Human Trabecular Meshwork Cells: HTMC

Human Trabecular Meshwork Cells (HTMC) are endothelial-like cells in a sponge-like connective tissue located near the front of the eye.  HTMC make layers of beams, part of a fibrous basement membrane containing extracellular matrix and cells.  In this area of high outflow resistance, HTMC regulate eye pressure by controlling drainage of fluid into tubes that flow into the bloodstream.  Outflow is mediated by alterations in contractility and tension of HTMC, which also serve as a self-cleaning filter due to their phagocytic nature.  Live cell imaging of the cytoskeleton provides valuable information on actin dynamics in HTMC.  Other research aims to identify treatments that relax HTMC contraction to increase fluid outflow and lower eye pressure.  Specific targeting of HTMC could also play a clinical role by increasing therapeutic efficacy of nanoparticles for gene delivery.

Damage and dysfunction of HTMC have clinical significance.  For instance, hypoxia increases DNA methylation, accompanied by altered gene expression.  During the normal aging process, HTMC number decreases, and senescent cells accumulate.  In glaucoma, a leading cause of irreversible blindness, decreased fluid outflow causes an elevation of intraocular pressure and progressive loss of retinal ganglion cells.  Physical changes to the TM include increased fibrosis, fibronectin accumulation, and expression of ECM cross-linking enzymes.  This cytoskeletal reorganization and cell loss causes the TM to become rigid and stiff.  Other glaucoma-related dysfunctions include mitochondrial defects, altered signaling pathways, elevated TGF-β2, genomic DNA defects, and oxidation damage. 

Myocilin expression in Trabecular Meshwork Cells was analyzed following dexamathone treatment. After cells reach 70-80% confluency, HTMC cells were treated with 100nM and 500nM of dexamethasone for 6 days in DMEM with 1% FBS. Cell lysates were analyzed for Myocilin and beta-Actin expression by Western Blot.