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IOP-Related Force and Failure in the Optic Nerve Head

Award Number: R01EY011610
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1998
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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IOP-Related Force and Failure in the Optic Nerve Head - Project Summary/Abstract In the previous project period we completed our 3D histomorphometric characterization of connective tissue deformation and remodeling in early through end-stage monkey experimental glaucoma (EG). Based on those findings, in this renewal proposal we will seek to identify important molecular and cellular components of optic nerve head (ONH) connective tissue and retrolaminar myelin remodeling in monkey early experimental glaucoma (EG). In so doing we will identify age-related differences in these phenomena and provide unprecedented microscopic support for their early in vivo detection by optical coherence tomography (OCT). In Aim 1 we will phenotype the ONHs of young and old monkeys with unilateral early EG using quantitative proteomic, immunohistochemistry (IHC), in situ hybridization (ISH) and electron microscopy (EM) techniques. We hypothesize that connective tissue and retrolaminar myelin remodeling are core components of ONH aging and glaucoma and will test predictions regarding their timing, and character in monkey early EG relative to the development of retinal ganglion cell (RGC) cytoarchitecture disruption, alterations in the ONH constituent cells, and the presence of wound healing, inflammation and monocyte/macrophage infiltration. In Aim 2 we will explore our hypothesis that the pathophysiology of ONH aging overlaps with glaucoma by testing two predictions regarding old vs young Control eye differences in the Aim 1 data: first that they will share important features of EG vs Control eye differences in monkeys of all ages; and second that they will also share important features of old vs young EG eye differences in monkey early EG. In Aim 3 we will accurately colocalize Aim 1 IHC/ISH/EM findings to sacrifice-day OCT B-scans of the same eyes so as to provide light and electron microscopic validation in monkeys for ONH OCT detection of early glaucoma damage in humans. To accomplish these aims we will employ: state of the art quantitative iTRAQ Mass Spectroscopy; our novel strategy for quantitative ONH IHC/ISH; quantitative transmission and scanning block face EM; precise anatomic colocalization of each IHC/ISH paraffin and each EM vibratome section to OCT B-scans, retrolaminar optic nerve (ON) axon counts, and sacrifice day OCT change-from-baseline data. All outcomes will be reported in anatomically consistent, 30º degree ONH sectors that are oriented relative to the foveal-BMO axis. Aim 1 will generate the first quantitative proteomic characterization of the monkey ONH, peripapillary scleral (pp-scleral), ON and retinal tissues in early EG. IHC/ISH and EM studies will demonstrate that connective tissue and myelin remodeling are present at an early stage of RGC axonal insult. They will also detect alterations in the ONH and pp-scleral tissues and cells that include proliferation, phagocytosis, myofibroblast differentiation, wound healing, monocyte infiltration, and inflammation. Aim 2 will confirm that proteomic, IHC protein expression and EM differences in old versus young control eyes share important features with early EG vs control eye differences in monkeys of all ages. Aim 3 will provide the first rigorous microscopic validation of deep ONH visualization and early glaucoma ONH change detection by OCT.


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: 2022 ( Subtotal = $0 )
2022	2020	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	23	7/22/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $590,809 )
2020	2020	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	23	4/16/2020	NON-COMPETING CONTINUATION	$590,809
														Subtotal = $590,809

Issue Date FY: 2019 ( Subtotal = $579,552 )
2019	2019	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	22	3/4/2019	NON-COMPETING CONTINUATION	$579,552
														Subtotal = $579,552

Issue Date FY: 2018 ( Subtotal = $584,166 )
2018	2018	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	21	3/12/2018	NON-COMPETING CONTINUATION	$525,750
2018	2018	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	001	21	7/12/2018	NON-COMPETING CONTINUATION	$58,416
														Subtotal = $584,166

