Fuchshofer, Rudolf and Kuespert, Sabrina and Junglas, Benjamin and Tamm, Ernst R. (2014) The Prostaglandin F-2 alpha Analog Fluprostenol Attenuates the Fibrotic Effects of Connective Tissue Growth Factor on Human Trabecular Meshwork Cells. JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 30 (2-3). pp. 237-245. ISSN 1080-7683, 1557-7732
Full text not available from this repository. (Request a copy)Abstract
Purpose: The trabecular meshwork (TM) outflow pathways of the aqueous humor show an increase in extracellular matrix in patients with primary open-angle glaucoma (POAG). The increase in TM extracellular matrix appears to be caused by transforming growth factor-beta signaling and its downstream mediator connective-tissue growth factor (CTGF). Here we studied whether treatment with the prostaglandin F2 alpha analog fluprostenol modulates the CTGF-mediated increase of the TM extracellular matrix. Methods: Human TM cells from 3 different donors were treated with CTGF (50 ng/mL) and/or fluprostenol (10(-6) M and 10(-7) M) and were analyzed by real-time reverse transcription polymerase chain reaction and Western blotting. Cell supernatants of the treated cells were analyzed by zymography. Results: Treatment with CTGF induced the expression and synthesis of CTGF, fibronectin, collagen type IV and VI, while treatment with fluprostenol alone had no effects. The effects of CTGF were blocked by 1-h pretreatment with fluprostenol in a dose-dependent manner. Treatment with fluprostenol or combined fluprostenol/CTGF induced the activity of matrix metalloproteinase 2 (MMP2) in TM cells, whereas treatment with CTGF alone had no effects on MMP2 activity. Conclusions: Fluprostenol blocks the fibrotic effects of CTGF on human TM cells and increases the activity of MMP2. Both effects have the distinct potential to attenuate a CTGF-mediated increase in TM extracellular matrix in patients with POAG and any effects on TM outflow resistance that may result from that.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OPEN-ANGLE GLAUCOMA; UVEOSCLERAL OUTFLOW PATHWAY; NORMAL-TENSION GLAUCOMA; AQUEOUS-HUMOR OUTFLOW; INTRAOCULAR-PRESSURE; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; CILIARY MUSCLE; OCULAR HYPERTENSION; CYNOMOLGUS MONKEY; |
| Subjects: | 500 Science > 570 Life sciences |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Nov 2019 14:12 |
| Last Modified: | 19 Nov 2019 14:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10559 |
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