Endocrine Abstracts (2017) 49 EP806 | DOI: 10.1530/endoabs.49.EP806

3-Iodothyronamine induces transient receptor potential melastatin 8 (TRPM8) channel activation in human corneal endothelial cells and human corneal keratocytes

Nina Ljubojevic1, Noushafarin Khajavi2, Katharina Lohse1, Monika Valtink3 & Stefan Mergler1

1Klinik für Augenheilkunde – Charité Universitätsmedizin Berlin, Berlin, Germany; 2Institut für Experimentelle Pädiatrische Endokrinologie, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3Institute of Anatomy, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.

3-Iodothyronamine (3-T1AM) is an endogenous metabolite of thyroid hormone (TH) for which was shown to have various effects. One of the effects is body temperature decline, which may be related with menthol receptor TRPM8. Normally, this ion channel is expressed in neuronal tissue, where it has a nociceptive role. Functional TRPM8 expression has also been shown in non-neuronal cells of the eye such as corneal and conjunctival epithelial cells, corneal endothelial cells as well as human corneal keratocytes. Furthermore, we could demonstrate in previous studies that 3-T1AM acts as a cooling agent in human corneal epithelial and conjunctival epithelial cells and that it is suppressing TRPV1 channel (capsaicin receptor), which plays an important role in dry eye disease. Here, we determined in a human corneal endothelial cell line (HCEC-12) and a human corneal keratocyte cell line (HCK) if 3-T1AM also acts as a cooling agent to directly affect TRPM8 at a constant temperature. Functional activity was evaluated by comparing the effects of 3-T1AM with those of TRPM8 known agonists on intracellular Ca2+ currents and whole-cell currents using fluorescent Ca2+-imaging and planar patch-clamping. Menthol (500 μM), a specific TRPM8 activator, evoked a Ca2+ influx as well as an increase of whole-cell currents. This effect could be blocked by BCTC (20 μM) and AMTB (20 μM), both selective TRPM8 antagonists. Notably, comparable effects were observed with 1 μM 3-T1AM. Overall, this study completes our previous studies of human corneal and conjunctival epithelial cells. Interestingly, the effect of 3-T1AM has a similar Ca2+ response pattern and similar whole-cell current pattern in all three layers of the cornea. Therefore, this might represent a general biological phenomenon. Further investigation of 3-T1AM effects on the cornea should be performed in order to better characterize a potential benefit of 3-T1AM on the treatment of dry eye disease.

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