An Integrated muti-omics cell atlas of the human trabecular meshwork and ciliary body

Jian, J.; Bao, X.; Wang, J.; Zheng, Y.; Li, J.; Shao, J.; Yang, T.; Yaman, I.; Chen, H.; Tolman, N.; Scheuermann, R. H.; Zheng, J. J.; Sheridan, C.; Liu, Y.; Du, Y.; Balasubramanian, R.; Zode, G. S.; John, S.; Stout, J. T.; Stamer, D.; Li, Y.; Chen, R.

doi:10.64898/2026.06.17.732980

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bioRxiv · 10.64898/2026.06.17.732980

An Integrated muti-omics cell atlas of the human trabecular meshwork and ciliary body

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Abstract

The trabecular meshwork (TM) and ciliary body (CB) regulate aqueous humor dynamics and intraocular pressure (IOP), and TM/Schlemms canal (SC) dysfunction underlies glaucoma. Here, we present a spatially resolved multi-omics atlas of human TM and CB, integrating snRNA-seq, scRNA-seq, and snATAC-seq from over one million cells and nuclei across 112 donors with Xenium spatial transcriptomics. We identified 9 major cell classes and 21 cell types, revealing heterogeneity, including undercharacterized fibroblast and epithelial subpopulations. Spatial mapping supported TM fibroblast zonation and CB epithelial organization. Regulatory analyses identified cell type-specific programs, including OTX/PAX networks in CB epithelium and SMAD3/TGF-{beta} signaling in fibroblasts. Integration with glaucoma loci showed enrichment of non-coding variants in regulatory elements associated with POAG and PACG. Age- and ancestry-associated remodeling revealed divergent fibroblast aging with increased PIEZO1, suggesting impaired outflow and elevated IOP. Together, this high-resolution atlas links cellular, regulatory, and genetic variation to anterior segment function and glaucoma susceptibility.

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Jian, J., Bao, X., Wang, J., Zheng, Y., Li, J., Shao, J., Yang, T., Yaman, I., Chen, H., Tolman, N., Scheuermann, R. H., Zheng, J. J., Sheridan, C., Liu, Y., Du, Y., Balasubramanian, R., Zode, G. S., John, S., Stout, J. T., Stamer, D., Li, Y., Chen, R.. 2026-06-22. An Integrated muti-omics cell atlas of the human trabecular meshwork and ciliary body. https://doi.org/10.64898/2026.06.17.732980

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