Fig. 5

Upper eyelid is densely innervated by TRPM8 fibers and is the target of drug delivery. (a) TRPM8-expressing sensory fibers (green) densely innervate the skin of upper eyelid as revealed by the whole-mount staining of TRPM8-GFP fromTrpm8 ^EGFPf/+transgenic mice. White arrows indicate Trpm8 ^EGFPf/+fiber axons and terminals. (b) Trigeminal ganglion neurons which innervate the upper eyelid are revealed by microinjection of neuronal retrograde tracer, Fluoro-Gold™, in the upper eyelid. White arrows indicate TRPM8⁺/fluorogold⁺ neurons. Scale bars in (a): 250 μm, (b): 100 μm. (c) The method to topically apply test solutions to target TRPM8 on the eyelid margins