N-Acetylserotonin Alleviates Retinal Autophagy via TrkB/AKT/Nrf2 Signaling Pathway in Retinal Ischemia-Reperfusion...

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Retinal ischemia-reperfusion injury (RIRI) is a significant cause of vision loss.
• Autophagy plays a complex role in RIRI, with excessive autophagy contributing to cell death.
• N-acetylserotonin (NAS) has shown neuroprotective potential in various conditions.

Purpose of the Study:

• To investigate the protective effects of NAS on retinal cells in a rat model of RIRI.
• To elucidate the underlying molecular mechanisms, focusing on the TrkB/Akt/Nrf2 signaling pathway and autophagy.
• To determine if NAS can alleviate RIRI-induced retinal damage and functional impairment.

Main Methods:

• Rats were subjected to RIRI and treated with NAS or a TrkB antagonist (ANA-12).
• Retinal structure and edema were assessed using H&E staining.
• Protein levels of p-TrkB, p-Akt, Nrf2, P62, and LC3-II were quantified via Western blot and immunohistochemistry.
• Retinal function was evaluated using electroretinography.

Main Results:

• NAS treatment significantly reduced retinal thinning and increased the survival of retinal ganglion cells (RGCs) compared to RIRI controls.
• NAS administration upregulated p-TrkB, p-Akt, and Nrf2, and increased P62 levels.
• NAS treatment decreased LC3-II levels, indicating reduced autophagy.
• Electroretinogram results showed improved retinal function (b-wave magnitude) in the NAS-treated group.

Conclusions:

• NAS activates the TrkB/Akt/Nrf2 signaling pathway in the context of RIRI.
• NAS administration effectively reduces autophagy and alleviates RIRI-induced retinal edema.
• NAS promotes RGC survival and provides significant neuroprotection against retinal injury.