Buspirone Enhances Cell Survival and Preserves Structural Integrity during Oxidative Injury to the Retinal Pigment...

Area of Science:

• Ophthalmology
• Neuroscience
• Pharmacology

Background:

• Chronic oxidative stress damages the retinal pigment epithelium (RPE), a key factor in age-related macular degeneration (AMD) progression.
• The RPE's integrity is crucial for photoreceptor health and overall retinal function.

Purpose of the Study:

• To investigate the protective effects of buspirone, a serotonin 1A (5-HT1A) receptor agonist, against oxidative stress in RPE cells.
• To evaluate buspirone's potential therapeutic role in mitigating AMD-related RPE damage.

Main Methods:

• ARPE-19 cells were exposed to paraquat to induce oxidative stress; buspirone's effects on cell viability and junctional integrity were assessed.
• A mouse model with sodium iodate (NaIO₃)-induced oxidative injury was used to evaluate buspirone's in vivo protective effects.
• RT-PCR, WST-1 assays, ZO-1 immunostaining, and spectral-domain optical coherence tomography (SD-OCT) were employed for analysis.

Main Results:

• Buspirone demonstrated dose-dependent protection of ARPE-19 cell viability and preserved RPE junctional integrity under oxidative stress.
• In vivo, buspirone treatment improved photoreceptor survival and preserved RPE structural integrity in the NaIO₃-induced injury model.
• Buspirone upregulated protective genes including Nqo1, Cat, Sqstm1, Gstm1, and Sod2 in the RPE/choroid.

Conclusions:

• Buspirone exhibits significant protective effects against oxidative stress-induced damage in RPE cells and in vivo models.
• Repurposing buspirone, an established anxiety medication, may offer a novel therapeutic strategy for treating or preventing dry AMD.