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Characterizing the role of mitochondrial DNA mutations on retinal degeneration.

Award Number: F31EY035133
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Characterizing the role of mitochondrial DNA mutations on retinal degeneration. - PROJECT SUMMARY: Retinal cell health is a vital aspect of ophthalmic biology allowing us to see the world around us every day. Degeneration of the retina and/or retinal pigment epithelium (RPE) is a central cause of numerous clinical eye disorders such as age-related macular degeneration, retinitis pigmentosa, or glaucoma. Recent investigation into disease etiology has implicated oxidative stress and mitochondrial dysfunction as key players in the initiation of an unhealthy retina. More specifically, analysis of primary tissue from human donors have shown increases in mitochondrial DNA (mtDNA) mutations in these samples. This study uses novel pre-clinical models to test the hypothesis that impaired mitochondrial function due to mtDNA damage results in age-related retinal and RPE degeneration. To address this hypothesis we are utilizing polymerase gamma (Pol γ) as a tool to study the impact of mtDNA mutation burden on retinal health in both animal and cellular models. Previously developed mutated versions of Pol γ have shown to drastically increase mtDNA mutation rate, rendering this an effective method to analyze the impact mtDNA mutations have on specific biological mechanisms. The goal of this proposal is to determine the contribution mtDNA damage has on the onset and progression of retinal degeneration. This study will pinpoint how mitochondrial dysfunction and oxidative stress driven by mtDNA mutations promote an unhealthy state of the retina. Successful completion of this study will not only offer deeper mechanistic understanding of retinal disease, but may also open a novel avenue for therapeutic targeting.


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 = $49,538 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Vision Research	000	2	1/14/2025	NON-COMPETING CONTINUATION	$48,974
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Vision Research	001	2	7/31/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $49,538

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Vision Research	000	1	11/30/2023	NEW	$47,694
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Vision Research	002	1	5/10/2024	NEW	$1,280
2024	2024	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Vision Research	001	1	11/30/2023	NEW	$0
														Subtotal = $48,974

Grand Total All Awards = $98,512

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Characterizing the role of mitochondrial DNA mutations on retinal degeneration.

Award Number: F31EY035133

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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