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经睑电刺激对遗传性视网膜变性小鼠视力的保护作用

Preservation of vision by transpalpebral electrical stimulation in mice with inherited retinal degeneration.

作者信息

Gunes Kasim, Chang Karen, Lennikov Anton, Tai Wai Lydia, Chen Julie, ElZaridi Farris, Cho Kin-Sang, Utheim Tor Paaske, Dong Feng Chen

机构信息

Department of Ophthalmology, Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA, United States.

Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Türkiye.

出版信息

Front Cell Dev Biol. 2024 Aug 14;12:1412909. doi: 10.3389/fcell.2024.1412909. eCollection 2024.

DOI:10.3389/fcell.2024.1412909
PMID:39206091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349514/
Abstract

INTRODUCTION

The potential neuroprotective and regenerative properties of electrical stimulation (ES) were studied in rhodopsin knockout mice ( ), a murine model of inherited retinal degeneration. The study focused on assessing the impact of varying ES frequencies on visual functions and photoreceptor cell survival in mice.

METHODS

To elucidate the impact of electrical stimulation on cone survival, mice received either sham or transpalpebral ES using biphasic ramp or rectangular waveforms at 100 µA amplitude, starting at six weeks of age. The treatment duration spanned from one to three weeks. The optimal treatment frequency of ES sessions was determined by applying ES every one, two, or three days in three separate groups of mice. The sham group received daily treatments without the application of ES.

RESULTS

Our study revealed significant improvement of visual function in mice following daily or every-other-day noninvasive transpalpebral ES, as evidenced by electroretinogram and optomotor response-based visual behavior assays. Concurrently, assessment of outer nuclear thickness and immunohistochemistry for the cone photoreceptor cell marker PNA demonstrated pronounced increases in the survival of rods and cones and improvement in the morphology of the inner and outer segments.

DISCUSSION

This study underscores the protective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, providing a foundation for developing targeted therapeutic interventions for retinitis pigmentosa.

摘要

引言

在遗传性视网膜变性的小鼠模型视紫红质基因敲除小鼠中，研究了电刺激（ES）潜在的神经保护和再生特性。该研究重点评估了不同ES频率对视紫红质基因敲除小鼠视觉功能和光感受器细胞存活的影响。

方法

为阐明电刺激对视锥细胞存活的影响，视紫红质基因敲除小鼠从六周龄开始接受假手术或经睑电刺激，使用双相斜坡或矩形波形，幅度为100微安，治疗持续时间为一至三周。通过在三组视紫红质基因敲除小鼠中分别每隔一天、两天或三天施加电刺激来确定电刺激疗程的最佳治疗频率。假手术组每天接受不施加电刺激的治疗。

结果

我们的研究表明，通过视网膜电图和基于视动反应的视觉行为检测证明，在视紫红质基因敲除小鼠中，每日或隔日进行无创经睑电刺激后视觉功能有显著改善。同时，对视锥光感受器细胞标记物PNA的外核厚度评估及免疫组织化学分析表明，视杆细胞和视锥细胞的存活率显著提高，内外节形态有所改善。

讨论

本研究强调了无创电刺激对视紫红质基因敲除诱导的视网膜退行性疾病的保护作用，为开发针对色素性视网膜炎的靶向治疗干预措施奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/f3231d2bee20/fcell-12-1412909-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/e05c9345a371/fcell-12-1412909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/69a0bc3c7321/fcell-12-1412909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/fcd6e0bdba40/fcell-12-1412909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/44cb9ed9d185/fcell-12-1412909-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/92a444413257/fcell-12-1412909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/f3231d2bee20/fcell-12-1412909-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/e05c9345a371/fcell-12-1412909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/69a0bc3c7321/fcell-12-1412909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/fcd6e0bdba40/fcell-12-1412909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/44cb9ed9d185/fcell-12-1412909-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/92a444413257/fcell-12-1412909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11349514/f3231d2bee20/fcell-12-1412909-g006.jpg

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