■ For the first time, scientists from Regeneron and Duke University have generated a comprehensive atlas of the cells in the trabecular meshwork (TM) — the critical group of cells that regulate pressure in the eye. This seminal paper, published in Proceedings of the National Academy of Sciences, is viewed as a groundbreaking step to unlocking future treatment approaches for glaucoma. Twelve distinct cell types, along with their RNA sequences, were articulated within the TM, and now these researchers understand how healthy eyes balance pressure in the eye and what happens when glaucoma disrupts this process.

The researchers posited that the conventional outflow pathway is a complex tissue involved in maintaining IOP homeostasis. Cells that reside in the pathway have complementary roles to ensure faithful regulation of outflow resistance, and thus IOP. The researchers used single-cell RNA sequencing to generate an atlas of human conventional outflow cells to more accurately define their cellular roles based upon differential gene expression and tissue localization.

The dataset was robust, being generated from 8 individual samples from 4 human donors. These expression data more accurately and convincingly identify the various individual cell types, cell type-specific gene markers, and disease-related gene expression across the different cell types in the conventional outflow pathway.

A major outcome of the study was the identification of 12 different cell types in or adjacent to conventional outflow tissues. Importantly, the researchers clearly found that there are 2 distinct “molecular types” of TM cells with related expression patterns. They also showed in human eyes the hybrid blood vascular/lymphatic character of Schlemm’s canal, supporting mouse lineage tracing data. Finally, they demonstrated the utility of their dataset by localizing select glaucoma-related genes to specific cell populations in the outflow tract. These findings constitute the initial stage of a valuable and reliable dataset that can be used by conventional outflow researchers for years to come.