JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Hyaluronan cable formation by ocular trabecular meshwork cells.

Hyaluronan (HA) in the ocular trabecular meshwork (TM) is a critical modulator of aqueous humor outflow. Individual HA strands in the pericellular matrix can coalesce to form cable-like structures, which have different functional properties. Here, we investigated HA structural configuration by TM cells in response to various stimuli known to stimulate extracellular matrix (ECM) remodeling. In addition, the effects of HA cable induction on aqueous outflow resistance was determined. Primary TM cell cultures grown on tissue culture-treated plastic were treated for 12-48 h with TNFα, IL-1α, or TGFβ2. TM cells grown on silicone membranes were subject to mechanical stretch, which induces synthesis and activation of ECM proteolytic enzymes. HA structural configuration was investigated by HA binding protein (HAbp) staining and confocal microscopy. HAbp-labeled cables were induced by TNFα, TGFβ2 and mechanical stretch, but not by IL-1α. HA synthase (HAS) gene expression was quantitated by quantitative RT-PCR and HA concentration was measured by ELISA assay. By quantitative RT-PCR, HAS-1, -2, and -3 genes were differentially up-regulated and showed temporal differences in response to each treatment. HA concentration was increased in the media by TNFα, TGFβ2 and IL-1α, but mechanical stretch decreased pericellular HA concentrations. Immunofluorescence and Western immunoblotting were used to investigate the distribution and protein levels of the HA-binding proteins, tumor necrosis factor-stimulated gene-6 (TSG-6) and inter-α-inhibitor (IαI). Western immunoblotting showed that TSG-6 and IαI were increased by TNFα, TGFβ2 and IL-1α, but mechanical stretch reduced their levels. The underlying substrate appears to affect the identity of IαI·TSG-6·HA complexes since different complexes were detected when TM cells were grown on a silicone substrate compared to a rigid plastic surface. Porcine anterior segments were perfused with 10 μg/ml polyinosinic:polycytidylic acid (polyI:C), a potent inducer of HA cables, and outflow rates were monitored for 72 h. PolyI:C had no significant effect on outflow resistance in porcine anterior segments perfused at physiological pressure. Collectively, HAS gene expression, HA concentration and configuration are differentially modified in response to several treatments that induce ECM remodeling in TM cells. In ocular TM cells, our data suggests that the most important determinant of HA cable formation appears to be the ratio of HA chains produced by the different HAS genes. However, the act of rearranging pericellular HA into cable-like structures does not appear to influence aqueous outflow resistance.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app