Histochem Cell Biol
Department of Ophthalmology, Campus Virchow-Clinic, Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Published: June 2012
Transient receptor potential vanilloid (TRPV) channels respond to polymodal stresses to induce pain, inflammation and tissue fibrosis. In this study, we probed for their functional expression in human conjunctival epithelial (HCjE) cells and ex vivo human conjunctivas. Notably, patients suffering from dry eye syndrome experience the same type of symptomology induced by TRPV channel activation in other ocular tissues. TRPV gene and protein expression were determined by RT-PCR and immunohistochemistry in HCjE cells and human conjunctivas (body donors). The planar patch-clamp technique was used to record nonselective cation channel currents. Ca(2+) transients were monitored in fura-2 loaded cells. Cultivated HCjE cells and human conjunctiva express TRPV1, TRPV2, and TRPV4 mRNA. TRPV1 and TRPV4 localization was identified in human conjunctiva. Whereas the TRPV1 agonist capsaicin (CAP) (5-20 μM) -induced Ca(2+) transients were blocked by capsazepine (CPZ) (10 μM), the TRPV4 activator 4α-PDD (10 μM) -induced Ca(2+) increases were reduced by ruthenium-red (RuR) (20 μM). Different heating (<40°C or >43°C) led to Ca(2+) increases, which were also reduced by RuR. Hypotonic challenges of either 25 or 50% induced Ca(2+) transients and nonselective cation channel currents. In conclusion, conjunctiva express TRPV1, TRPV2, and TRPV4 channels which may provide novel drug targets for dry eye therapeutics. Their usage may have fewer side effects than those currently encountered with less selective drugs.
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http://dx.doi.org/10.1007/s00418-012-0924-5 | DOI Listing |
JCI Insight
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The Wistar Institute, Philadelphia, Pennsylvania, USA.
Vaccines (Basel)
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View Article and Find Full Text PDFJ Pharm Pharmacol Res
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McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Purpose: Environmentally-triggered dry eye disease (DED) or keratoconjunctivitis sicca (KCS), which constitutes the majority of DED cases, currently is palliatively treated with aqueous replacement solutions that do not target the dysfunction of the mucin and lipid components of tears. We tested whether a peptide that increased goblet cell numbers in a model of scleral chemical injury would also improve tear quality in environmental DED.
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J Clin Med
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Department of Ophthalmology, University Hospital, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany.
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View Article and Find Full Text PDFCornea
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Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, School of Medicine, Birmingham, AL.
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