Bystander effects elicited by single-cell photo-oxidative blue-light stimulation in retinal pigment epithelium cell...

'Bystander effect' refers to the induction of biological effects in cells not directly targeted. The retinal pigment epithelium consists of hexagonal cells, forming a monolayer interconnected by gap junctions (GJs). Oxidative stress initiated in an individual cell by photostimulation (488 nm) triggered changes in reactive oxygen species (ROS), Ca²⁺ and mitochondrial membrane potential (ψ_m). The Ca²⁺ signal was transmitted to neighboring cells slowly and non-uniformly; the ROS signal spread fast and radially. Increased Ca²⁺ levels were associated with a loss in ψ_m. GJ blockers prevented the spreading of the Ca²⁺, but not the ROS-related signal. The GJ-mediated Ca²⁺ wave was associated with cell death by 24 h, requiring endoplasmic reticulum-mitochondria Ca²⁺ transfer. Ensuing cell death was correlated with baseline Ca²⁺ levels, and baseline Ca²⁺ levels were correlated with pigmentation. Hence, local oxidative stress in a donor cell can trigger changes in certain connected recipient cells, a signal that required GJ communication and an ROS-Ca²⁺ dual-hit. Finally, damage apparently occurred in susceptible cells, which correlated with baseline Ca²⁺ levels.