ArticleInvestigative ophthalmology & visual science2017
Absence of Sigma 1 Receptor Accelerates Photoreceptor Cell Death in a Murine Model of Retinitis Pigmentosa.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- 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
- Role of Fibroblast Growth Factor Receptor 2 (FGFR2) in Corneal Stromal Thinning.Investigative ophthalmology & visual science · 2023Article
- Sigma 1 receptor activation improves retinal structure and function in the RhoExperimental eye research · 2023Article
- Article
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma.Scientific reports · 2021Article
- The role of sigma 1 receptor in organization of endoplasmic reticulum signaling microdomains.eLife · 2021Article
- Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases.International journal of molecular sciences · 2021Article
- Optimal timing for activation of sigma 1 receptor in the Pde6bExperimental eye research · 2021Article
- Review
- Comparison of Neuroprotective Effects of Monomethylfumarate to the Sigma 1 Receptor Ligand (+)-Pentazocine in a Murine Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2020Article
- Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice.Journal of clinical medicine · 2020Article
- Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update.Oxidative medicine and cellular longevity · 2020Review
- PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus.Scientific reports · 2019Article
- Effect ofPhysiological genomics · 2019Article
- Delineating the role of eIF2α in retinal degeneration.Cell death & disease · 2019Article
- The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2.Free radical biology & medicine · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: Sigma 1 Receptor (Sig1R) is a novel therapeutic target in neurodegenerative diseases, including retinal disease. Sig1R-/- mice have late-onset retinal degeneration with ganglion cell loss that worsens under stress. Whether Sig1R plays a role in maintaining other retinal neurons is unknown, but was investigated here using rd10 mice, a model of severe photoreceptor degeneration. Methods: Wild-type, rd10, and rd10/Sig1R-/- mice were subjected to ERG and spectral-domain optical coherence tomography (SD-OCT) to assess visual function/structure in situ. Retinas imaged microscopically were subjected to morphometric analysis, immunodetection of cones, and analysis of gliosis. Oxidative and endoplasmic reticulum (ER) stress was evaluated at mRNA/protein levels. Results: Photopic ERG responses were reduced significantly in rd10/Sig1R-/- versus rd10 mice at P28 (31 ± 6 vs. 56 ± 7 μV), indicating accelerated cone loss when Sig1R was absent. At P28, SD-OCT revealed reduced retinal thickness in rd10/Sig1R-/- mice (60% of WT) versus rd10 (80% of WT). Morphometric analysis disclosed profound photoreceptor nuclei loss in rd10/Sig1R-/- versus rd10 mice. rd10/Sig1R-/- mice had 35% and 60% fewer photoreceptors, respectively, at P28 and P35, than rd10. Peanut agglutinin cone labeling decreased significantly; gliosis increased significantly in rd10/Sig1R-/- versus rd10 mice. At P21, NRF2 levels increased in rd10/Sig1R-/- mice versus rd10 and downstream antioxidants increased indicating oxidative stress. At P28, ER stress genes/proteins, especially XBP1, a potent transcriptional activator of the unfolded protein response and CHOP, a proapoptotic transcription factor, increased significantly in rd10/Sig1R-/- mice versus rd10. Conclusions: Photoreceptor cell degeneration accelerates and cone function diminishes much earlier in rd10/Sig1R-/- than rd10 mice emphasizing the importance of Sig1R as a modulator of retinal cell survival.
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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.