	000	30	7/10/2023	NON-COMPETING CONTINUATION	$402,736
														Subtotal = $402,736

Issue Date FY: 2022 ( Subtotal = $390,653 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	002	29	8/4/2022	NON-COMPETING CONTINUATION	$390,653
2022	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	001	28	12/27/2021	COMPETING CONTINUATION	$0
2022	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	000	27	12/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $390,653

Issue Date FY: 2021 ( Subtotal = $416,111 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	000	28	8/17/2021	COMPETING CONTINUATION	$416,111
														Subtotal = $416,111

Issue Date FY: 2019 ( Subtotal = $447,247 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	000	27	9/11/2019	NON-COMPETING CONTINUATION	$447,247
														Subtotal = $447,247

Issue Date FY: 2018 ( Subtotal = $447,247 )
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	000	26	7/13/2018	NON-COMPETING CONTINUATION	$447,247
														Subtotal = $447,247

Issue Date FY: 2017 ( Subtotal = $447,246 )
2017	2017	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	001	25	7/24/2017	NON-COMPETING CONTINUATION	$447,247
2017	2015	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Vision Research	000	23	1/22/2017	NON-COMPETING CONTINUATION	-$1
														Subtotal = $447,246

Issue Date FY: 2016 ( Subtotal = $460,622 )
2016	2016	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	001	24	7/20/2016	COMPETING CONTINUATION	$460,622
2016	2015	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	23	7/15/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $460,622

Issue Date FY: 2015 ( Subtotal = $371,175 )
2015	2015	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	23	2/27/2015	NON-COMPETING CONTINUATION	$371,175
														Subtotal = $371,175

Issue Date FY: 2014 ( Subtotal = $371,175 )
2014	2014	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	22	2/26/2014	NON-COMPETING CONTINUATION	$371,175
														Subtotal = $371,175

Issue Date FY: 2013 ( Subtotal = $378,750 )
2013	2013	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	001	21	2/25/2013	COMPETING CONTINUATION	$378,750
2013	2012	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	20	2/25/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $378,750

Issue Date FY: 2012 ( Subtotal = $322,898 )
2012	2012	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	20	3/2/2012	NON-COMPETING CONTINUATION	$322,898
														Subtotal = $322,898

Issue Date FY: 2011 ( Subtotal = $322,898 )
2011	2011	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	19	2/3/2011	NON-COMPETING CONTINUATION	$302,717
2011	2011	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	001	19	5/26/2011	NON-COMPETING CONTINUATION	$20,181
														Subtotal = $322,898

Issue Date FY: 2010 ( Subtotal = $336,353 )
2010	2010	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	18	3/16/2010	NON-COMPETING CONTINUATION	$336,353
														Subtotal = $336,353

Issue Date FY: 2009 ( Subtotal = $339,750 )
2009	2009	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	001	17	4/27/2009	NON-COMPETING CONTINUATION	$33,975
2009	2009	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	17	2/3/2009	NON-COMPETING CONTINUATION	$305,775
														Subtotal = $339,750

Issue Date FY: 2008 ( Subtotal = $339,750 )
2008	2008	UNIVERSITY OF ARIZONA	POST OFFICE BOX 3308	TUCSON	AZ	85722	PIMA	USA	Vision Research	000	16	4/1/2008	COMPETING CONTINUATION	$339,750
														Subtotal = $339,750

Issue Date FY: 2006 ( Subtotal = $244,370 )
2006	2006	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Vision Research	000	14	6/21/2006	NON-COMPETING CONTINUATION	$244,370
														Subtotal = $244,370

Issue Date FY: 2005 ( Subtotal = $250,250 )
2005	2005	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Vision Research	000	13	7/1/2005	NON-COMPETING CONTINUATION	$250,250
														Subtotal = $250,250

Issue Date FY: 2004 ( Subtotal = $250,250 )
2004	2004	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Vision Research	000	12	6/23/2004	NON-COMPETING CONTINUATION	$250,250
														Subtotal = $250,250

Issue Date FY: 2003 ( Subtotal = $250,250 )
2003	2003	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Vision Research	000	11	7/15/2003	NON-COMPETING CONTINUATION	$250,250
														Subtotal = $250,250

Issue Date FY: 2002 ( Subtotal = $250,250 )
2002	2002	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Vision Research	000	10	6/13/2002	COMPETING CONTINUATION	$250,250
														Subtotal = $250,250

Issue Date FY: 2001 ( Subtotal = $265,002 )
2001	2001	UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION	SERVICE COMPLEX	LOUISVILLE	KY	40292	JEFFERSON	USA	Vision Research	000	9	6/29/2001	NON-COMPETING CONTINUATION	$265,002
														Subtotal = $265,002

Issue Date FY: 2000 ( Subtotal = $257,283 ) (Continued on the next page)
Grand Total All Awards = $8,054,566

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TRP Channels as Master Controllers of Lens Function

Award Number: R01EY009532

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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