Shihu Yeguang Pill protects against bright light-induced photoreceptor degeneration in part through suppressing photoreceptor apoptosis
Shihu Yeguang Pill protects against bright light-induced photoreceptor degeneration in part through suppressing photoreceptor apoptosis
复制标题
石虎夜光丸部分通过抑制光感受器凋亡来防止强光诱导的光感受器变性
DOI：
10.1016/j.biopha.2020.110050
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发表时间：
2020-06-01
影响因子：
7.5
通讯作者：
Chen, Yu
中科院分区：
文献类型：
--
作者：
Wu, Hanhan;Xu, Jing;Chen, Yu
感光细胞是一级视网膜神经元，直接参与视觉的形成。光感受器变性是视网膜病变过程中视力损害的主要原因，如视网膜色素变性和年龄相关性黄斑变性，目前尚无光感受器靶向治疗方法。石虎夜光丸（SYP）是中药经典配方，在中国具有悠久的临床应用历史，治疗多种视网膜病变。然而，SYP是否具有保护感光细胞的药理作用尚不清楚。因此，目前的研究直接解决了SYP在以明亮光线诱导的视网膜变性为特征的小鼠模型中的光感受器变性的药理意义。通过光学相干断层扫描和视网膜电图进行无创全视网膜评估，分别评估SYP对视网膜结构和功能的影响。此外，利用免疫组织化学和实时PCR分析评估光感受器凋亡、视网膜小胶质细胞和穆勒细胞的二级神经元损伤和反应性改变，以及与光感受器变性相关的标志性病理。结果表明，SYP治疗可减轻强光引起的视网膜结构和功能损伤。此外，SYP处理可抑制光感受器凋亡，减轻双极细胞和水平细胞的损伤，减轻muller细胞和小胶质细胞的反应性变化。Real-time PCR分析显示，SYP治疗后，促凋亡的c-fos和c-jun、抗凋亡的bcl-2以及促炎的tnf - α的表达异常部分正常化。总之，这项研究首次证明了SYP治疗可以保护视网膜免受强光诱导的光感受器变性和二级神经元和神经胶质细胞的相关改变。本研究结果为SYP治疗相关视网膜退行性疾病的机制指导临床应用提供了实验依据。
Photoreceptor cells are first-order retinal neurons that directly contribute to the formation of vision. Photoreceptor degeneration is the primary cause of vision impairment during the course of retinopathies such as retinitis pigmentosa and age-related macular degeneration, for which photoreceptor-targeted therapies are currently unavailable. Shihu Yeguang Pill (SYP), a classic formula in traditional Chinese medicine, has a long histology of clinical application for the treatment of a wide range of retinopathies in China. However, whether SYP is pharmacological effective at protecting photoreceptor cells is unclear. The current study thus directly addressed the pharmacological implications of SYP in photoreceptor degeneration in a mouse model characterized by bright light-induced retinal degeneration. Non-invasive full-retinal assessment was carried out to evaluate the effect of SYP on the retinal structure and function through optical coherence tomography and electroretinography, respectively. In addition, photoreceptor apoptosis, second-order neuron impairment and reactive changes in retinal microglial and muller cells, hallmark pathologies associated with photoreceptor degeneration, were assessed using immunohistochemistry and real-time PCR analyses. The results showed that SYP treatment attenuated bright light-induced impairment of the retinal structure and function. Moreover, SYP treatment suppressed photoreceptor apoptosis, alleviated the impairment of bipolar and horizontal cells and mitigated the reactive changes of muller and microglial cells in the bright light-exposed retinas. Real-time PCR analyses showed that dysregulated expression of pro-apoptotic c-fos and c-jun and anti-apoptotic bcl-2 as well as proinflammatory TNF-alpha in the bright light-exposed retinas was partially normalized as a result of SYP treatment. In summary, the work here demonstrates for the first time that SYP treatment protects the retinas from developing bright light-induced photoreceptor degeneration and associated alterations in second-order neurons and glial cells. The findings here thus provide experimental evidence to better support the mechanism-guided clinical application of SYP in the treatment of related retinal degenerative diseases.