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Proline metabolism in retinal health

Award Number: R01EY032462
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Proline metabolism in retinal health - PROJECT SUMMARY/ABSTRACT Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. A common feature in AMD is the early damage of retinal pigment epithelium (RPE), a monolayer of cells between photoreceptors and choroid. RPE controls nutrient transport from choroid blood supply to the outer retina and multiple lines of evidence show that the altered metabolism in RPE is the underlying mechanism for AMD. The long-term goal of this project is to identify key metabolic features of RPE and the roles that they play in AMD. We recently found that besides glucose, RPE preferentially uses proline, an amino acid, to fuel its metabolism. Mutations of enzymes in proline metabolism in humans could cause chorioretinal atrophy or retinal degeneration. The observation that a proline transporter is highly enriched in RPE but not in photoreceptors, further supporting our finding. The proline transporter is a novel risk gene linked to AMD. In our preliminary data, we show that knockout of the proline transporter blocks proine utilization and impairs visual function. The objective of this proposal is to study proline metabolism in RPE and its role in retinal degeneration. We plan to rigorously investigate the role of proline in healthy and diseased RPE using advanced tracer methodology, mass spectrometry, in vivo infusion, live imaging, and proline transporter knockout mouse models. The outcome of this research will be to establish a conceptual framework for RPE metabolism that describes how RPE uses nutrients to maintain metabolic homeostasis with the outer retina. This new knowledge will provide the basis for understanding the mechanisms of AMD and lay the foundation for developing new treatments.


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 = $380,000 )
2025	2025	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Vision Research	000	5	3/14/2025	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2024 ( Subtotal = $380,000 )
2024	2024	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Vision Research	000	4	4/4/2024	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2023 ( Subtotal = $380,000 )
2023	2023	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE ROAD	MORGANTOWN	WV	26505	MONONGALIA	USA	Vision Research	000	3	3/20/2023	NON-COMPETING CONTINUATION	$380,000
														Subtotal = $380,000

Issue Date FY: 2022 ( Subtotal = $368,600 )
2022	2022	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Vision Research	000	2	4/4/2022	NON-COMPETING CONTINUATION	$368,600
														Subtotal = $368,600

Issue Date FY: 2021 ( Subtotal = $380,000 )
2021	2021	WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION	886 CHESTNUT RIDGE	MORGANTOWN	WV	26506	MONONGALIA	USA	Vision Research	000	1	5/26/2021	NEW	$380,000
														Subtotal = $380,000

Grand Total All Awards = $1,888,600

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Proline metabolism in retinal health

Award Number: R01EY032462

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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