Purpose: We investigated the possible protective effects of rituximab (RTX) on LPS-induced oxidant, inflammatory, and apoptotic adverse actions via the inhibition of TRPM2 channel in the adult retinal pigment epithelial-19 (ARPE-19) cells.
Methods: In the cultured ARPE-19 cells, we induced five main groups as control, RTX (10 μg/ml), LPS (1 μg/ml), LPS+RTX, and LPS+TRPM2 blockers (ACA or 2/APB).
Results: The levels of apoptosis, cell death, mitochondrial free reactive oxygen radicals (mitROS), cytosolic ROS, lipid peroxidation, caspase -3, caspase -8, caspase -9, ADP-ribose-induced TRPM2 current density, TNF-α, IL-1β, cytosolic free Zn2+, and Ca2+ were increased by LPS, although their levels were diminished by the treatments of RTX and TRPM2 blockers.
Conclusions: The LPS-induced mitROS, inflammatory cytokine, and apoptosis levels were modulated via TRPM2 inhibition in the human retinal epithelial cells by the RTX treatment. The RTX may be considered as a new therapeutic approach to LPS-induced human retinal epithelial cell injury.
Keywords: ARPE-19 cells; Apoptosis; TRPM2 channel; human retina cells; lipopolysaccharide; oxidative stress; rituximab.