Issue Date FY: 2017 ( Subtotal = $602,294 )
2017	2017	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	003	20	7/24/2017	COMPETING CONTINUATION	$46,488
2017	2017	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	001	20	2/13/2017	COMPETING CONTINUATION	$602,294
2017	2015	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	19	2/8/2017	NON-COMPETING CONTINUATION	$0
2017	2015	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	002	19	7/24/2017	NON-COMPETING CONTINUATION	-$46,488
														Subtotal = $602,294

Issue Date FY: 2015 ( Subtotal = $834,663 )
2015	2015	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	19	6/15/2015	NON-COMPETING CONTINUATION	$834,663
														Subtotal = $834,663

Issue Date FY: 2014 ( Subtotal = $740,555 )
2014	2014	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	18	6/23/2014	NON-COMPETING CONTINUATION	$740,555
														Subtotal = $740,555

Issue Date FY: 2013 ( Subtotal = $733,358 )
2013	2013	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	17	7/22/2013	NON-COMPETING CONTINUATION	$733,358
														Subtotal = $733,358

Issue Date FY: 2012 ( Subtotal = $783,403 )
2012	2012	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	16	7/16/2012	COMPETING CONTINUATION	$783,403
														Subtotal = $783,403

Issue Date FY: 2011 ( Subtotal = $644,366 )
2011	2011	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	15	6/30/2011	NON-COMPETING CONTINUATION	$644,366
														Subtotal = $644,366

Issue Date FY: 2010 ( Subtotal = $687,399 )
2010	2010	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	14	6/30/2010	NON-COMPETING CONTINUATION	$687,399
														Subtotal = $687,399

Issue Date FY: 2009 ( Subtotal = $698,556 )
2009	2009	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	13	6/25/2009	NON-COMPETING CONTINUATION	$698,556
														Subtotal = $698,556

Issue Date FY: 2008 ( Subtotal = $690,916 )
2008	2008	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	12	7/14/2008	NON-COMPETING CONTINUATION	$690,916
														Subtotal = $690,916

Issue Date FY: 2007 ( Subtotal = $707,574 )
2007	2007	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	11	9/10/2007	COMPETING CONTINUATION	$707,574
														Subtotal = $707,574

Issue Date FY: 2006 ( Subtotal = $698,338 )
2006	2006	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	10	7/28/2006	NON-COMPETING CONTINUATION	$547,818
2006	2006	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	001	9	5/26/2006	SUPPLEMENT FOR EXPANSION	$150,520
														Subtotal = $698,338

Issue Date FY: 2005 ( Subtotal = $525,376 )
2005	2005	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	8	6/27/2005	NON-COMPETING CONTINUATION	$525,376
														Subtotal = $525,376

Issue Date FY: 2004 ( Subtotal = $630,242 )
2004	2004	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	7	6/23/2004	NON-COMPETING CONTINUATION	$630,242
														Subtotal = $630,242

Issue Date FY: 2003 ( Subtotal = $637,643 )
2003	2003	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	6	7/11/2003	NON-COMPETING CONTINUATION	$637,643
														Subtotal = $637,643

Issue Date FY: 2002 ( Subtotal = $616,605 )
2002	2002	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	5	9/20/2002	COMPETING CONTINUATION	$616,605
														Subtotal = $616,605

Issue Date FY: 2001 ( Subtotal = $328,054 )
2001	2001	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	4	7/13/2001	NON-COMPETING CONTINUATION	$328,054
														Subtotal = $328,054

Issue Date FY: 2000 ( Subtotal = $274,018 )
2000	2000	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	3	7/17/2000	NON-COMPETING CONTINUATION	$274,018
														Subtotal = $274,018

Issue Date FY: 1999 ( Subtotal = $298,289 )
1999	1999	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Vision Research	000	2	6/25/1999	NON-COMPETING CONTINUATION	$298,289
														Subtotal = $298,289

Issue Date FY: 1998 ( Subtotal = $234,359 ) (Continued on the next page)
Grand Total All Awards = $13,120,535

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IOP-Related Force and Failure in the Optic Nerve Head

Award Number: R01EY011610

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/1998

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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