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IOP and Cerebrospinal Fluid Pressure-related Risk Factors for Glaucoma

Award Number: R01EY026035
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2015
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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IOP and Cerebrospinal Fluid Pressure-related Risk Factors for Glaucoma - ABSTRACT Glaucoma is a leading cause of permanent vision loss worldwide, but the mechanisms of damage are not fully understood. The retinal ganglion cells (RGC) and their axons transmit visual information from the retina to the brain, and these axons pass out of the eye through the scleral canal at the optic nerve head (ONH), which is spanned by a fenestrated connective tissue structure known as the lamina cribrosa (LC). The preponderance of evidence suggests that the RGC axons are damaged in the laminar region of the ONH in glaucoma. One of the most consistent glaucoma risk factors is elevated intraocular pressure (IOP), although the “safe” IOP threshold varies widely among individuals. While there is some evidence that IOP fluctuations contribute to glaucoma, prior studies have been hampered by the absence of continuous IOP measurement. Retrobulbar cerebrospinal fluid pressure (CSFP) surrounding the optic nerve partially counteracts IOP at the LC through the translaminar pressure (TLP=IOP-CSFP). Retrospective clinical studies have suggested that higher CSFP (and low TLP) is protective for glaucoma and low CSFP (and high TLP) increases glaucoma risk, after accounting for the effects of IOP. In addition, since the LC bears the bulk of the pressure load in the ONH due to its high stiffness relative to the surrounding neural tissues, LC thickness plays a critical role in the distribution of TLP in the ONH via the translaminar pressure gradient (TLPG = TLP/LC thickness), adding a morphological component to TLP. Hence, the goal of this project is to test the hypotheses that IOP, TLP, and TLPG fluctuations independently contribute to eye-specific susceptibility to glaucoma onset and progression after accounting for differential mean IOP in fellow eyes, and confirm the recent finding that CSFP and IOP are coupled via neural pathways. In this project, we will perform mechanical compliance testing to quantify LC deformations in vivo in response to controlled acute TLP challenge, in an animal model of unilateral glaucoma instrumented with continuous IOP, CSFP, TLP, and TLPG telemetry. We will then determine the relationships between axonal and visual function loss per unit of differential mean IOP in fellow eyes and 1) transient and diurnal IOP fluctuation, 2) TLP and TLPG (mean and fluctuation) and 3) LC deformations in response to acute TLP challenge, measured while the eye is normal and after glaucoma onset and progression. Impact: If results show that IOP fluctuations, TLP and/or TLPG contribute to glaucoma pathogenesis and progression in addition to mean IOP, new therapeutic approaches could be developed to modulate these factors to treat 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: 2025 ( Subtotal = $570,099 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	001	8	6/4/2025	NON-COMPETING CONTINUATION	$570,099
2025	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	7	1/27/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $570,099

Issue Date FY: 2024 ( Subtotal = $576,267 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	7	5/31/2024	NON-COMPETING CONTINUATION	$576,267
														Subtotal = $576,267

Issue Date FY: 2023 ( Subtotal = $579,883 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	001	6	7/3/2023	NON-COMPETING CONTINUATION	$579,883
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	5	1/17/2023	COMPETING CONTINUATION	$0
														Subtotal = $579,883

Issue Date FY: 2022 ( Subtotal = $594,328 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	5	9/2/2022	COMPETING CONTINUATION	$594,328
														Subtotal = $594,328

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	4	6/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $434,730 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	4	11/19/2018	NON-COMPETING CONTINUATION	$434,730
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	001	4	4/22/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $434,730

Issue Date FY: 2018 ( Subtotal = $483,493 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	3	12/5/2017	NON-COMPETING CONTINUATION	$427,471
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	001	3	6/4/2018	NON-COMPETING CONTINUATION	$56,022
														Subtotal = $483,493

Issue Date FY: 2017 ( Subtotal = $465,071 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	2	2/20/2017	NON-COMPETING CONTINUATION	$448,472
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	001	2	9/12/2017	NON-COMPETING CONTINUATION	$16,599
														Subtotal = $465,071

Issue Date FY: 2016 ( Subtotal = $495,311 )
2016	2016	UNIVERSITY OF ALABAMA AT BIRMINGHAM	1530 3rd Avenue South, AB 1170	BIRMINGHAM	AL	35294	JEFFERSON	USA	Vision Research	000	1	11/24/2015	NEW	$495,311
														Subtotal = $495,311

Grand Total All Awards = $4,199,182

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IOP and Cerebrospinal Fluid Pressure-related Risk Factors for Glaucoma

Award Number: R01EY026035

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2015

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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