Tuesday, July 1, 2025 7/1/2025

Autophagy and Mechanotransduction in the Trabecular Meshwork

Award Number: R01EY026885
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 11/30/2025

Group Awards By:

View Award Description

Autophagy and Mechanotransduction in the Trabecular Meshwork - ABSTRACT The trabecular meshwork (TM) is a pressure sensitive tissue located in the anterior segment of the eye, key regulator of intraocular pressure. Malfunction of this tissue results in improper drainage of aqueous humor (AH) outflow, leading to ocular hypertension, the major risk factor for developing glaucoma. The TM consists of an irregular lattice of collagen beams lined by TM endothelial-like cells, followed a zone of loose connective tissue- containing TM cells, through which AH must pass before leaving the eye. Changes in pressure gradients and fluid flow associated with eye movement, circadian rhythm or the ocular pulse cause small and high variations in intraocular pressure (IOP), which are translated in continuous cycles of tissue deformation and relaxation. Cells in the TM are known to be able of sensing these deformations as mechanical forces and respond to them by eliciting a variety of different responses. Our laboratory has identified activation of autophagy and the nuclear translocation of the autophagy marker LC3, in TM cells following application of mechanical stretch. Activation of autophagy was also observed in TM cells quickly after pressure elevation in porcine perfused eyes and in ocular hypertensive mouse models. This prompted us to propose autophagy as a crucial physiological response triggered in TM cells in response to strain to adapt to mechanical forces and maintain cellular homeostasis, which exerts a dual role in repair and mechanotransduction. The nature of the mechanosensor, mechanosignaling, and exact roles of autophagy in TM cell and tissue function are still not characterized. The goal of this application is to investigate an interplay between autophagy, primary cilium and mechanotransduction in TM cells and to determine the role of such interplay in outflow pathway physiology and pathophysiology. More in particular, we will test the hypothesis that autophagy plays a critical role in TM mechanotransduction by maintaining primary cilia prevalence and length, and that dysregulation of autophagy with aging and in the glaucomatous outflow pathway compromises primary cilia-dependent IOP homeostatic response. We anticipate that completion of this project will contribute to a further understanding of the role of autophagy in outflow pathway tissue physiology and pathophysiology. Most relevant, our studies have the potential of identifying a novel therapeutic target for the treatment of ocular hypertension and glaucoma.


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 = $450,475 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Vision Research	000	9	11/27/2024	NON-COMPETING CONTINUATION	$450,475
														Subtotal = $450,475

Issue Date FY: 2024 ( Subtotal = $453,249 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Vision Research	000	8	11/29/2023	NON-COMPETING CONTINUATION	$453,249
														Subtotal = $453,249

Issue Date FY: 2023 ( Subtotal = $453,249 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Vision Research	000	7	12/1/2022	NON-COMPETING CONTINUATION	$407,924
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Vision Research	001	7	3/8/2023	NON-COMPETING CONTINUATION	$45,325
														Subtotal = $453,249

Issue Date FY: 2022 ( Subtotal = $448,419 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Vision Research	003	6	8/30/2022	COMPETING CONTINUATION	$1
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	001	6	2/11/2022	COMPETING CONTINUATION	$448,419
2022	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	000	5	2/7/2022	NON-COMPETING CONTINUATION	$0
2022	2020	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Vision Research	002	5	8/30/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $448,419

Issue Date FY: 2020 ( Subtotal = $438,522 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	000	5	7/27/2020	NON-COMPETING CONTINUATION	$438,522
														Subtotal = $438,522

Issue Date FY: 2019 ( Subtotal = $438,522 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	001	4	7/17/2019	NON-COMPETING CONTINUATION	$438,522
2019	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	000	3	4/11/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $438,522

Issue Date FY: 2018 ( Subtotal = $438,522 )
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	000	3	8/6/2018	NON-COMPETING CONTINUATION	$438,522
														Subtotal = $438,522

Issue Date FY: 2017 ( Subtotal = $438,522 )
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Vision Research	000	2	7/24/2017	NON-COMPETING CONTINUATION	$438,522
														Subtotal = $438,522

Issue Date FY: 2016 ( Subtotal = $438,522 )
2016	2016	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Vision Research	000	1	8/25/2016	NEW	$438,522
														Subtotal = $438,522

Grand Total All Awards = $3,998,002

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Autophagy and Mechanotransduction in the Trabecular Meshwork

Award Number: R01EY026885

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 11/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer