Probucol attenuates high glucose-induced Müller cell damage through enhancing the Nrf2/p62 signaling pathway

Area of Science:

• Retinal cell biology
• Diabetic retinopathy research
• Pharmacological interventions

Background:

• High glucose conditions induce oxidative stress and damage in retinal Müller cells, contributing to diabetic retinopathy pathogenesis.
• Müller cells play crucial roles in retinal homeostasis and are vulnerable to metabolic dysfunction.

Purpose of the Study:

• To investigate the protective effects of probucol against high glucose-induced damage in human retinal Müller cells.
• To elucidate the underlying molecular mechanisms, particularly the involvement of the Nrf2/p62 signaling pathway.

Main Methods:

• Primary human retinal Müller cells were cultured under high glucose conditions with varying concentrations of probucol.
• Cell viability, mitochondrial membrane potential (MMP), and cell cycle progression were assessed.
• The expression of key proteins in the Nrf2/p62 pathway (Nrf2, p62) and apoptosis-related proteins (Bcl2) was quantified via qPCR and Western blot.

Main Results:

• High glucose exposure impaired Müller cell proliferation, arrested the cell cycle, and increased MMP.
• Probucol treatment significantly attenuated high glucose-induced cellular damage.
• Probucol upregulated the expression of Nrf2, p62, and the anti-apoptotic protein Bcl2, indicating activation of the Nrf2/p62 pathway.

Conclusions:

• Probucol demonstrates a protective effect on Müller cells against high glucose-induced injury.
• The Nrf2/p62 signaling pathway is a key mechanism mediating probucol's protective action.
• Probucol represents a potential therapeutic agent for managing diabetic retinopathy by safeguarding Müller cell function.