Ultrastructural localization and expression of TRPM1 in the human retina

Transient receptor potential subfamily melastatin (TRPM)1 cation channels of retinal ON-bipolar cells are modulated via a mGluR6 (GMR6) signaling cascade. While light-microscopy shows these channels are located on the tips of ON-bipolar cells dendrites, near rod and cone synaptic ribbons, TRPM1 localization at the electron-microscope level is currently not described. The authors report here the ultrastructural localization of TRPM1 in the human retina. TRPM1 was localized in postmortem human retinas by immunohistochemistry at both the light and electron microscope levels. Additionally, TRPM1 expression was studied using in situ hybridization, laser dissection microscopy, and PCR techniques. TRPM1-immunoreactivity was located on the dendrites and soma of ON-bipolar cells at the light microscope level. At the electron microscope level TRPM1-immunoreactivity was located on the tips of ON-bipolar cell dendrites that were invaginating cone pedicles and rod spherules. In addition, TRPM1-immunoreactivity was occasionally found on the rod spherules ribbons, suggesting that at least a proportion of rods may also express TRPM1. In situ hybridization showed TRPM1 encoding RNA in inner nuclear layer somata and in some photoreceptors. The presence of TRPM1-RNA in photoreceptors was confirmed by PCR in pure photoreceptor material obtained with a laser dissection microscope. In the human retina TRPM1 is expressed on ON-bipolar cell dendrites that invaginate photoreceptor terminals. TRPM1 is also expressed on the synaptic ribbons of a subclass of rods, suggesting a dual function for TRPM1 in the ON-pathway