Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, Shenzhen, Guangdong, China.
FASEB J. 2023 Nov;37(11):e23250. doi: 10.1096/fj.202301273RR.
Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated β-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.
视力丧失和失明通常是由光感受器变性引起的，例如年龄相关性黄斑变性和色素性视网膜炎。然而，目前尚无有效的药物来治疗这些与光感受器变性相关的疾病。细胞衰老在许多疾病中是一种常见的表型；然而，很少有研究报道它是否发生在光感受器变性疾病中。在此，我们发现细胞衰老与 N-甲基-N-亚硝基脲（MNU，一种常用的光感受器变性模型）诱导的光感受器变性有关，表现为衰老相关β-半乳糖苷酶活性、DNA 损伤、氧化应激和炎症相关细胞因子白细胞介素 6（IL6）增加，以及细胞周期蛋白 p21 或 p16 上调。这些结果表明，使用抗衰老治疗可能会保护视觉功能。此外，淫羊藿苷被报道有助于预防各种器官的衰老。在这项研究中，我们表明玻璃体内递送达马酮苷可减轻光感受器细胞衰老，并改善体内和体外视网膜的功能和形态变性。重要的是，达马酮苷通过抑制 AMPK-ULK1 信号通路来减轻 MNU 诱导的光感受器损伤和衰老。总之，我们的结果表明，淫羊藿苷可以通过 AMPK-ULK1 通路抑制细胞衰老来预防 MNU 诱导的光感受器变性。
