Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina

Sigma receptors are nonopiate and nonphencyclidine binding sites that are t hought to be neuroprotective due to modulation of N-methyl-n-aspartate (NMD A) receptors. Sigma receptor 1 expression has been demonstrated in numerous tissues including brain. Recently, studies using binding assays have demon strated sigma receptor I in neural retina, however these studies did not de monstrate in which retinal cell type(s) sigma receptor 1 was present nor di d they establish unequivocally the molecular identity of the receptor. The present study was designed to address these issues. Reverse transcription-p olymerase chain reaction (RT-PCR) analysis amplified sigma receptor 1 in ne ural retina, RPE-choroid complex, and lens isolated from mice. A similar RT -PCR product was amplified also in three cultured cell lines; rat Muller ce lls, rat ganglion cells and human ARPE-19 cells. In situ hybridization anal ysis revealed abundant sigma receptor 1 expression in ganglion cells, cells of the inner nuclear layer, inner segments of photoreceptor cells and reti nal pigment epithelial (RPE) cells. Immunohistochemical studies detected th e sigma receptor 1 protein in retinal ganglion, photoreceptor, RPE cells an d surrounding the soma of cells in the inner nuclear layer. These data prov ide the first cellular localization of sigma receptor 1 in neural retina an d establish the molecular identity of sigma receptor 1 in retinal cell's. T he demonstration that sigma receptor 1 is present in ganglion cells is part icularly noteworthy given the well-documented susceptibility of these cells to glutamate toxicity. Our findings suggest that retinal ganglion cells ma y be amenable to the neuroprotective effects of sigma ligands under conditi ons of neurotoxicity such as occurs in diabetes. (C) 2001 Elsevier Science B.V. All rights. reserved.