N-acetylserotonin alleviates retinal autophagy via TrkB/Akt/Nrf2 signaling pathway in retinal ischemia-reperfusion injury rats.

Abstract

Introduction: The objective of this study is to investigate the impact of N-acetylserotonin (NAS) on the autophagy of retinal cells in rats with retinal ischemia-reperfusion injury (RIRI), and to explore the mechanisms by which NAS administration can alleviate RIRI through the tropomyosin-related kinase receptor B (TrkB)/protein kinase B (Akt)/nuclear factor erythroid-derived factor 2-related factor (Nrf2) signaling pathway. Methods: Healthy adult male rats were randomly assigned to four groups: sham, RIRI, RIRI+NAS, and RIRI+NAS+ANA-12. RIRI was induced by elevating intraocular pressure, and changes in retinal structure and edema were assessed using H&E staining. The RIRI+NAS and RIRI+NAS+ANA-12 groups received intraperitoneal injections of NAS before and after modeling. The RIRI+NAS+ANA-12 group was also administered ANA-12, a TrkB antagonist. Immunohistochemical staining and Western blot analysis were used to evaluate phosphorylated TrkB (p-TrkB), phosphorylated Akt (p-Akt), Nrf2, sequestosome 1 (P62), and microtubule-associated protein 1 light chain 3 (LC3-Ⅱ) levels in the retinas of each group. Electroretinogram was recorded to detect retinal function in each group of rats 24h after modeling Results: The RIRI+NAS group had a thinner retina and more retinal ganglion cells (RGCs) than RIRI and RIRI+NAS+ANA-12 groups (p < 0.05). Immunohistochemical staining and Western blots results showed that p-TrkB, p-Akt, n-Nrf-2, and P62 levels in RIRI+NAS group were higher compared with those in RIRI and RIRI+NAS+ANA-12 groups (p < 0.05). And lower LC3-Ⅱ levels were observed in RIRI+NAS group compared with that in RIRI and RIRI+NAS+ANA-12 groups (p < 0.05). Electroretinogram recording results showed that 24 h after retinal ischemia-reperfusion, the magnitude of b-wave changes was attenuated in the RIRI+NAS group compared with the RIRI group (p < 0.05). Conclusion: The administration of NAS activates the TrkB/Akt/Nrf2 signaling pathway, reduces autophagy, alleviates retinal edema, promotes the survival of retinal ganglion cells (RGCs), and provides neuroprotection against retinal injury.