Thursday, July 17, 2025 7/17/2025

The role of retinal astrocytes in dynamic blood flow autoregulation

Award Number: R01EY019939
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2010
PERIOD OF PERFORMANCE END DATE: 01/31/2021

Group Awards By:

View Award Description

The role of retinal astrocytes in dynamic blood flow autoregulation - Project Summary The long-term goal of this project is to define the cellular and molecular mechanisms underlying hemodynamic abnormalities in glaucoma and to find a means to mitigate retinal ganglion cell damage. In this project, we will test a novel hypothesis that astrocytes are central to pressure-initiated ocular BF autoregulation, as they sense transmural pressure and tissue oxygen levels to coordinate the perivascular astrocytic network and feedback to vessels to modulate diameter and thus blood flow and that failure of this mechanism results in hemodynamic imbalance. The hypothesis will be tested in rat retina and monkey optic nerve head in three specific aims: (1) Pressure-initiated retinal astrocyte activation is independent of neuronal and metabolic activity. This will be achieved by elimination of retinal ganglion cell and application of systemic hyperoxia. (2) Astrocytes modulate retinal vascular tone and coordinate pressure-initiated autoregulation under modulation by tissue oxygen status. To test the hypothesis, all or a specific pathway of the proposed feedback mechanism in the astrocytes will be inhibited and tested under hyperoxia and normoxia to compare the hemodynamic parameter changes under the conditions. (3) Pharmacological interruption of astrocyte feedback mechanism impairs hemodynamic balance within the optic nerve head and this is further modified by the alteration of oxygen supply. The following techniques are used: (1) an ex vivo system that enables precise control of intravascular and extravascular pressures thus allowing simultaneous quantifying astrocytic Ca2+ (Fluo-4AM) and changes in vascular diameter. (2) In vivo imaging of astrocytic Ca2+ (Fluo-4AM, fluorescence) and vessel diameter (infrared) using a confocal scanning laser ophthalmoscope, while blood pressure and intraocular pressure are manipulated in both rats and nonhuman primates. (3) Combining pharmacological inhibitors and adeno-associated virus 8 vector delivery with an astrocyte-specific promotor inhibit either all the bioactivity of astrocytes or the key proteins in the proposed astrocytic feedback and propagation pathways. (4) In vivo assessment of BF autoregulation in retina and optic nerve by dynamic autoregulation analysis using laser speckle imaging techniques. The proposal is expected to elucidate a novel role for astrocytes in pressure-initiated BF autoregulation, thus significantly expanding our understanding of hemodynamic control in the central nervous system. This basic understanding provides a platform for future studies of novel therapeutic targets in diseases associated with autoregulation dysfunction, including glaucoma.


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	2019	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	8	9/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = -$1,735 )
2021	2019	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	8	5/29/2021	NON-COMPETING CONTINUATION	-$1,735
														Subtotal = -$1,735

Issue Date FY: 2019 ( Subtotal = $412,500 )
2019	2019	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	8	3/11/2019	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2018 ( Subtotal = $412,500 )
2018	2018	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	7	4/9/2018	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2017 ( Subtotal = $412,500 )
2017	2017	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 N GANTENBEIN AVE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	6	3/9/2017	COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2014 ( Subtotal = $359,856 )
2014	2014	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	5	6/23/2014	NON-COMPETING CONTINUATION	$359,856
														Subtotal = $359,856

Issue Date FY: 2013 ( Subtotal = $348,840 )
2013	2013	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	4	6/12/2013	NON-COMPETING CONTINUATION	$348,840
														Subtotal = $348,840

Issue Date FY: 2012 ( Subtotal = $367,200 )
2012	2012	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	3	6/28/2012	NON-COMPETING CONTINUATION	$367,200
														Subtotal = $367,200

Issue Date FY: 2011 ( Subtotal = $367,200 )
2011	2011	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	2	6/30/2011	NON-COMPETING CONTINUATION	$367,200
														Subtotal = $367,200

Issue Date FY: 2010 ( Subtotal = $382,500 )
2010	2010	LEGACY EMANUEL HOSPITAL & HEALTH CENTER	2801 NORTH GANTENBEIN AVENUE	PORTLAND	OR	97227	MULTNOMAH	USA	Vision Research	000	1	7/15/2010	NEW	$382,500
														Subtotal = $382,500

Grand Total All Awards = $3,061,361

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of retinal astrocytes in dynamic blood flow autoregulation

Award Number: R01EY019939

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2010

PERIOD OF PERFORMANCE END DATE: 01/31/2021

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer