ArticleInvestigative ophthalmology & visual science2016
(+)-Pentazocine Reduces NMDA-Induced Murine Retinal Ganglion Cell Death Through a σR1-Dependent Mechanism.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- 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
- Activation of Sigma 1 Receptor Preserves Visual Function After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- The Neuroprotective Effect of Activation of Sigma-1 Receptor on Neural Injury by Optic Nerve Crush.Investigative ophthalmology & visual science · 2023Article
- Sigma-1 Receptor Agonist Fluvoxamine Ameliorates Fibrotic Response of Trabecular Meshwork Cells.International journal of molecular sciences · 2023Article
- Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells.Life (Basel, Switzerland) · 2023Article
- Article
- Sigma-1 receptor agonist, (+)-pentazocine, is neuroprotective in a Brown Norway rat microbead model of glaucoma.Experimental eye research · 2023Article
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2022Review
- Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection.Investigative ophthalmology & visual science · 2022Article
- Visual Disfunction due to the Selective Effect of Glutamate Agonists on Retinal Cells.International journal of molecular sciences · 2021Article
- Sigma 1 Receptor Modulates Optic Nerve Head Astrocyte Reactivity.Investigative ophthalmology & visual science · 2021Article
- Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury.Frontiers in cellular neuroscience · 2021Review
- Deleterious Effect of NMDA Plus Kainate on the Inner Retinal Cells and Ganglion Cell Projection of the Mouse.International journal of molecular sciences · 2020Article
- Activation of Sigma 1 Receptor Extends Survival of Cones and Improves Visual Acuity in a Murine Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2019Article
- Hyperhomocysteinemia-induced death of retinal ganglion cells: The role of Müller glial cells and NRF2.Redox biology · 2019Article
- The Susceptibility of Retinal Ganglion Cells to Glutamatergic Excitotoxicity Is Type-Specific.Frontiers in neuroscience · 2019Article
- Neuroprotective effect of a dietary supplement against glutamate-induced excitotoxicity in retina.International journal of ophthalmology · 2019Article
Corrections and comments
- Erratum issuedErratum.2016
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo evaluate, in vivo, the effects of the sigma-1 receptor (σR1) agonist, (+)-pentazocine, on N-methyl-D-aspartate (NMDA)-mediated retinal excitotoxicity.
methodsIntravitreal NMDA injections were performed in C57BL/6J mice (wild type [WT]) and σR1-/- (σR1 knockout [KO]) mice. Fellow eyes were injected with phosphate-buffered saline (PBS). An experimental cohort of WT and σR1 KO mice was administered (+)-pentazocine by intraperitoneal injection, and untreated animals served as controls. Retinas derived from mice were flat-mounted and labeled for retinal ganglion cells (RGCs). The number of RGCs was compared between NMDA and PBS-injected eyes for all groups. Apoptosis was assessed using TUNEL assay. Levels of extracellular-signal-regulated kinases (ERK1/2) were analyzed by Western blot.
resultsN-methyl-D-aspartate induced a significant increase in TUNEL-positive nuclei and a dose-dependent loss of RGCs. Mice deficient in σR1 showed greater RGC loss (≈80%) than WT animals (≈50%). (+)-Pentazocine treatment promoted neuronal survival, and this effect was prevented by deletion of σR1. (+)-Pentazocine treatment resulted in enhanced activation of ERK at the 6-hour time point following NMDA injection. The (+)-pentazocine-induced ERK activation was diminished in σR1 KO mice.
conclusionsTargeting σR1 activation prevented RGC death while enhancing activation of the mitogen-activated protein kinase (MAPK), ERK1/2. Sigma-1 receptor is a promising therapeutic target for retinal neurodegenerative diseases.
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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.