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Mechanistic Insights and Therapeutic Potential of the Glutaredoxin (Grx) System in the Lens

Award Number: R21EY033941
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Mechanistic Insights and Therapeutic Potential of the Glutaredoxin (Grx) System in the Lens - Summary The most common cause of vision loss among the elderly is cataract. Oxidative stress is well known to cause cellular and tissue damage, resulting in age-associated ocular diseases, including cataract. Protein glutathionylation, the reversible formation of a mixed-disulfide between glutathione and protein thiols, is one of the major oxidative protein modifications in response to oxidative stress. The glutaredoxin (Grx) system repairs protein thiols and maintains cellular redox balance. The Grx system has two isoforms, the cytosolic Grx1 (also known as thioltransferase) and the mitochondrial Grx2. The purpose of this proposal is to study how Grx system dysfunction may affect the lens redox signaling and its transparency. We hypothesize that Grx1/Grx2 double deletion may increase the lens susceptibility to ultraviolet (UV) radiation and aging by inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant response. We also propose that Grx- activating compounds could protect the lens from UV-induced cataract formation. To prove our hypotheses, the following Specific Aims are proposed: 1) To identify the role of the Grx system in protecting the lens from UV radiation and aging using the Grx1/Grx2 DKO mouse as a model. 2) To examine the crosstalk between the Grx system and the Nrf2-antioxidant pathway. 3) To test if Grx activating compounds could protect the lens from UV-induced cataract formation. Successful completion of these aims will introduce the Grx system as a drug target and may lead to the development of Grx-activating compounds as a potential therapeutic for cataract and other oxidative stress-associated eye diseases.


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: 2024 ( Subtotal = $180,348 )
2024	2024	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Vision Research	000	2	1/29/2024	NON-COMPETING CONTINUATION	$180,348
														Subtotal = $180,348

Issue Date FY: 2023 ( Subtotal = $228,374 )
2023	2023	UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH	3500 CAMP BOWIE BLVD	FORT WORTH	TX	76107	TARRANT	USA	Vision Research	000	1	1/23/2023	NEW	$228,374
														Subtotal = $228,374

Grand Total All Awards = $408,722

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Mechanistic Insights and Therapeutic Potential of the Glutaredoxin (Grx) System in the Lens

Award Number: R21EY033941

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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