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GENE REGULATION IN LENS REGENERATION

Award Number: R01EY010540
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/1995
PERIOD OF PERFORMANCE END DATE: 07/31/2014

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GENE REGULATION IN LENS REGENERATION - Summary/Abstract Lens regeneration is a remarkable phenomenon, which, among vertebrates and during adulthood, occurs only in some urodele amphibians. Upon lentectomy, the pigmented epithelial cells (PECs) from the dorsal iris dedifferentiate and subsequently differentiate into lens cells. While cultured PECs from the ventral iris of the newt or from irises from other animals, including humans, can transdifferentiate to lens, in vivo and especially during adulthood, this ability is restricted to the dorsal iris PECs of a few urodeles only. It has been reasoned, therefore, that these urodeles might hold the key to understanding the mechanisms involved in transdifferentiation with possible applications in other species, especially in humans. We hypothesized previously, (and that hypothesis was the core of our initial proposal), that there must be unique regulatory events in the dorsal iris upon lentectomy. If we could then coax the ventral iris to such regulation we might be able to induce regeneration from the incompetent ventral iris. Our attempts to induce lens regeneration from the ventral iris were eventually successful. Having made such a crucial step, we then performed extensive studies on gene regulation in the ventral and dorsal iris. We have identified very interesting and surprising regulation. In particular, regulatory genes that seemingly are involved in lens regeneration are expressed in both dorsal and ventral irises. Therefore, it seems that both irises initiate the events of regeneration, but somehow there must be a repressive event in the ventral iris. To address this issue we turned our attention to global genomic signatures. We have evidence of two culprits of large-scale regulation. One is differential expression of microRNAs (each one of them is known to regulate hundreds of mRNAs) and the other is specific gene repression-associated histone modifications. Furthermore, our EST and detailed gene expression analysis have revealed that several stem cell-maintaining factors are normally expressed in PECs. This might indicate a relationship of transdifferentiation to stemness and could provided unprecedented insights about the mechanisms of regeneration. To approach these issues we propose to: 1) Analyze the function of miRNAs, which are specifically regulated in the dorsal and ventral iris; 2) Analyze the role of histone modifications and the involved enzymes in relation to the process of lens regeneration and 3) correlate the expression of stem cell-maintaining factors to the mechanisms and ability of lens regeneration.


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: 2013 ( Subtotal = $323,796 )
2013	2013	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	17	7/18/2013	NON-COMPETING CONTINUATION	$323,796
														Subtotal = $323,796

Issue Date FY: 2012 ( Subtotal = $341,127 )
2012	2012	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	16	8/9/2012	NON-COMPETING CONTINUATION	$341,127
														Subtotal = $341,127

Issue Date FY: 2011 ( Subtotal = $341,402 )
2011	2011	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	15	7/18/2011	NON-COMPETING CONTINUATION	$341,402
														Subtotal = $341,402

Issue Date FY: 2010 ( Subtotal = $355,899 )
2010	2010	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	14	7/13/2010	NON-COMPETING CONTINUATION	$355,899
														Subtotal = $355,899

Issue Date FY: 2009 ( Subtotal = $350,556 )
2009	2009	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	002	13	7/29/2009	COMPETING CONTINUATION	$350,556
2009	2008	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	12	7/2/2009	NON-COMPETING CONTINUATION	$0
2009	2008	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	001	12	7/29/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $350,556

Issue Date FY: 2008 ( Subtotal = $213,228 )
2008	2008	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	12	4/21/2008	NON-COMPETING CONTINUATION	$213,228
														Subtotal = $213,228

Issue Date FY: 2007 ( Subtotal = $217,579 )
2007	2007	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	11	5/3/2007	NON-COMPETING CONTINUATION	$217,579
														Subtotal = $217,579

Issue Date FY: 2006 ( Subtotal = $214,020 )
2006	2006	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	10	5/4/2006	NON-COMPETING CONTINUATION	$214,020
														Subtotal = $214,020

Issue Date FY: 2005 ( Subtotal = $219,404 )
2005	2005	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	9	4/20/2005	NON-COMPETING CONTINUATION	$219,404
														Subtotal = $219,404

Issue Date FY: 2004 ( Subtotal = $204,812 )
2004	2004	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	8	4/19/2004	COMPETING CONTINUATION	$204,812
														Subtotal = $204,812

Issue Date FY: 2002 ( Subtotal = $167,231 )
2002	2002	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	7	5/14/2002	NON-COMPETING CONTINUATION	$167,231
														Subtotal = $167,231

Issue Date FY: 2001 ( Subtotal = $164,362 )
2001	2001	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	6	4/19/2001	NON-COMPETING CONTINUATION	$164,362
														Subtotal = $164,362

Issue Date FY: 2000 ( Subtotal = $159,634 )
2000	2000	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	5	4/24/2000	NON-COMPETING CONTINUATION	$159,634
														Subtotal = $159,634

Issue Date FY: 1999 ( Subtotal = $173,060 )
1999	1999	UNIVERSITY OF DAYTON	300 COLLEGE PARK	DAYTON	OH	45409	MONTGOMERY	USA	Vision Research	000	4	4/15/1999	COMPETING CONTINUATION	$173,060
														Subtotal = $173,060

Grand Total All Awards = $3,446,110

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GENE REGULATION IN LENS REGENERATION

Award Number: R01EY010540

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/1995

PERIOD OF PERFORMANCE END DATE: 07/31/2014

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