Wednesday, July 16, 2025 7/16/2025

Role of Retinal Capillary Stiffness in Diabetic Retinopathy

Award Number: R01EY028242
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2023

Group Awards By:

View Award Description

Role of Retinal Capillary Stiffness in Diabetic Retinopathy - PROJECT ABSTRACT Diabetic retinopathy (DR) is a major, potentially blinding, microvascular complication of diabetes and the leading cause of vision loss in the working-age population. Although current clinical therapies aim to resolve the advanced stages of DR, there is a recognition that more effective DR management can be achieved by tackling the disease at the early stage. Diabetes-induced retinal inflammation is strongly implicated in the pathogenesis of DR. Retinal endothelial activation (ICAM-1 expression) plays a major role in inflammation because inhibiting ICAM-1 alone blocks retinal capillary leukostasis, hyperpermeability, and degeneration associated with DR. But precisely how retinal endothelial cells (ECs) become activated in diabetes is not properly understood. Since diabetes has been strongly associated with increased stiffness of the aorta and arteries, which undergo chronic inflammation, we asked whether diabetes also leads to stiffening of retinal capillaries and, if so, whether the increased capillary stiffness promotes retinal inflammation in diabetes. Our preliminary data has revealed that retinal capillaries in diabetic mice are significantly stiffer than those in normal mice, which correlates with increased lysyl oxidase (LOX) expression. Pharmacological inhibition of LOX-dependent capillary stiffening alone blocks retinal endothelial ICAM-1 associated with diabetes. Our preliminary studies have also revealed that this stiffness-dependent control of retinal inflammation in diabetes is mediated by the mechanosensitive and proinflammatory small GTPase Rho and its downstream effector ROCK, which is markedly upregulated in retinal capillaries of diabetic mice and HG-treated retinal EC cultures. Based on these observations, we hypothesize that diabetes leads to LOX-dependent stiffening of retinal capillaries and elevated Rho/ROCK that, in turn, promotes NF-kB-mediated endothelial ICAM-1 expression and retinal inflammation associated with early DR. The objective of this proposal is to uncover the link between diabetes, retinal capillary stiffness, endothelial mechanotransduction, and retinal inflammation. To achieve this goal, we will pursue the following specific aims. Aim 1: To fully examine the effects of pharmacologic and genetic inhibition of LOX on retinal capillary stiffening-dependent inflammation and vascular lesions of early DR; Aim 2: To determine the extent to which diabetes-induced biochemical changes in the retina contribute to LOX-dependent retinal capillary stiffening; and Aim 3: To delineate the mechanotransduction mechanism underlying capillary stiffening-dependent retinal inflammation in diabetes.


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 = $0 )
2024	2021	DOHENY EYE INSTITUTE	150 N ORANGE GROVE BLVD	PASADENA	CA	91103	LOS ANGELES	USA	Vision Research	000	6	4/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $377,419 )
2021	2021	DOHENY EYE INSTITUTE	1355 SAN PABLO ST	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	003	6	6/28/2021	NON-COMPETING CONTINUATION	$377,419
2021	2019	DOHENY EYE INSTITUTE	150 N ORANGE GROVE BLVD	PASADENA	CA	91103	LOS ANGELES	USA	Vision Research	002	4	3/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$251,906
2021	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Vision Research	001	3	3/8/2021	NON-COMPETING CONTINUATION	-$146,145
2021	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Vision Research	000	2	3/8/2021	NON-COMPETING CONTINUATION	-$105,761
														Subtotal = $377,419

Issue Date FY: 2020 ( Subtotal = $389,091 )
2020	2020	DOHENY EYE INSTITUTE	1355 SAN PABLO ST	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	003	5	9/4/2020	NON-COMPETING CONTINUATION	$389,091
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Vision Research	000	3	7/8/2020	NON-COMPETING CONTINUATION	-$232,422
2020	2019	DOHENY EYE INSTITUTE	1355 SAN PABLO ST	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	002	4	8/31/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2019	DOHENY EYE INSTITUTE	1355 SAN PABLO ST	LOS ANGELES	CA	90033	LOS ANGELES	USA	Vision Research	001	4	7/8/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$232,422
														Subtotal = $389,091

Issue Date FY: 2019 ( Subtotal = $378,567 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Vision Research	000	3	6/26/2019	NON-COMPETING CONTINUATION	$378,567
														Subtotal = $378,567

Issue Date FY: 2018 ( Subtotal = $378,944 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Vision Research	000	2	6/21/2018	NON-COMPETING CONTINUATION	$378,944
														Subtotal = $378,944

Issue Date FY: 2017 ( Subtotal = $392,609 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Vision Research	000	1	8/23/2017	NEW	$392,609
														Subtotal = $392,609

Grand Total All Awards = $1,916,630

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of Retinal Capillary Stiffness in Diabetic Retinopathy

Award Number: R01EY028242

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer