Study Reveals Potential Therapeutic Target for Treating Glaucoma
US researchers have mapped the cellular diversity of the trabecular meshwork, identifying a previously unrecognized cell subtype that may contribute to glaucoma progression and respond to vitamin B3 treatment. The study represents a significant advance in understanding trabecular meshwork cell heterogeneity and its role in intraocular pressure regulation and glaucoma.
Scientists have identified a metabolically sensitive cell subtype in the trabecular meshwork which shows early signs of dysfunction in a genetic mouse model of glaucoma.
The study, published in eLife in January 2026 provides, according to the editors, fundamental findings that highlight a potential therapeutic strategy for preventing or slowing the development of glaucoma. The study was co-led by Duke Eye Center resesearcher, W. Daniel Stamer, PhD, Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology and Vice Chair for Basic Science Research.
Detailed molecular map of the trabecular meshwork
One of the main risk factors of glaucoma is high intraocular pressure, which often results from dysfunction in the trabecular meshwork. “Despite its importance, little is known about the cellular diversity within the trabecular meshwork, or how individual subtypes of these cells are susceptible to dysfunction,” says co-lead author Nicholas Tolman, a Postdoctoral Research Scientist in the Department of Ophthalmology, Columbia University Vagelos College of Physicians and Surgeons, New York, US. “We set out to create a detailed molecular map of the trabecular meshwork and to identify the cells most affected in glaucoma.”
Tolman and colleagues used single-cell RNA sequencing to profile nearly 18,000 cells from the limbal region of two strains of healthy mice. They identified six major cell types, with further analysis revealing three subtypes of trabecular meshwork cells, which they named TM1, TM2 and TM3. The identities of these subtypes were confirmed across multiple datasets, laboratories, and through immunofluorescence – which uses glowing tags to visualise specific proteins – and in situ hybridisation, which shows where particular genes are active in a tissue.
Each TM subtype showed distinct molecular signatures and spatial organisation. TM1 cells were enriched for genes that are crucial for extracellular matrix production, suggesting a role in maintaining tissue structure. TM2 cells expressed genes linked to cell signalling and phagocytosis – a process where a cell engulfs and internalises foreign particles – hinting at a role in immune response and debris clearance. TM3 cells stood out for their high levels of mitochondrial and contractility-related genes, as well as elevated expression of Lmx1b, a gene previously linked to glaucoma in both mice and humans.
Signs of mitochondrial dysfunction
To investigate how these subtypes respond to glaucoma-associated stress, the team used a mouse model carrying a dominant mutation in Lmx1b, mimicking genetic glaucoma. While all three TM subtypes were present in these mice, TM3 cells were most affected. They showed signs of mitochondrial dysfunction, reduced oxidative phosphorylation (a key energy-producing pathway), and lower expression of genes involved in protein quality control. These disruptions likely impair the function and health of TM3 cells, affecting their ability to properly regulate outflow and pointing to TM3 as a critical cell type in glaucoma progression.
“While our work shows a clear effect of the Lmx1b mutation on mitochondria, future studies will be needed to see if and how Lmx1b directly modulates mitochondrial genes in mutant TM cells,” Tolman says.
Vitamin B3 led to lower eye pressure
Finally, the team tested whether supporting mitochondrial function could help protect the eye from glaucoma progression. They treated some of the mice with nicotinamide, a form of vitamin B3 known to enhance cellular metabolism and improve resilience. This led to lower eye pressure and fewer signs of the anatomical changes linked to glaucoma progression, compared to the mice that did not receive treatment. These results suggest that supporting TM3 cells metabolically could offer a new avenue to prevent or slow glaucoma development, although more studies are needed to validate the findings and provide a fuller mechanistic understanding of vitamin B3’s therapeutic effects.
“Our study provides a comprehensive characterisation of mouse trabecular meshwork cells, offering much-needed information on the cell subtypes that are dysregulated in glaucoma,” says senior author Simon John, Professor in the Department of Ophthalmology, Columbia University Vagelos College of Physicians and Surgeons, and the Zuckerman Mind Brain Behavior Institute, Columbia University. “These insights could lead to new therapies that target the cells most vulnerable to damage, potentially preventing or delaying vision loss. It will be interesting to determine whether similar cell types exist in the human eye and whether interventions like nicotinamide could offer lasting protection in clinical settings.”
Nicholas Tolman, Taibo Li, Revathi Balasubramanian, Guorong Li, Rebecca Pfeiffer, Violet Bupp-Chickering, Ruth A Kelly, Marina Simón, John Peregrin, Christa Montgomery, Bryan Jones, W Daniel Stamer, Jiang Qian, Simon WM John (2026) Single-cell profiling of trabecular meshwork identifies mitochondrial dysfunction in a glaucoma model that is protected by vitamin B3 treatment
eLife 14:RP107161. https://doi.org/10.7554/eLife.107161.3