Hinokitiol Protects RPE cells from Oxidative and Autophagic Dysfunction: Implications for AMD Therapy

Area of Science:

• Ophthalmology
• Cell Biology
• Pharmacology

Background:

• Age-related macular degeneration (AMD) is a primary cause of vision loss in older adults, linked to retinal pigment epithelial (RPE) cell dysfunction.
• Oxidative stress, driven by reactive oxygen species (ROS), significantly contributes to AMD progression, yet mechanisms are not fully understood.
• Autophagy is crucial for retinal homeostasis, but excessive ROS can impair its function, leading to cell death.

Purpose of the Study:

• To investigate the protective effects of hinokitiol against hydrogen peroxide (H₂O₂)-induced oxidative damage in RPE cells.
• To evaluate hinokitiol's impact on cell viability, ROS levels, antioxidant capacity, DNA damage, mitochondrial function, and autophagy.

Main Methods:

• Cell viability was assessed using MTT and crystal violet staining.
• ROS generation was measured using H₂DCFDA and MitoSOX probes.
• Catalase activity, DNA damage (γ-H2AX, comet assay), mitochondrial membrane potential (JC-1), and autophagy markers (Western blotting) were analyzed.

Main Results:

• Hinokitiol significantly improved RPE cell viability and reduced ROS levels by enhancing catalase activity.
• The compound preserved mitochondrial function and mitigated DNA damage induced by H₂O₂.
• Hinokitiol restored impaired autolysosome fusion, maintaining cellular homeostasis.

Conclusions:

• Hinokitiol demonstrates significant protective effects against oxidative stress in RPE cells.
• Its ability to preserve cellular functions and restore autophagy suggests it is a promising therapeutic candidate for AMD.