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The Influence of Capsule Composition on Lens Biology

Award Number: R01EY015279
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2003
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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The Influence of Capsule Composition on Lens Biology - Extracapsular cataract surgery is a marvel of modern medicine that has greatly reduced the global burden of cataract-related blindness. However, optimal implantation of a replacement intraocular lens requires preservation of most of the lens capsule, the basement membrane surrounding the lens. Since lens epithelial cells (LECs) are tightly attached to the lens capsule, it is not possible to remove all LECs during cataract surgery, and these cells undergo robust wound healing responses characterized by cell proliferation and the transdifferentiation of LECs to scar producing myofibroblasts. While modern intraocular lens implants can sequester myofibroblasts away from the ocular axis short term, these cells can survive long term at the periphery of the capsular bag, and often escape years after surgery, migrating into the visual axis, where they can proliferate, wrinkle the capsule, and produce fibrotic extracellular matrix molecules, leading to the onset of posterior capsular opacification (PCO) years after the initial cataract surgery. Thus, understanding the mechanisms by which myofibroblasts differentiate post lens injury, and maintain their phenotype long term is of great importance. During the last grant cycle, we discovered that fibronectin produced by lens cells after surgery was critical for the maintenance of the fibrotic phenotype of LECs post fiber cell removal while RNAseq profiling revealed that numerous inhibitors of protease activity upregulate their expression dramatically in LECs following lens injury suggesting a key role for fibrotic ECM in establishing and sustaining fibrotic PCO. This proposal seeks to investigate the molecular mechanisms by which fibronectin regulates the fibrotic phenotype of lens epithelial cells and the role of matrix regulators in this process.


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: 2024 ( Subtotal = $391,376 )
2024	2024	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	20	5/20/2024	NON-COMPETING CONTINUATION	$391,376
														Subtotal = $391,376

Issue Date FY: 2023 ( Subtotal = $391,587 )
2023	2023	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	002	19	4/21/2023	NON-COMPETING CONTINUATION	$391,587
2023	2022	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	001	18	12/28/2022	COMPETING CONTINUATION	$37,750
2023	2021	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	17	12/28/2022	NON-COMPETING CONTINUATION	-$37,750
														Subtotal = $391,587

Issue Date FY: 2022 ( Subtotal = $391,792 )
2022	2022	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	18	4/15/2022	COMPETING CONTINUATION	$391,792
														Subtotal = $391,792

Issue Date FY: 2021 ( Subtotal = $370,728 )
2021	2021	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	17	4/7/2021	NON-COMPETING CONTINUATION	$370,728
														Subtotal = $370,728

Issue Date FY: 2020 ( Subtotal = $382,422 )
2020	2020	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	16	5/6/2020	NON-COMPETING CONTINUATION	$382,422
														Subtotal = $382,422

Issue Date FY: 2019 ( Subtotal = $382,643 )
2019	2019	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	15	4/8/2019	NON-COMPETING CONTINUATION	$382,643
														Subtotal = $382,643

Issue Date FY: 2018 ( Subtotal = $382,857 )
2018	2018	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	14	4/19/2018	COMPETING CONTINUATION	$382,857
2018	2017	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	001	13	9/16/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $382,857

Issue Date FY: 2017 ( Subtotal = $390,000 )
2017	2017	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	001	13	8/9/2017	NON-COMPETING CONTINUATION	$39,000
2017	2017	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	13	3/30/2017	NON-COMPETING CONTINUATION	$351,000
														Subtotal = $390,000

Issue Date FY: 2016 ( Subtotal = $390,000 )
2016	2016	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	12	3/11/2016	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2015 ( Subtotal = $382,200 )
2015	2015	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	11	3/17/2015	NON-COMPETING CONTINUATION	$382,200
														Subtotal = $382,200

Issue Date FY: 2014 ( Subtotal = $389,375 )
2014	2014	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	001	10	3/26/2014	COMPETING CONTINUATION	$389,375
2014	2012	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	9	3/20/2014	COMPETING CONTINUATION	$0
														Subtotal = $389,375

Issue Date FY: 2012 ( Subtotal = $382,500 )
2012	2012	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	001	9	9/18/2012	COMPETING CONTINUATION	$382,500
2012	2011	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	8	9/14/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $382,500

Issue Date FY: 2011 ( Subtotal = $415,506 )
2011	2011	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	8	6/14/2011	NON-COMPETING CONTINUATION	$415,506
														Subtotal = $415,506

Issue Date FY: 2010 ( Subtotal = $432,819 )
2010	2010	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	7	6/14/2010	NON-COMPETING CONTINUATION	$432,819
														Subtotal = $432,819

Issue Date FY: 2009 ( Subtotal = $437,191 )
2009	2009	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	6	6/17/2009	NON-COMPETING CONTINUATION	$437,191
														Subtotal = $437,191

Issue Date FY: 2008 ( Subtotal = $429,541 )
2008	2008	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	001	5	6/19/2008	SUPPLEMENT FOR EXPANSION	$54,691
2008	2008	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	5	5/26/2008	NON-COMPETING CONTINUATION	$374,850
														Subtotal = $429,541

Issue Date FY: 2007 ( Subtotal = $382,500 )
2007	2007	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	4	7/6/2007	COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2006 ( Subtotal = $221,177 )
2006	2006	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	3	1/19/2006	NON-COMPETING CONTINUATION	$221,177
														Subtotal = $221,177

Issue Date FY: 2005 ( Subtotal = $226,500 )
2005	2005	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	2	11/19/2004	NON-COMPETING CONTINUATION	$226,500
														Subtotal = $226,500

Issue Date FY: 2004 ( Subtotal = $226,500 )
2004	2004	UNIVERSITY OF DELAWARE	210 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Vision Research	000	1	12/1/2003	NEW	$226,500
														Subtotal = $226,500

Grand Total All Awards = $7,399,214

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The Influence of Capsule Composition on Lens Biology

Award Number: R01EY015279

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2003

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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