Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells

The British Journal of Ophthalmology
B QuillC J O'Brien

Abstract

This study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells. Changes in LC cell intracellular calcium [Ca(2+)]i following hypotonic cell membrane stretch were measured with the fluorescent probe fura-2/AM. Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-β 1 (TGF-β1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR. Hypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p<0.05). Exposure to cyclical mechanical strain (15% strain) produced a statistically significant increase in the three matrix genes that were examined (TGF-β1, COL6A3 and CSPG2). This response in both cyclical and mechanical stretch was significantly reduced by pretreating LC cells with the L-type calcium channel blocker verapamil (p<0.05). This study provides evidence...Continue Reading

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Citations

Jan 13, 2018·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Najam A Sharif
Jun 30, 2019·Alzheimer's Research & Therapy·Cristina M Pedrero-PrietoJuan R Peinado
Jun 19, 2019·Investigative Ophthalmology & Visual Science·Daniel C TurnerJ Crawford Downs
Aug 24, 2019·Cells·Tzyy-Yue WongPei-Wen Cheng

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