Conclusions
Sarpogrelate-mediated retinal protection involves a transient activation of the MAPK/ERK pathway, although this pathway alone does not account for the full effect of neuroprotection.
Methods
Albino mice were treated intraperitoneally with saline or sarpogrelate, a 5-HT2A antagonist, immediately before light exposure (LE). Following LE, retinas were harvested for a high-throughput phosphorylation microarray to quantify activated phosphorylated proteins in G protein-coupled receptor (GPCR) signaling. To confirm microarray
Purpose
To characterize the mediators of 5-HT2A serotonin receptor-driven retinal neuroprotection.
Results
Sarpogrelate led to an activation of the MAPK/ERK pathway. Temporal analysis further demonstrated a transient activation of ERK1/2, starting with an early inhibition 20 minutes into LE, a maximum activation at 3 hours post LE, and a return to baseline at 7 hours post LE. Inhibition of ERK1/2 with MEKi pretreatment led to attenuation of sarpogrelate-mediated neuroprotection. LE caused significant changes in the expression of genes involved in iron metabolism, oxidative stress, and apoptosis. These changes were prevented by sarpogrelate treatment. Conclusions: Sarpogrelate-mediated retinal protection involves a transient activation of the MAPK/ERK pathway, although this pathway alone does not account for the full effect of neuroprotection.