ArticleMolecular vision2011
Accelerated retinal ganglion cell death in mice deficient in the Sigma-1 receptor.
Article in Molecular vision, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Prospects for Neuroprotective Therapies in Glaucoma: Drug Targets and Emerging Clinical Strategies.Drug design, development and therapy · 2026Review
- Novel 1-(2-Aryl-2-adamantyl)piperazine Derivatives Exhibit In Vitro Anticancer Activity Across Various Human Cancer Cell Lines, with Selective Efficacy Against Melanoma.Medicina (Kaunas, Lithuania) · 2025Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.Cellular and molecular neurobiology · 2022Review
- Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?Antioxidants (Basel, Switzerland) · 2022Review
- The molecular role of Sigmar1 in regulating mitochondrial function through mitochondrial localization in cardiomyocytes.Mitochondrion · 2022Article
- Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma.Scientific reports · 2021Article
- Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases.Molecular neurobiology · 2021Review
- Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma.Investigative ophthalmology & visual science · 2021Article
- Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.Frontiers in physiology · 2021Review
- The ALS-related σ1R E102Q Mutant Eludes Ligand Control and Exhibits Anomalous Response to Calcium.International journal of molecular sciences · 2020Article
- Article
- Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor.Neurobiology of disease · 2019Article
- The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2.Free radical biology & medicine · 2019Article
- Mutational Analysis of Sigma-1 Receptor's Role in Synaptic Stability.Frontiers in neuroscience · 2019Article
- Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- New Advances in General Biomedical Applications of PAMAM Dendrimers.Molecules (Basel, Switzerland) · 2018Review
- Sigma 1 receptor: A novel therapeutic target in retinal disease.Progress in retinal and eye research · 2018Review
- Cardiac Dysfunction in the Sigma 1 Receptor Knockout Mouse Associated With Impaired Mitochondrial Dynamics and Bioenergetics.Journal of the American Heart Association · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe sigma-1 receptor (σR1), a ligand-operated chaperone, has been inferred to be neuroprotective in previous studies using σR1 ligands. The σR1 specificity of the protective function, however, has yet to be firmly established, due to the existence of non-σR1 targets of the ligands. Here, we used the σR1-knockout mouse (Sigmar1(-/-)) to demonstrate unambiguously the role of the σR1 in protecting the retinal ganglion cells against degeneration after acute damage to the optic nerve.
methodsRetinal σR binding sites were labeled with radioiodinated σR ligands and analyzed by autoradiography. Localization of the σR1 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.
resultsPhotoaffinity labeling indicated the presence of the σR1 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.
conclusionsOur 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 σR1 in alleviating retinal degeneration. This conclusion is consistent with the previous pharmacological studies using σR1 agonists. Thus, our study supports the idea that the σR1 is a promising therapeutic target for neurodegenerative retinal diseases, such as glaucoma.
Indexed as
Identifiers
21541278PMC3084245W1523681909What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.