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Decoding Curvature-Dependent Keratoconus Pathology Using an Engineered Human Cornea Chip

Award Number: R01EY037789
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2030

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Decoding Curvature-Dependent Keratoconus Pathology Using an Engineered Human Cornea Chip - Project Summary Keratoconus (KC) is a progressive corneal disorder affecting millions worldwide, characterized by corneal thinning, protusion, and irregular astigmatism. Despite its prevalence, the precise mechanisms underlying KC remain unclear, hindering the development of effective treatments beyond corneal cross-linking and transplantation. This project aims to develop an advanced in vitro KC model using a microfabricated organ chip platform, addressing the limitations of current animal models and providing a more accurate, ethically sound, and controllable platform for studying KC pathogenesis. Our approach will establish an anatomically and physiologically relevant cornea chip, providing experimental access to mechanistic investigations of interactions between corneal epithelial, stromal, and endothelial cells in the context of KC. The project consists of three specific aims: 1) Investigate curvature-dependent cellular responses in epithelial, stromal, and endothelial cells using a curvature array chip, identifying mechanotransduction pathways driving pathological reprogramming and validating therapeutic targets through gene knockout studies; 2) Engineer biomimetic interfacial membranes (epithelial basement membrane and Descemet's membrane) using co-culture approaches to investigate how geometric stress concentrations disrupt membrane integrity and distinguish active pathway-mediated from passive mechanical damage; and 3) Develop an integrated multi-layer cornea chip with controllable curvature to investigate mechanobiological crosstalk, validate the platform comprehensively, and test therapeutic interventions targeting mechanotransduction and matrix degradation pathways at different disease stages. By combining expertise in bioengineering, ophthalmology, and corneal biology, this project aims to create a physiologically relevant KC model that will advance our understanding of the perpetuation cycle mechanisms, identify mechanobiological tipping points, and facilitate the discovery of therapeutic targets for interrupting this progressive corneal disorder.


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 = $620,926 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Vision Research	000	1	8/31/2026	NEW	$620,926
														Subtotal = $620,926

Grand Total All Awards = $620,926

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Decoding Curvature-Dependent Keratoconus Pathology Using an Engineered Human Cornea Chip

Award Number: R01EY037789

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2030

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