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Updated: Jun 14, 2026
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Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis
Published on: June 3, 2018
Modeling of Lowe Patient-Derived Induced Pluripotent Stem Cells Into Trabecular Meshwork.
Yang Sun1, Tia J Kowal2, Yingchun Shen2
1From the Department of Ophthalmology (Y.S., T.J.K., Y.S., J.Z., B.W., C.H.L.), Stanford University School of Medicine, Palo Alto, California, USA; Palo Alto Veterans Administration (Y.S.), Palo Alto, California, USA.
American Journal of Ophthalmology
|June 12, 2026
Summary
Researchers developed patient-derived trabecular meshwork cells to study Lowe syndrome (LS) glaucoma. OCRL deficiency in these cells revealed defects in phagocytosis, cilia, and lysosome function, offering new models for LS research.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Congenital glaucoma is a leading cause of vision loss in Lowe syndrome (LS), a rare X-linked disorder.
- Mutations in the OCRL gene cause LS, but glaucoma pathogenesis remains unclear due to limited patient ocular cell access.
Purpose of the Study:
- To establish and functionally characterize patient-derived induced human trabecular meshwork (iHTM) cell lines.
- To investigate the cellular mechanisms underlying glaucoma in Lowe syndrome.
Main Methods:
- Generated induced pluripotent stem cell (iPSC)-derived iHTM cell lines from an LS patient (LS100) and a healthy sibling (LS200).
- Evaluated stem cell and trabecular meshwork markers using immunoblot and immunostaining.
- Assessed cellular functions including response to dexamethasone, phagocytosis, primary cilia length, and lysosome positioning.
Main Results:
- iHTM cells expressed trabecular meshwork markers and showed TM-like responses.
- LS100-iHTM cells exhibited shortened primary cilia and reduced Gli1 expression compared to LS200-iHTM.
- LS100-iHTM cells displayed increased perinuclear lysosome clustering, suggesting impaired nutrient sensing.
Conclusions:
- Established functional iHTM cell lines from LS patient and sibling iPSCs.
- OCRL deficiency in LS alters pathways involved in phagocytosis, ciliogenesis, and lysosome positioning.
- These iHTM models retain LS-associated defects and are valuable for future mechanistic and therapeutic studies.
