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Development and application of a high-fidelity computational model of diabetic retinopathy hemodynamics: Coupling single-cell biophysics with retinal vascular network topology and complexity

Award Number: R01EY033003
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Pathogenesis of diabetic retinopathy is characterized by the appearance of morphological abnormalities in the retinal capillary vessels. Although such abnormalities are used in the clinical evaluation of the disease severity, the hemodynamic mechanisms underlying their development and progression remain unknown. These morphological abnormalities are highly localized in specific regions of the retinal vascular network, and may correlate with the local variations of the hemodynamic parameters and forces. Diabetic conditions significantly alter the biophysical properties of the blood cells, however the influence of such altered biophysical properties on the retinal hemodynamics and pathogenesis of retinopathy are not known. Existing in vivo imaging techniques have limitations in terms of the hemodynamic measurements in the topologically complex and multi- plexus retinal vasculature. Additionally, tissue hypoxia and the loss of blood flow autoregulation are pathogenic factors in retinopathy. No study exists that correlates diabetes-mediated altered biophysics of the individual blood cell to the loss of retinal tissue oxygenation and flow regulation. Our underlying hypotheses are: (i) altered biophysics of diabetic red blood cells (RBC) alone can mediate vascular abnormalities by altering the hemodynamic parameters and forces; and (ii) such changes are spatially heterogeneous across the retinal vascular network, and correlate with the focal and heterogeneous nature of vascular abnormalities. The broad objective of this project is to understand the relationship between the hemodynamics of diabetic blood cells, retinal vascular network topology, and pathogenesis of retinopathy, using a high-fidelity, predictive computational modeling study. Specific aims are: 1) To develop a multiscale computational model of the diabetic retinopathy hemodynamics taking into consideration the precise microstructural and geometric details of the 3D vascular networks as obtained from in vivo images of the human retina, and 3D deformation of every single blood cell with altered biophysical properties representing diabetic conditions. 2) To predict diabetic RBC-mediated alteration in the retinal hemodynamics, and how such changes are correlated to the formation and heterogeneity of microvascular abnormalities and vascular adaptation at different stages of progressive retinopathy. 3) To evaluate the significance of diverse cellular-scale hemodynamic pathways involved. 4) To predict the role of RBC hemodynamics on retinal hypoxia and loss of nitric oxide bioavailability as pathogenic factors in retinopathy. This study is significant and innovative because it will (i) develop the first high-fidelity, predictive computational model that combines the exact 3D geometry of ultra-large-scale and multi-plexus in silico retinal vasculature, and 3D deformation and rheology of every blood cell, (ii) provide a rheology- topology coupling mechanism as a basis of hemodynamics-mediated initiation and progression of vascular abnormalities, (ii) directly model heterotypic individual cell-cell and cell-endothelium interactions, and (iv) couple individual RBC transient deformation with blood and retinal tissue gas transport.


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: 2023 ( Subtotal = $337,450 )
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Vision Research	000	3	7/13/2023	NON-COMPETING CONTINUATION	$337,450
														Subtotal = $337,450

Issue Date FY: 2022 ( Subtotal = $316,825 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Vision Research	000	2	8/31/2022	NON-COMPETING CONTINUATION	$316,825
														Subtotal = $316,825

Issue Date FY: 2021 ( Subtotal = $351,316 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Vision Research	000	1	8/20/2021	NEW	$351,316
														Subtotal = $351,316

Grand Total All Awards = $1,005,591

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Development and application of a high-fidelity computational model of diabetic retinopathy hemodynamics: Coupling single-cell biophysics with retinal vascular network topology and complexity

Award Number: R01EY033003

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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