The many faces of the trabecular meshwork cell

Abstract

With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The trabecular meshwork (TM) cell at the irido-corneal angle, which is a key regulator of intraocular pressure, is no exception. Examination of cells in culture isolated from the human TM has shown that they are unique in many ways, displaying characteristic features of several different cell types. Thus, these neural crest derived cells display expression patterns and behaviors typical of endothelia, fibroblasts, smooth muscle and macrophages, owing to the multiple roles and two distinct environments where they operate to maintain intraocular pressure homeostasis. In most individuals, TM cells function normally over a lifetime in the face of persistent stressors, including phagocytic, oxidative, mechanical and metabolic stresses. Study of TM cells isolated from ocular hypertensive eyes has shown a compromised ability to perform their daily duties. This review highlights the many responsibilities of the TM cell and its challenges, progress in our understanding of TM biology over the past 30 years, as well as discusses unanswered questions about TM dysfunction that results in IOP dysregulation and glaucoma.

Life under pressure: The role of ocular cribriform cells in preventing glaucoma

“…Due to very similar expression patterns and lack of differential markers, evidence suggest that JCT and TM cells are the same cell “type”, but JCT cells may be a differentiated form of TM cells, assuming unique responsibilities based on their location and role in resistance generation. (Stamer and Clark, 2016) This is in agreement with their common embryological origin at the neural crest evidenced by immunohistochemical studies. (Keller and Acott, 2013; Overby et al, 2009; Rasmussen and Kaufman, 2014; Stamer and Acott, 2012; Tripathi and Tripathi, 1989) We hypothesize that a combination of local stimuli such as ECM substrates, soluble factors and/or mechanical stress induces a differentiation of TM cells to a JCT phenotype.…”

“…TM cells have been isolated and cultured over the last 40 years(Polansky et al, 1979; Rohen et al, 1982, 1975; Stamer and Clark, 2016), with efforts attempting to identify specific JCT cell subcultures that were first described in the 1980’s. (Rohen et al, 1982) JCT cells show higher growth kinetics than corneoscleral cells isolated from dissected TM tissue, which means that they are likely the major cellular component of “mixed TM” cell cultures.…”

“…(Perkumas and Stamer, 2012; Stamer et al, 1998) In contrast, both JCT and TM cells display induction of myocilin protein with dexamethasone treatment. (Stamer and Clark, 2016)…”

CRISPR-Cas9–based treatment of myocilin-associated glaucoma

“…Human TM cells were isolated from carefully dissected human TM tissue explants derived from patients with glaucoma or from normal donors and characterized as described previously (44). All donor tissues were obtained from regional eye banks after receipt of informed consent from the donors' families and were managed according to the guidelines in the Declaration of Helsinki on research involving human tissue.…”

Dexamethasone-Induced Ocular Hypertension in Mice

“…GCs alter TM cellular functions, including increased TM cell and nucleus sizes, inhibition of cell proliferation and migration, and altered cellular junctional complexes. 11,12 GCs reorganize the TM cell actin cytoskeleton by forming cross-linked actin networks, 13e16 which are geodesic dome-like structures and/or tangles of actin filaments. These morphological and biochemical changes alter TM stiffness and impair TM functions, such as phagocytosis, 17 31e38 Because GC treatment induces MYOC expression in TM cells, it was hypothesized that increased myocilin accumulation in the TM leads to blockage of aqueous humor flow, causing increased IOP and steroid-induced glaucoma.…”