Background/Aims: Ocular surface health depends on conjunctival epithelial
(HCjE) layer integrity since it protects against pathogenic infiltration and
contributes to tissue hydration maintenance. As the same increases in tear
film hyperosmolarity described in dry eye disease can increase corneal
epithelial transient receptor potential vanilloid type-1 (TRPV1) channel
activity, we evaluated its involvement in mediating an osmoprotective effect
by L-carnitine against such stress. Methods: Using siRNA gene silencing,
Ca2+imaging, planar patch- clamping and relative cell volume measurements, we
determined if the protective effects of this osmolyte stem from its
interaction with TRPV1. Results: TRPV1 activation by capsaicin (CAP) and an
increase in osmolarity to≈450 mOsM both induced increases in Ca2+levels. In
contrast, blocking TRPV1 activation with capsazepine (CPZ) fully reversed this
response. Similarly, L-carnitine (1 mM) also reduced underlying whole-cell
currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume
shrinkage was fully blocked during exposure to L-carnitine. On the other hand,
in TRPV1 gene-silenced cells, this protective effect by L-carnitine was
obviated. Conclusion: The described L-carnitine osmoprotective effect is
elicited through suppression of hypertonic-induced TRPV1 activation leading to
increases in L-carnitine uptake through a described Na+-dependent L-carnitine
transporter