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 stress. 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.

Keywords: Cell culture; Cellular phenotype; Glaucoma; Trabecular meshwork.

Figure 1

Morphology and response to corticosteroid of human trabecular meshwork cell monolayers in culture. Panel A shows phase contrast and immunofluorescence microscopic images of three human trabecular meshwork cell monolayers, each isolated from different human donor eyes and displaying different morphologies. HTM 94 shows predominant “endothelial-like” morphology, while HTM120 and HTM86 are mixed cultures with primarily “myofibroblast” morphologies. Cell monolayers were probed with antibodies raised against myocilin in the presence or absence of 100 nM dexamethasone (DEX) treatment for 5 days. To assess magnitude of myocilin induction, corresponding western blots of treated and untreated TM cell monolayers are shown in panel B.

Figure 2

Morphological comparison between transformed GTM3 cells and primary cultures of human TM cells. GTM3 cells (A-10X and B-40X) are smaller cells with less cytoplasm and continue cell division (rounded cells) despite being confluent. Primary human TM cells (NTM176-04)(C-10X and D-40X) are larger and more elongated with overlapping processes. These cells are contact inhibited and stop dividing when they become a confluent monolayer.

Figure 3

Morphology and corticosteroid response of a commercial human “trabecular meshwork” cell (HTM) culture compared to a human trabecular meshwork cell strain isolated in an academic setting. The phase contrast images show subtle phenotypic differences; however, western blot analysis of myocilin show clear differences in both basal expression and induction by dexamethasone (DEX).