Junglas, Benjamin and Kuespert, Sabrina and Seleem, Amin A. and Struller, Tobias and Ullmann, Sabrina and Boesl, Michael and Bosserhoff, Anja and Koestle, Josef and Wagner, Ralf and Tamm, Ernst R. and Fuchshofer, Rudolf (2012) Connective Tissue Growth Factor Causes Glaucoma by Modifying the Actin Cytoskeleton of the Trabecular Meshwork. AMERICAN JOURNAL OF PATHOLOGY, 180 (6). pp. 2386-2403. ISSN 0002-9440,
Full text not available from this repository. (Request a copy)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-beta 2, which is found in higher amounts in the aqueous humor of patients with POAG. Connective tissue growth factor (CTGF) is a TGF-beta 2 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 RV and leads to optic nerve damage. CTGF induces TM fibronectin and alpha-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. (Am J Pathol 2012, 180:2386-2403; http://dx.doi.org/10.1016/j.ajpath.2012.02.030)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AQUEOUS-HUMOR OUTFLOW; OPEN-ANGLE GLAUCOMA; EXTRACELLULAR-MATRIX TURNOVER; OCULAR HYPERTENSION TREATMENT; NORMAL-TENSION GLAUCOMA; INTRAOCULAR-PRESSURE; STRESS FIBERS; OPTIC-NERVE; ELECTRON-MICROSCOPY; MECHANICAL-STRESS; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2020 04:53 |
| Last Modified: | 13 May 2020 04:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18638 |
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