Approximately 1 in 350 people worldwide have keratoconus and similar eye diseases that impair vision when the cornea loses its normal shape.
Publishing in Nature Communications, researchers at the University of Utah’s John and Marcia Price College of Engineering and John A. Moran Eye Center have made a discovery about keratoconus and other ectatic eye diseases that changes our understanding of them. The study reveals the abnormal corneal curvature found in these diseases is not merely a consequence of disease but an active driver of pathological progression.
“This discovery fundamentally reframes how we understand these eye diseases and how we could treat them,” says study lead author Jungkyu “Jay” Kim, associate professor in the Department of Mechanical Engineering.
Doctors treat keratoconus and other conditions with special contact lenses or implants to shape the cornea, or corneal transplants in severe cases. The study, conducted using a cornea-on-a-chip device developed by Kim, opens the door to new, non-surgical therapies that could target how cells in the eye sense and respond to pressure.
“The study provides new insight into how the tiny internal structures that give corneal cells their shape and strength, the cytoskeleton, are organized and how they differ in sensing pressure across the layers of the cornea,” explains Moran Eye Center scientist David Krizaj, PhD, a study author and collaborator whose lab has also studied how cells in the eye sense pressure in the context of glaucoma. “If we can block pressure signaling early, we might prevent disease progression altogether.”
Using a hydraulically-controlled “cornea-on-a-chip” platform that can replicate the changing shape of this tissue, the team demonstrated that geometric stress alone—without any chemical stimulation—is sufficient to trigger the complete cascade of cellular changes characteristic of corneal ectatic diseases.
The researchers isolated the role curvature geometry played by utilizing a microfabricated chip platform that can closely replicate conditions across multiple parts of the cornea. On the chip, the researchers culture living corneal cells on top of flexible silicon-based membranes. These membranes can be hydraulically inflated with precise control, matching the curvature of the cornea at various stages of disease progression.
“We’ve created the first lab-grown corneal model that truly mimics keratoconus,” says Minju Kim, the study’s lead author. “Our results show that abnormal corneal curvature generates excessive mechanical stress, triggering disease pathways that transform normal cells into overactive ones that progressively distort and weaken the cornea.”
Organ-on-a-chip technologies are part of a growing movement toward “NAM” — Novel Alternative Methods — for biomedical research that do not rely on animal models. The curvature array chip, together with Kim’s previously developed cornea chip showing physiologically relevant tear flow conditions, represents a leap forward by allowing researchers to test ocular drugs and understand mechanisms of various corneal diseases.
The findings reveal specific therapeutic targets for non-surgical treatment: mechanotransduction pathways that could be targeted pharmacologically. The team is now testing these drug candidates in their cornea-on-a-chip platform to develop topical formulations that could halt keratoconus before irreversible damage occurs.
Kanghoon Choi, a member of the Kim lab, contributed to the research. This work by Kim and Krizaj was supported by an Ascender Grant from the University of Utah Research Foundation, National Institutes of Health grants UL1TR002538, R01EY022076, P30EY014800, and an Unrestricted Grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences at the University of Utah