Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork

Junglas B, Kuespert S, Seleem AA, Struller T, Ullmann S, Boesl M, Bosserhoff A, Koestle J, Wagner R, Tamm ER, Fuchshofer R (2012)

Publication Type: Journal article

Publication year: 2012

Journal

American Journal of Pathology American Society for Investigative Pathology (ASIP)

Book Volume: 180

Pages Range: 2386-2403

Journal Issue: 6

DOI: 10.1016/j.ajpath.2012.02.030

Abstract

The most critical risk factor for optic nerve damage in cases of primary open-angle glaucoma (POAG) is an increased intraocular pressure (IOP) caused by a resistance to aqueous humor outflow in the trabecular meshwork (TM). The molecular pathogenesis of this increase in outflow resistance in POAG has not yet been identified, but it may involve transforming growth factor TGF-β2, which is found in higher amounts in the aqueous humor of patients with POAG. Connective tissue growth factor (CTGF) is a TGF-β2 target gene with high constitutive TM expression. In this study, we show that either adenoviral-mediated or transgenic CTGF overexpression in the mouse eye increases IOP and leads to optic nerve damage. CTGF induces TM fibronectin and α-SMA in animals, whereas actin stress fibers and contractility are both induced in cultured TM cells. Depletion of CTGF by RNA interference leads to a marked attenuation of the actin cytoskeleton. Rho kinase inhibitors cause a reversible decline in the IOP of CTGF-overexpressing mice to levels seen in control littermates. Overall, the effects of CTGF on IOP appear to be caused by a modification of the TM actin cytoskeleton. CTGF-overexpressing mice provide a model that mimics the essential functional and structural aspects of POAG and offer a molecular mechanism to explain the increase of its most critical risk factor. © 2012 American Society for Investigative Pathology.

Involved external institutions

Universität Regensburg DE Germany (DE) Max-Planck-Institut für Neurobiologie / Max Planck Institute of Neurobiology DE Germany (DE)

How to cite

APA:

Junglas, B., Kuespert, S., Seleem, A.A., Struller, T., Ullmann, S., Boesl, M.,... Fuchshofer, R. (2012). Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork. American Journal of Pathology, 180(6), 2386-2403. https://doi.org/10.1016/j.ajpath.2012.02.030

MLA:

Junglas, Benjamin, et al. "Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork." American Journal of Pathology 180.6 (2012): 2386-2403.

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