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Single-cell characterization of anterior segment development in the mouse reveals the cell types, pathways, and signals driving formation of the trabecular meshwork and Schlemm's canal.

Revathi Balasubramanian | Nicholas Tolman | Taibo Li | Abdul Hannan | Violet Bupp-Chickering | Karina Polanco | Aakriti Bhandari | Sally Zhou | Marina Simón | John Peregrin | Christa Montgomery | Krishnakumar Kizhatil | Jiang Qian | Simon W M John
eLife | 2026

Morphogenesis of the anterior segment (AS) is crucial for healthy ocular physiology and vision, but is only partially understood. The Schlemm's canal (SC) and trabecular meshwork (TM) are essential drainage tissues within the AS, and their proper development and function are critical for maintaining normal intraocular pressure; abnormalities in either tissue can result in elevated pressure and glaucoma. Here, we use single-cell transcriptomic profiling to provide high-resolution molecular detail of mouse AS development with a particular focus on SC and TM. We report transcriptomes for ~130,000 single cells at key developmental stages from postnatal day 2 (P2) to P60. We provide the first annotation of cell types across these developmental stages and crucial information about dynamic changes in pathways/gene expression. Further, we trace developmental trajectories for TM cell and SC endothelial cell (SEC) subtypes and determine genes and signaling networks driving their specific cell fates. We demonstrate dynamic changes in signaling interactions between SC and the TM cells during their synchronized development. Collectively, our data lay a deep molecular foundation for AS development that will direct understanding of normal ocular physiology, glaucoma, and other AS conditions.

Pubmed ID: 42478926

Associated grants

  • Agency: BrightFocus Foundation,
    Id: G2021007S
  • Agency: NEI NIH HHS, United States
    Id: R01EY018606
  • Agency: NEI NIH HHS, United States
    Id: R01EY032062
  • Agency: NEI NIH HHS, United States
    Id: R01EY034493
  • Agency: NEI NIH HHS, United States
    Id: R01EY032507
  • Agency: NEI NIH HHS, United States
    Id: R01EY011721
  • Agency: BrightFocus Foundation,
    Id: CG2020004
  • Agency: Glaucoma Research Foundation,
    Id: ShafGrnt2024BalaReva
  • Agency: New York Fund for Innovation in Research and Scientific Talent,
    Id: NYFIRST - EMPIRE CU19-2660
  • Agency: Columbia University,
    Id: Precision Medicine Initiative
  • Agency: Columbia University,
    Id: P30EY019007
  • Agency: Johns Hopkins University,
    Id: P30EY00176

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