The Role of α2δ1 in Mediating Extracellular Signaling in Retinal Cells
Voltage sensitive calcium channels (VSCCs) are key components in coordinating extracellular signaling that influence calcium (Ca2+) influx and subsequent downstream signaling in a variety of tissues including bone. Previous work involving inhibition or genetic deletion of VSCCs impaired bone formation and responses to loading. These studies focused on the pore-forming α1 subunit of VSCCs. In addition to α1, VSCC complexes contain auxiliary subunits, including α2δ1, that influence channel function. The role of the α2δ1 subunit of VSCCs are underappreciated in specific types of neuronal tissue, particularly retinal cells. Clinically, the α2δ1 subunit is pharmacologically targeted by gabapentin, blocking the channel to increase synaptic GABA concentration to aid in modulating nociception. Recently, gabapentin treatment has been associated with cases of macular edema. The purpose of our study was to characterize in vitro models of retinal α2δ1 expression and examine if changes in intraocular pressure are mediated via VSCCs. Two immortalized rat retinal cell lines, R28 and RMC-1, were characterized for α2δ1/4 expression under both static and oscillatory fluid shear stress (OFSS) conditions. Initial Western blot data support that both R28 and RMC-1s are responsive to OFSS as quantified by the phosphorylation of ERK. Ongoing studies are focused on further characterization of the R28 and RMC-1 cells lines for changes in α2δ1/4 expression under static and OFSS conditions. Future studies will include treating R28 and RMC-1 cells with gabapentin to examine its capability of modulating α2δ1 function in retinal cells.
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"The Role of α2δ1 in Mediating Extracellular Signaling in Retinal Cells" (2018). MU-COM Research Day. 106.