Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
Psalmotoxin-1, a novel TRPM2 channel antagonist, reduces age-related macular degeneration-caused mitochondrial oxidative damage and apoptosis in human retinal pigment epithelial (ARPE-19) cells.
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Özkaya Dilek, Nazıroğlu Mustafa
Аннотация
PURPOSE: Age-related macular degeneration (AMD) develops as a result of mitochondrial reactive oxygen species (mitROS) and apoptosis caused by increased Ca2+ influx via the overstimulation of transient receptor potential melastatin 2 (TRPM2). Psalmotoxin-1 (PSTX) has acid-sensing ion channel (ASIC) inhibitor and antioxidant actions in several cells. PSTX has been shown to modulate hypoxia-induced oxidative cytotoxicity and cell death in mouse eye cells by inhibiting ASIC-mediated Ca2+ influx; however, this mechanism does not apply to AMD. In this study, we investigated how PSTX inhibits TRPM2 to protect human retinal pigment epithelium - 19 (ARPE-19) cells against mitROS damage and apoptosis caused by sodium iodate (SoI).
MATERIALS AND METHODS: Control (CONT), 20 nM PSTX for 24 h, 10 mM SoI for 24 h, SoI + PSTX, and SoI + TRPM2 antagonist (25 µM N-(p-amylcinnamoyl) anthranilic acid, ACA) groups were induced in the ARPE-19 cells.
RESULTS: The ADP-ribose-induced TRPM2 current density, Fe2+, and H2O2-induced cytosolic Ca2+ concentrations were elevated by the SoI treatment. Additionally, its treatment increased the markers of apoptosis, caspases (caspase-3, -8, and - 9), oxidative stress, and mitochondrial membrane dysfunction while lowering glutathione (GSH), glutathione peroxidase (GSH-Px), and cell viability number. GSH, GSH-Px, and cell viability were enhanced, whereas oxidative stress and cell death indicators were decreased via TRPM2 inhibition by the treatments of PSTX and ACA.
CONCLUSION: The results of the preliminary study indicated that PSTX incubation blocked TRPM2-mediated Ca2+ signaling, reducing AMD-induced mitochondrial oxidant injury and cell death. PSTX, a new TRPM2 antagonist, may be utilized to treat oxidative stress and aberrant Ca2+ influx induced by AMD.
MATERIALS AND METHODS: Control (CONT), 20 nM PSTX for 24 h, 10 mM SoI for 24 h, SoI + PSTX, and SoI + TRPM2 antagonist (25 µM N-(p-amylcinnamoyl) anthranilic acid, ACA) groups were induced in the ARPE-19 cells.
RESULTS: The ADP-ribose-induced TRPM2 current density, Fe2+, and H2O2-induced cytosolic Ca2+ concentrations were elevated by the SoI treatment. Additionally, its treatment increased the markers of apoptosis, caspases (caspase-3, -8, and - 9), oxidative stress, and mitochondrial membrane dysfunction while lowering glutathione (GSH), glutathione peroxidase (GSH-Px), and cell viability number. GSH, GSH-Px, and cell viability were enhanced, whereas oxidative stress and cell death indicators were decreased via TRPM2 inhibition by the treatments of PSTX and ACA.
CONCLUSION: The results of the preliminary study indicated that PSTX incubation blocked TRPM2-mediated Ca2+ signaling, reducing AMD-induced mitochondrial oxidant injury and cell death. PSTX, a new TRPM2 antagonist, may be utilized to treat oxidative stress and aberrant Ca2+ influx induced by AMD.