Dry eye disease (DED) is a common disease with shockingly few FDA-approved drug options, partially because of the difficulties of modeling the complex pathophysiology in human eyes. Enter the blinking eye-on-a-chip: an artificial human eye replica constructed in the laboratory of Penn Engineering researchers. Complete with a blinking eyelid, it is helping scientists and drug developers to improve their understanding and treatment of DED, among other potential uses. The research, published in Nature Medicine, outlines the accuracy of the eye-on-a-chip as an organ stand-in and demonstrates its utility as a drug testing platform.

The study was led by Penn Engineering’s Dan Huh, associate professor in the department of bioengineering, and graduate student Jeongyun Seo. They collaborated with Vivian Lee, Vatinee Bunya and Mina Massaro-Giordano from the department of ophthalmology in Penn’s Perelman School of Medicine, as well as with Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in Penn Engineering’s department of materials science and engineering. Other collaborators included Woo Byun,  Andrei Georgescu and Yoon-suk Yi, members of Dr. Huh’s lab, and Farid Alisafaei, a member of Dr. Shenoy’s lab.

To construct their eye-on-a-chip, Dr. Huh’s team starts with a porous scaffold engineered with 3D printing, about the size of a dime and the shape of a contact lens, on which they grow human eye cells. The cells of the cornea grow on the inner circle of scaffolding, dyed yellow, and the cells of the conjunctiva, the specialized tissue covering the white part of human eyes, grow on the surrounding red circle. A slab of gelatin acts as the eyelid, mechanically sliding over the eye at the same rate as human blinking. Fed by a tear duct, dyed blue, the eyelid spreads artificial tear secretions over the eye to form what is called a tear film.

Before proceeding with DED drug-testing, the team evoked DED conditions in their eye-on-a-chip by cutting their device’s artificial blinking in half and carefully creating an enclosed environment that simulated the humidity of real-life conditions. When put to the test against real human eyes, both healthy and with DED, the corresponding eye-on-a-chip models proved their similarity to the actual organ on multiple clinical measures. 

For DED drug testing, they landed on an upcoming drug based on lubricin, a protein primarily found in the lubricating fluid that protects joints. By comparing the testing results of their models of a healthy eye, an eye with DED, and an eye with DED plus lubricin, Dr. Huh and Ms. Seo were able to further scientists’ understanding of how lubricin works and show the drug’s promise as a DED treatment.

Similarly, the process of building a blinking eye-on-a-chip pushed forward scientists’ understanding of the eye itself, providing insights into the role of mechanics in biology. Collaborating with Dr. Shenoy, director of the Center for Engineering MechanoBiology, the team’s attention was drawn to how the physical blinking action was affecting the cells they cultivated to engineer an artificial eye on top of their scaffolding.

Human cornea cells growing on the scientists’ scaffold more quickly became specialized and efficient at their particular jobs when the artificial eyelid was blinking on top of them, suggesting that mechanical forces like blinking contribute significantly to how cells function. These types of conceptual advances, coupled with drug discovery applications, highlight the multifaceted value that engineered organs-on-a-chip can contribute to science. 

For the complete story, visit https://tinyurl.com/eyeonachip