ArticleProceedings of the National Academy of Sciences of the United States of America2016
Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Sigma1 Receptor Activation Confers Durable Neuroprotection Following Neonatal Ischemic Retinal Injury.Research square · 2026Article
- Sigma 1 Receptor Activation Coordinates Metabolic Stress Responses to Protect Retinal Vasculature in Ischemic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- Reactive Oxygen Species Regulation Across Retinitis Pigmentosa Animal Models: A 25-Year Systematized Review.Molecular neurobiology · 2025Review
- Activation of Sigma 1 Receptor Preserves Visual Function After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Intrinsic signal optoretinography of dark adaptation abnormality due to rod photoreceptor degeneration.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Evaluation of the role of Sigma 1 receptor and Cullin3 in retinal photoreceptor cells.Free radical biology & medicine · 2023Article
- Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells.Life (Basel, Switzerland) · 2023Article
- Sigma-1 Receptor Agonist Fluvoxamine Ameliorates Fibrotic Response of Trabecular Meshwork Cells.International journal of molecular sciences · 2023Article
- Sigma 1 receptor activation improves retinal structure and function in the RhoExperimental eye research · 2023Article
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- Nucleoporin POM121 signals TFEB-mediated autophagy via activation of SIGMAR1/sigma-1 receptor chaperone by pridopidine.Autophagy · 2023Article
- Defining the ligand-dependent proximatome of the sigma 1 receptor.Frontiers in cell and developmental biology · 2023Article
- Sigma-1 receptor agonist, (+)-pentazocine, is neuroprotective in a Brown Norway rat microbead model of glaucoma.Experimental eye research · 2023Article
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- Differential Responses to Sigma-1 or Sigma-2 Receptor Ablation in Adiposity, Fat Oxidation, and Sexual Dimorphism.International journal of molecular sciences · 2022Article
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- Generation of Sigmar1 conditional knockout mouse using CRISPR-Cas9 gene targeting.Genesis (New York, N.Y. : 2000) · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Retinal degenerative diseases are major causes of untreatable blindness, and novel approaches to treatment are being sought actively. Here we explored the activation of a unique protein, sigma 1 receptor (Sig1R), in the treatment of PRC loss because of its multifaceted role in cellular survival. We used Pde6β(rd10) (rd10) mice, which harbor a mutation in the rod-specific phosphodiesterase gene Pde6β and lose rod and cone photoreceptor cells (PRC) within the first 6 wk of life, as a model for severe retinal degeneration. Systemic administration of the high-affinity Sig1R ligand (+)-pentazocine [(+)-PTZ] to rd10 mice over several weeks led to the rescue of cone function as indicated by electroretinographic recordings using natural noise stimuli and preservation of cone cells upon spectral domain optical coherence tomography and retinal histological examination. The protective effect appears to result from the activation of Sig1R, because rd10/Sig1R(-/-) mice administered (+)-PTZ exhibited no cone preservation. (+)-PTZ treatment was associated with several beneficial cellular phenomena including attenuated reactive gliosis, reduced microglial activation, and decreased oxidative stress in mutant retinas. To our knowledge, this is the first report that activation of Sig1R attenuates inherited PRC loss. The findings may have far-reaching therapeutic implications for retinal neurodegenerative diseases.
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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.