Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China.
Biomed Pharmacother. 2020 Jun;126:110050. doi: 10.1016/j.biopha.2020.110050. Epub 2020 Mar 2.
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 müller 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 müller 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-α 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.
光感受器细胞是一级视网膜神经元，直接参与视觉形成。光感受器变性是导致色素性视网膜炎和年龄相关性黄斑变性等视网膜病变导致视力损害的主要原因，目前尚无针对光感受器的靶向治疗方法。石斛夜光丸（SYP）是一种经典的中药配方，在中国临床应用于治疗多种视网膜病变已有很长的历史。然而，SYP 是否对光感受器细胞具有药理学作用尚不清楚。因此，本研究在一个由强光诱导的视网膜变性的小鼠模型中，直接研究了 SYP 对光感受器变性的药理学意义。通过光学相干断层扫描和视网膜电图分别进行非侵入性全视网膜评估，以评估 SYP 对视网膜结构和功能的影响。此外，通过免疫组织化学和实时 PCR 分析评估光感受器细胞凋亡、二级神经元损伤以及视网膜小胶质细胞和 Muller 细胞的反应性变化，这些都是与光感受器变性相关的标志性病理变化。结果表明，SYP 治疗可减轻强光诱导的视网膜结构和功能损伤。此外，SYP 治疗可抑制光感受器细胞凋亡，减轻双极细胞和水平细胞的损伤，并减轻强光暴露视网膜中 Muller 和小胶质细胞的反应性变化。实时 PCR 分析表明，SYP 治疗可部分纠正强光暴露视网膜中促凋亡 c-fos 和 c-jun 以及抗凋亡 bcl-2 的异常表达和促炎 TNF-α。综上所述，本研究首次证明 SYP 治疗可保护视网膜免受强光诱导的光感受器变性以及二级神经元和神经胶质细胞的相关改变。这些发现为更好地支持 SYP 在治疗相关视网膜退行性疾病中的机制指导的临床应用提供了实验证据。
