Many signaling proteins are required for collection and processing of light inputs in the retina, and mutations in these proteins can lead to a variety of visual disorders. The long-term objective of the proposed research is to understand the role of the transient receptor potential channel TRPM1 in the retina. Expression of TRPM1 in bipolar cells, which are responsible for collecting the output of rods and cones, has recently been demonstrated. The proposed research is designed to test the hypothesis that TRPM1 is involved in bipolar cell signal transduction. The first specific aim is to determine the precise localization of TRPM1 protein in the retina, using immunohistochemistry. The goal of the second and third aims is to determine whether TRPM1 has a role in visual function and bipolar cell signaling. This will be tested in mice with disrupted expression of TRPM1, using electroretinogram recording of live mice as well as whole-cell patch clamp of bipolar cells in retinal slices. Errors in the transmission of information from photoreceptors (rods and cones) to the subsequent parts of the retinal circuitry result in visual disorders such as congenital stationary night blindness. The proposed research will increase our understanding of the mechanisms used by the secondary neurons of the retina to receive and process information from photoreceptors.
| Agosto, Melina A; Anastassov, Ivan A; Wensel, Theodore G (2018) Differential epitope masking reveals synapse-specific complexes of TRPM1. Vis Neurosci 35:E001 |
| Agosto, Melina A; Zhang, Zhixian; He, Feng et al. (2014) Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a protein essential for dim light vision. J Biol Chem 289:27019-33 |
