| First Author | Mavlyutov TA | Year | 2011 |
| Journal | Mol Vis | Volume | 17 |
| Pages | 1034-43 | PubMed ID | 21541278 |
| Mgi Jnum | J:179534 | Mgi Id | MGI:5302616 |
| Citation | Mavlyutov TA, et al. (2011) Accelerated retinal ganglion cell death in mice deficient in the Sigma-1 receptor. Mol Vis 17:1034-43 |
| abstractText | PURPOSE: The sigma-1 receptor (sigmaR1), a ligand-operated chaperone, has been inferred to be neuroprotective in previous studies using sigmaR1 ligands. The sigmaR1 specificity of the protective function, however, has yet to be firmly established, due to the existence of non-sigmaR1 targets of the ligands. Here, we used the sigmaR1-knockout mouse (Sigmar1(-/-)) to demonstrate unambiguously the role of the sigmaR1 in protecting the retinal ganglion cells against degeneration after acute damage to the optic nerve. METHODS: Retinal sigmaR binding sites were labeled with radioiodinated sigmaR ligands and analyzed by autoradiography. Localization of the sigmaR1 was performed by indirect immunofluorescence on frozen retinal sections. Retinal ganglion cell death was induced by acute optic nerve crush in wild-type and Sigmar1(-/-) mice. Surviving cells in the ganglion cell layer were counted on Nissl-stained retinal whole mounts 7 days after the crush surgery. RESULTS: Photoaffinity labeling indicated the presence of the sigmaR1 in the retina, in concentrations equivalent to those in liver tissue. Immunolabeling detected this receptor in cells of both the ganglion cell layer and the photoreceptor cell layer in wild-type retinas. Quantification of cells remaining after optic nerve crush showed that 86.8+/-7.9% cells remained in the wild-type ganglion cell layer, but only 68.3+/-3.4% survived in the Sigmar1(-/-), demonstrating a significant difference between the wild-type and the Sigmar1(-/-) in crush-induced ganglion cell loss. CONCLUSIONS: Our data indicated faster retinal ganglion cell death in Sigmar1(-/-) than in wild-type mice under the stresses caused by optic nerve crush, providing direct evidence for a role of the sigmaR1 in alleviating retinal degeneration. This conclusion is consistent with the previous pharmacological studies using sigmaR1 agonists. Thus, our study supports the idea that the sigmaR1 is a promising therapeutic target for neurodegenerative retinal diseases, such as glaucoma. |
