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Human TM Cells as Models for Pseudo-Exfoliation Glaucoma (PEXG)

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Exfoliation syndrome and exfoliation glaucoma (XFG; PEXG) remain an enigma with regard to their pathogenesis and cause of glaucoma. While several studies have characterized their clinical characteristics and different phenotypic variations, the mechanisms of formation for complex protein aggregates within ocular tissues like the trabecular meshwork (TM) in this disease entity are largely unknown. The risk factors for the onset of glaucoma in XFS remain a mystery, with only selected eyes developing glaucoma or raised intraocular pressure, IOP. Several molecular markers are known to be upregulated in XFS and XFG eyes, including oxidative stress markers, cytokines, and transforming growth factor (TGF-β1). Several studies have elucidated the differences between eyes with exfoliation and primary glaucoma. Yet, the molecular events that mark the onset of XFS or the development of glaucoma are underinvestigated. This is largely because of the inability to sample ocular tissue like the TM or iris in early disease stages. The variable viability of cells from tissues obtained during surgery is a concern precluding easy understanding of the events involved specifically in this disease. In vitro human TM cell line models mimicking this disease allow us to study the temporal events that may mimic the disease's onset and progression over time. We herein present the protocols for establishing such an in vitro model for the study of exfoliation syndrome or XFG, which may be valuable for evaluating various molecular events responsible for the disease pathogenesis.

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