'Eye-on-a-chip' Uncovers Mechanism Behind Steroid-Induced Glaucoma
Cornell researchers have unveiled a cutting-edge 3D eye-on-a-chip model that identifies how steroids can trigger glaucoma by disrupting eye fluid drainage, opening new pathways for targeted treatments.
Researchers at Cornell University have developed an innovative 3D 'eye-on-a-chip' model to better understand the mechanisms leading to steroid-induced glaucoma, a serious condition that can cause irreversible vision loss. This groundbreaking platform mimics the complex flow of ocular fluids within the eye, specifically focusing on the drainage system responsible for maintaining intraocular pressure.
Glaucoma occurs when fluid drainage is blocked or impaired, causing pressure to build up and damaging the optic nerve. While steroids are commonly prescribed for anti-inflammatory purposes in eye treatments, they can inadvertently exacerbate this condition. Until now, the precise biological processes why steroids trigger glaucoma remained unclear.
The team constructed a dual-layered microphysiological system replicating the trabecular meshwork (TM) and Schlemm’s canal (SC), two critical components of the eye's lymphatic-like drainage system. When treated with dexamethasone, an anti-inflammatory steroid, the system revealed a significant increase in outflow resistance. The key culprit identified was the receptor ALK5 in TM cells. Activation of ALK5 led to the downregulation of VEGFC, a protein essential for maintaining the proper junctions between endothelial cells in the SC.
This disruption causes the junctions to thicken or tighten, impeding fluid outflow and elevating intraocular pressure—an essential factor in glaucoma development. These findings were validated in mouse models, underscoring the significance of the mechanism.
The discovery opens up new therapeutic avenues: blocking ALK5 activity or supplementing VEGFC could prevent or mitigate steroid-induced glaucoma. This research highlights the importance of targeted therapies and demonstrates the potential of advanced 3D organ models to unravel complex eye diseases.
The study was published in Nature Cardiovascular Research, led by Dr. Renhao Lu. The development of this eye-on-a-chip exemplifies how bioengineering approaches can provide deeper insights into disease mechanisms and foster the creation of more effective treatments.
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