Academic Journal

Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma

التفاصيل البيبلوغرافية
العنوان: Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma
المؤلفون: Li, Linya, He, Shaoqing, Liu, Yang, Yorio, Thomas, Ellis, Dorette Z.
المصدر: Investigative Ophthalmology & Visual Science
بيانات النشر: ARVO Journals
سنة النشر: 2022
المجموعة: UNTHSC Scholarly Repository (University. of North Texas Health Science Center)
مصطلحات موضوعية: Animals, Apoptosis, Disease Models, Animal, Electroretinography, Glaucoma / complications, Glaucoma / genetics, Glaucoma / pathology, Mice, Inbred C57BL, Knockout, Nerve Crush / methods, Optic Nerve Injuries / etiology, Optic Nerve Injuries / genetics, Optic Nerve Injuries / pathology, Receptors, sigma / biosynthesis, sigma / genetics, Retinal Ganglion Cells / metabolism, Retinal Ganglion Cells / pathology, Signal Transduction
الوصف: Purpose: The purpose of this study was to determine the effects of the Sigma-1R (sigma-1r) on retinal ganglion cell (RGC) survival following optic nerve crush (ONC) and the signaling mechanism involved in the sigma-1r protection. Methods: The overall strategy was to induce injury by ONC and mitigate RGC death by increasing sigma-1r expression and/or activate sigma-1r activity in sigma-1r K/O mice and wild type (WT) mice. AAV2-sigma-1r vector was used to increase sigma-1r expression and sigma-1r agonist used to activate the sigma-1r and RGCs were counted. Immunohistochemical and Western blot analysis determined phosphorylated (p)-c-Jun, c-Jun, and Caspase-3. Pattern electroretinography (PERG) determined RGC activity. Results: RGC counts and function were similar in pentazocine-treated WT mice when compared to untreated mice and in WT mice when compared with sigma-1r K/O mice. Pentazocine-induced effects and the effects of sigma-1r K/O were only observable after ONC. ONC resulted in decreased RGC counts and activity in both WT and sigma-1r K/O mice, with sigma-1r K/O mice experiencing significant decreases compared with WT mice. The sigma-1r transgenic expression resulted in increased RGC counts and activity following ONC. In WT mice, treatment with sigma-1r agonist pentazocine resulted in increased RGC counts and increased activity when compared with untreated WT mice. There were time-dependent increases in c-jun, p-c-jun, and caspase-3 expression in ONC mice that were mitigated with pentazocine-treatment. Conclusions: These findings suggest that the apoptotic pathway is involved in RGC losses seen in an ONC model. The sigma-1r offers neuroprotection, as activation and/or transgenic expression of sigma-1r attenuated the apoptotic pathway and restored RGCs number and function following ONC. ; Supported by University of North Texas Systems College of Pharmacy.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: unknown
تدمد: 1552-5783
Relation: https://doi.org/10.1167/iovs.62.10.17; Li, L., He, S., Liu, Y., Yorio, T., & Ellis, D. Z. (2021). Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma. Investigative ophthalmology & visual science, 62(10), 17. https://doi.org/10.1167/iovs.62.10.17; https://hdl.handle.net/20.500.12503/31757; 62; 10
الاتاحة: https://hdl.handle.net/20.500.12503/31757
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; Copyright 2021 The Authors
رقم الانضمام: edsbas.DD0DD255
قاعدة البيانات: BASE