Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Does age/stress-induced mitochondrial dysfunction induce variations in RPE phenotype in AMD?

Award Number: R01EY035805
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

Group Awards By:

View Award Description

Does age/stress-induced mitochondrial dysfunction induce variations in RPE phenotype in AMD? - Project Summary Age-related macular degeneration (AMD) coincides with retinal pigment epithelium (RPE) heterogeneity. While ordered cellular heterogeneity is beneficial, pathogenic subgroups resulted from age/stress-related heterogeneity could lead to age-related diseases. Aging and cigarette smoking (CS) are the two strongest non-genetic factors associated with AMD risk. The mechanisms whereby aging and CS drive RPE heterogeneity and these focal AMD changes are unclear. RPE mitochondrial (mt) dysfunction is a well-established pathogenic factor in AMD, and both aging and CS induce mt dysfunction. We recently reported that modest mt dysfunction from impaired mitophagy can trigger reactive oxygen species (ROS) mediated retrograde mt to nuclear signaling and RPE epithelial-mesenchymal transition (EMT), which has been identified in human AMD tissue. Senescence is a specific, terminal cellular program that induces cell cycle arrest with aging, and/or metabolic and oxidative stress. Even small numbers of senescent cells can drive age-related disease. We recently reported that mice deficient of mt phosphatase PGAM5 had mt hyperfusion, which induced significant mt dysfunction associated with changes in ROS and ATP level. As a result, a subset of RPE became senescent due to dysregulated AMPK/mTOR signaling. Similarly, our pilot data show that RPE senescence and EMT can be induced by non-lethal Cigarette Smoke Condensate (CSC). These observations suggest that mt dysfunction severity from aging/CS can initiate RPE heterogeneity. Our objective is to determine how aging and smoking induced mt dysfunction severity triggers RPE heterogeneity including EMT and senescence, to link these phenotypes with RPE dysfunction and an AMD phenotype in animal models, and identify the molecular identity of RPE heterogeneity including EMT and senescence in a smoking model of AMD and human AMD samples. Our hypothesis is that RPE mt dysfunction severity from smoking and aging induces RPE heterogeneity including EMT, senescence, and cell death, which will be tested in two specific aims (SA). SA I is to determine the extent that mt dysfunction severity from aging drives RPE heterogeneity through regulating mt dynamics. SA II is to determine the extent that mt dysfunction severity from smoking, especially when combined with aging, promotes RPE heterogeneity and an AMD phenotype. By the end of proposed project, we will have experimentally linked mt dysfunction severity with RPE EMT, senescence, and cell death, and identified therapeutic targets to test for dry AMD, a long-term goal of our labs.


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 = $634,520 )
2026	2026	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Vision Research	000	3	12/12/2025	NON-COMPETING CONTINUATION	$634,520
														Subtotal = $634,520

Issue Date FY: 2025 ( Subtotal = $651,702 )
2025	2025	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Vision Research	000	2	12/16/2024	NON-COMPETING CONTINUATION	$651,702
														Subtotal = $651,702

Issue Date FY: 2024 ( Subtotal = $610,403 )
2024	2024	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Vision Research	000	1	2/21/2024	NEW	$610,403
														Subtotal = $610,403

Grand Total All Awards = $1,896,625

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Does age/stress-induced mitochondrial dysfunction induce variations in RPE phenotype in AMD?

Award Number: R01EY035805

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer