Glaucoma silently steals vision from millions of people worldwide. Here's how we're working to stop it.
Glaucoma describes a group of potentially blinding ocular disorders that represent the leading cause of irreversible blindness worldwide. Approximately 80 million people currently live with this disease — a number projected to rise to 111 million by 2040 as the world’s population ages [PMID: 27764086]. Of those affected, 8.4 million are blind or seriously visually impaired today, a figure expected to reach 22 million by 2040. Within the glaucoma field, our lab focuses on the following research areas:
Research into Aqueous Humor Dynamics
A key risk factor for glaucoma is elevated intraocular pressure (IOP), which is determined by the flow of aqueous humor (AH) through two specialized ocular structures: the trabecular meshwork (TM) and Schlemm’s canal (SC), located at the chamber angle of the eye (Figs. 1 and 2). In glaucoma, resistance to AH outflow through the TM and SC is increased, resulting in elevated IOP. However, the precise molecular mechanisms underlying this increased resistance remain incompletely understood. The Ethier Lab is pursuing multiple complementary research directions to define the relationship between molecular changes, IOP elevation, and outflow resistance — with the ultimate goal of identifying and testing new therapies to prevent IOP elevation and halt glaucoma progression.
A) Stem Cell Therapies for Trabecular Meshwork Regeneration
Trabecular meshwork cellularity declines with age — and even more markedly in individuals with glaucoma [PMID: 7298275]. This progressive cell loss is thought to contribute to the increased outflow resistance and elevated IOP that characterize the disease. Restoring TM cellularity through a cell-based therapy therefore represents a promising — and currently unmet — therapeutic strategy. In response to this need, we have developed approaches to replenish TM cellularity and lower IOP [PMID: 40622256] and are now working to translate these basic science advances into a clinically viable treatment.
B) Trabecular Meshwork/Schlemm’s Canal Stiffness and Mechanobiology
Like many other cell types [PMID: 16293750], the gene and protein expression profiles of TM and SC cells are sensitive to the mechanical properties of their surrounding matrix. Abnormal protein deposition within the TM alters outflow resistance and contributes to IOP elevation [PMIDs: 18235007, 8641839]. We and others have characterized the stiffness of TM tissue and SC cells in both normal and glaucomatous eyes using atomic force microscopy and inverse finite element modeling [PMIDs: 29643342, 28973327, 38648717, 25201985]. We have found that SC cells from glaucomatous eyes exhibit altered molecular and functional phenotypes compared to cells from non-glaucomatous eyes [PMIDs: 41411132, 41022289] — a finding we are leveraging to identify novel anti-glaucoma therapeutic targets.