Abstract
The 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.
Highlights
The 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
Elevated level of MCP-1 and IL-8 in the aqueous humor (AH) of patients with POAG as well as those with hypertensive anterior uveitis, which is characterized by sudden abrupt elevation of intraocular pressure (IOP) (Supplementary Table S1), led us to test a possible role for MCP-1 and IL-8 in TM cell actin cytoskeletal organization and focal adhesions formation
We initially examined MCP-1 and IL-8 mediated changes in actin stress fibers and MLC phosphorylation, which is a key regulator of myosin IIdriven contractile activity in human TM cells
Summary
The 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. Real-time qPCR analyses showed significant increase of FN1 and FSP1 in MCP-1 and IL-8 treated TM cells, relative to control cells (Fig. 5C). When scratched TM cells incubated with various agents, MCP-1 and IL-8 treated TM cells showed significantly increased migration activities relative to the control cells at 24 h after scratching, and this effect was further enhanced with co-treatment with TGF-β1 (Supplementary Fig S5).
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