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Metabolism during the Progression of Photoreceptor Degeneration

Award Number: K99EY034881
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Metabolism during the Progression of Photoreceptor Degeneration - Project Summary/Abstract Retinitis pigmentosa (RP) is an inherited, early-onset, and irreversible form of vision loss. RP can result from mutations in over 100 unique genes. The burden of developing individualized treatments for each mutation is high, so strategies that improve photoreceptor health regardless of mutation would be benefit patients. RP perturbs retina energy metabolism, and disrupted energy metabolism can cause degeneration. Metabolic reprogramming may prevent photoreceptor loss. Reprogramming efforts should be aimed at correcting changes that occur with RP, yet it is unclear which changes to correct. In RP there are disruptions in glucose transport, aerobic glycolysis and the normal expression of TCA cycle and pentose phosphate pathway (PPP) genes. Due to critical gaps in these studies, the nature and timing of these changes is unclear. The lack of comprehensive detail on how RP alters metabolic flux hampers efforts to protect photoreceptors. The aims of this application are aimed at understanding changes to metabolism in RP. Specifically, in aim 1 I will determine how the rate of metabolism changes with disease stage. I will infuse 13C-labeled glucose or lactate through catheters to probe flux of carbons through metabolic pathways in the retina and RPE-choroid. I will quantify 13C accumulation in metabolites of glycolysis, the TCA cycle, the PPP, gluconeogenesis, and glycogen. Metabolites that fuel these pathways must first be transported from circulation, through the retinal pigment epithelium (RPE), and to the retina. In Aim 2 I will determine metabolites that increase O2 consumption by ex vivo RPE-choroid, and which of these best labels intermediates in the RPE-choroid in vivo. This proposal also seeks support for my career development. My development goals include presenting my work at conferences and leveraging these presentations to form a scientific network. I will also take scientific and non-scientific courses to improve my ability to perform surgeries and mentor young scientists. These opportunities will prepare me for a position as an independent investigator, where I can continue to fulfill the aims of this proposal and further develop my research program.


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: 2026 ( Subtotal = $0 )
2026	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Vision Research	000	2	1/27/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $111,742 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Vision Research	000	2	5/7/2024	NON-COMPETING CONTINUATION	$111,742
														Subtotal = $111,742

Issue Date FY: 2023 ( Subtotal = $110,708 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Vision Research	000	1	5/26/2023	NEW	$110,708
														Subtotal = $110,708

Grand Total All Awards = $222,450

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Metabolism during the Progression of Photoreceptor Degeneration

Award Number: K99EY034881

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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