Crocin Protects Against Retinal Ischemia-Reperfusion Injury via Regulating Sirt6-Mediated Nrf2/HO-1 Pathway in Rats

Area of Science:

• Ophthalmology
• Neuroscience
• Pharmacology

Background:

• Retinal ischemia-reperfusion (RIR) injury causes significant damage to retinal ganglion cells (RGCs).
• Current treatments for RIR injury are limited, highlighting the need for novel therapeutic agents.
• Understanding the molecular mechanisms underlying RIR injury is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the protective effects of crocin against RIR injury in RGCs.
• To elucidate the role of the Sirt6-mediated Nrf2/HO-1 signaling pathway in crocin's protective mechanism.

Main Methods:

• Primary RGCs and rat models of RIR injury were used.
• Cells and animals were treated with varying doses of crocin.
• Cell viability, apoptosis, endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and inflammatory markers were assessed.
• Western blotting and qRT-PCR were employed to analyze protein and gene expression.
• Sirt6 and Nrf2 were silenced using siRNA, and an Nrf2 inhibitor (ML385) was used in vivo.

Main Results:

• Crocin significantly enhanced RGC viability and reduced apoptosis following RIR injury.
• Crocin treatment attenuated ROS accumulation, ERS, and pro-inflammatory cytokine expression.
• Crocin upregulated Sirt6, promoted Nrf2 nuclear translocation, and increased HO-1 levels, activating the Sirt6-Nrf2/HO-1 pathway.
• Silencing Sirt6 or Nrf2, or inhibiting Nrf2 in vivo, abolished crocin's protective effects.

Conclusions:

• Crocin confers protection to RGCs against RIR injury via the Sirt6-Nrf2/HO-1 pathway.
• Crocin alleviates RGCs from ERS, inflammation, apoptosis, and oxidative stress.
• Crocin demonstrates potential as a therapeutic agent for retinal ischemic diseases.