Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK‐ULK1 signaling

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. MNU could lead to photoreceptor degeneration by inducing cell senescence which presented as increased senescence‐associated β‐galactosidase activity, ROS generation, DNA injury, oxidative stress, upregulation of cyclin p21 or p16, and reduction in Ki67. However, Hyperoside alleviated the senescence phenotype, attenuated photoreceptor senescence, and prevented MNU‐induced photoreceptor degeneration by inhibiting AMPK‐ULK1 signaling.