scholarly journals Effects of Pharmacologic Inhibition of Protein Geranylgeranyltransferase Type I on Aqueous Humor Outflow through the Trabecular Meshwork

2008 ◽  
Vol 49 (6) ◽  
pp. 2464 ◽  
Author(s):  
P. Vasantha Rao ◽  
Yuri K. Peterson ◽  
Toshihiro Inoue ◽  
Patrick J. Casey
Keyword(s):  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Type I ◽  
Aqueous Humor Outflow ◽  
Pharmacologic Inhibition

3230 Cell-Matrix and Cell-Cell Interactions and the Aqueous Humor Outflow In Trabecular Meshwork (TM) Cells

SciVee ◽  
2012 ◽  
Author(s):  
Xinbo Li ◽  
Diala Abu-Hassan ◽  
Janice Vranka ◽  
John Bradley ◽  
Ted Acott ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Cell Interactions ◽  
Aqueous Humor Outflow ◽  
Cell Matrix ◽  
Cell Cell

scholarly journals Cell-Based Therapies for Trabecular Meshwork Regeneration to Treat Glaucoma

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1258
Author(s):  
Shayshadri Mallick ◽  
Malini Sharma ◽  
Ajay Kumar ◽  
Yiqin Du
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Normal Pressure ◽  
Aqueous Humor Outflow ◽  
Current Therapies ◽  
Normal Pressure Glaucoma ◽  
Matrix Accumulation

Glaucoma is clinically characterized by elevated intraocular pressure (IOP) that leads to retinal ganglion cell (RGC) and optic nerve damage, and eventually blindness if left untreated. Even in normal pressure glaucoma patients, a reduction of IOP is currently the only effective way to prevent blindness, by either increasing aqueous humor outflow or decreasing aqueous humor production. The trabecular meshwork (TM) and the adjacent Schlemm’s canal inner wall play a key role in regulating IOP by providing resistance when aqueous humor drains through the tissue. TM dysfunction seen in glaucoma, through reduced cellularity, abnormal extracellular matrix accumulation, and increased stiffness, contributes to elevated IOP, but current therapies do not target the TM tissue. Stem cell transplantation for regeneration and re-functionalization of damaged TM has shown promise in providing a more direct and effective therapy for glaucoma. In this review, we describe the use of different types of stem cells for TM regeneration in glaucoma models, the mechanisms of regeneration, and the potential for glaucoma treatment using autologous stem cell transplantation.

scholarly journals Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork

2008 ◽  
Vol 295 (5) ◽  
pp. C1057-C1070 ◽  
Author(s):  
Min Zhang ◽  
Rupalatha Maddala ◽  
Ponugoti Vasantha Rao
Keyword(s):  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Rho Gtpase ◽  
Cytoskeletal Proteins ◽  
Fiber Formation ◽  
Aqueous Humor Outflow ◽  
Ecm Proteins ◽  
Rhoa Gtpase ◽  
Cell Adhesive ◽  
Adhesive Interactions

Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, is poorly understood. The role of RhoA GTPase-mediated actomyosin organization, cell adhesive interactions, and gene expression in regulation of aqueous humor outflow was investigated using adenoviral vector-driven expression of constitutively active mutant of RhoA (RhoAV14). Organ-cultured anterior segments from porcine eyes expressing RhoAV14 exhibited significant reduction of aqueous humor outflow. Cultured TM cells expressing RhoAV14 exhibited a pronounced contractile morphology, increased actin stress fibers, and focal adhesions and increased levels of phosphorylated myosin light chain (MLC), collagen IV, fibronectin, and laminin. cDNA microarray analysis of RNA extracted from RhoAV14-expressing human TM cells revealed a significant increase in the expression of genes encoding extracellular matrix (ECM) proteins, cytokines, integrins, cytoskeletal proteins, and signaling proteins. Conversely, various ECM proteins stimulated robust increases in phosphorylation of MLC, paxillin, and focal adhesion kinase and activated Rho GTPase and actin stress fiber formation in TM cells, indicating a potential regulatory feedback interaction between ECM-induced mechanical strain and Rho GTPase-induced isometric tension in TM cells. Collectively, these data demonstrate that sustained activation of Rho GTPase signaling in the aqueous humor outflow pathway increases resistance to aqueous humor outflow through the trabecular pathway by influencing the actomyosin assembly, cell adhesive interactions, and the expression of ECM proteins and cytokines in TM cells.

scholarly journals Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow

2011 ◽  
Vol 227 (1) ◽  
pp. 172-182 ◽  
Author(s):  
Ang Li ◽  
Chi Ting Leung ◽  
Kim Peterson-Yantorno ◽  
W. Daniel Stamer ◽  
Claire H. Mitchell ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Atp Release ◽  
Aqueous Humor Outflow ◽  
Trabecular Meshwork Cells

scholarly journals Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiyoung Lee ◽  
Jin A. Choi ◽  
Hyun-hee Ju ◽  
Ju-Eun Kim ◽  
Soon-Young Paik ◽  
...  
Keyword(s):  
Viral Infection ◽  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Anterior Uveitis ◽  
Rho Gtpase ◽  
Open Angle Glaucoma ◽  
Focal Adhesions ◽  
Aqueous Humor Outflow ◽  
Trabecular Meshwork Cells ◽  
Aqueous Outflow

AbstractThe inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.

Sign in / Sign up

Export Citation Format

Share Document