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Mechanisms and consequences of impaired glutathione homeostasis in the aging lens

Award Number: R01EY028158
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Mechanisms and consequences of impaired glutathione homeostasis in the aging lens - Abstract The integrity of the lipid and cholesterol-enriched lens membrane is vital to lens homeostasis, stiffness, and transparency, serving as an impermeable barrier to cations and scaffold for major lens membrane proteins, such as aquaporin 0 (AQP0) and ion pump. Aging is a primary risk factor for cataractogenesis and presbyopia, and it drives a significant degree of lens membrane lipids compositional changes, such as the decline of unsaturated glycerophospholipids and the steady increase of more saturated sphingomyelin lipids. The steep decline of highly unsaturated glycerophospholipids in the lens is believed to result from selective lipid peroxidation, closely associated with lens stiffness and membrane disintegration. Accumulated lens membrane disintegration can cause a cataract, and increased lens stiffness is a primary cause of presbyopia. Despite overwhelming suggestions, the direct link between lipid peroxidation and lens membrane transformation, and its impact on lens stiffness and opacity, has yet to be established. Our studies have suggested that GPX4/GSH plays a crucial role in maintaining lens plasma membrane integrity and transparency, as well as protecting against lipid peroxidation- mediated cell death, such as ferroptosis. In this application, we aim to address these questions using in vitro lens epithelial cell culture and in vivo mouse models directly targeting GPX4. The outcome of this study will provide valuable insights into the lens membrane biology of aging and age-related cataractogenesis and presbyopia.


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 = $385,000 )
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	002	7	1/13/2025	NON-COMPETING CONTINUATION	$385,000
2025	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	001	6	11/20/2024	COMPETING CONTINUATION	$70,922
2025	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	5	11/20/2024	NON-COMPETING CONTINUATION	-$70,922
														Subtotal = $385,000

Issue Date FY: 2024 ( Subtotal = $385,000 )
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	6	1/11/2024	COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2022 ( Subtotal = $373,450 )
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	5	3/21/2022	NON-COMPETING CONTINUATION	$373,450
														Subtotal = $373,450

Issue Date FY: 2021 ( Subtotal = $373,450 )
2021	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	4	4/1/2021	NON-COMPETING CONTINUATION	$373,450
														Subtotal = $373,450

Issue Date FY: 2020 ( Subtotal = $384,063 )
2020	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	3	3/18/2020	NON-COMPETING CONTINUATION	$384,063
														Subtotal = $384,063

Issue Date FY: 2019 ( Subtotal = $381,250 )
2019	2019	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	001	2	4/8/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$381,250
2019	2019	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	003	2	6/4/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$358,513
2019	2018	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Vision Research	000	1	4/8/2019	NEW	$0
2019	2018	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Vision Research	002	1	6/4/2019	NEW	-$358,513
														Subtotal = $381,250

Issue Date FY: 2018 ( Subtotal = $400,000 )
2018	2018	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Vision Research	000	1	3/26/2018	NEW	$400,000
														Subtotal = $400,000

Grand Total All Awards = $2,682,213

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Mechanisms and consequences of impaired glutathione homeostasis in the aging lens

Award Number: R01EY028158

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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