Wu Hanhan, Zhu Beijing, Li Daijin, Xu Jing, Chang Jie, Du Xiaoye, Cui Jingang, Zhang Ning, Zhang Teng, Chen Yu
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2022 Jun 8;13:904849. doi: 10.3389/fphar.2022.904849. eCollection 2022.
Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases.
蓝靛果(CCL)是一种在传统中药中广泛用于治疗眼科疾病的草药,包括与年龄相关的威胁视力的视网膜退行性疾病,这些疾病涉及一级视网膜神经元即光感受器的不可逆丧失。然而,关于CCL在保护光感受器免受损失以及与光感受器退化相关视网膜结构和功能损伤方面是否具有药理活性,目前尚缺乏证据。因此,本研究评估了CCL潜在的光感受器保护作用,以更好地支持其在预防和治疗光感受器退行性疾病中的临床应用。采用非侵入性全视网膜光学相干断层扫描、视网膜电图、组织学检查、免疫组织化学和实时定量聚合酶链反应分析,评估CCL对光暴露BALB/c小鼠的视网膜保护作用,这些小鼠表现为光氧化应激介导的光感受器丧失以及相关的视网膜形态和功能损伤。结果表明,CCL治疗可防止光诱导的光感受器结构退化和视网膜功能恶化。此外,CCL治疗增加了视紫红质、S-视蛋白和M-视蛋白在视网膜中的表达,支持了CCL对视杆和视锥光感受器的保护作用。CCL治疗抑制了光暴露视网膜中的光感受器细胞死亡。由于CCL治疗,二级视网膜神经元的形态完整性也得以保留。此外,CCL治疗减轻了光诱导的视网膜反应性穆勒胶质细胞增生、小胶质细胞激活和炎症。总之,目前的研究首次证明CCL可防止光氧化应激介导的光感受器退化以及相关的视网膜结构、功能和免疫稳态紊乱。因此,本研究结果提供了新的实验证据,支持CCL在预防和治疗光感受器退行性疾病中的临床应用。