Inhibiting the activation of MAPK (ERK1/2) in stressed Müller cells prevents photoreceptor degeneration

MAPK (ERK1/2) signalling was exclusively activated in Müller cells under stress, both ex vivo and in vivo. PD98059, a specific pERK1/2 inhibitor, inhibited the phosphorylation of ERK1/2 in Müller cells, reduced the gliotic marker glial fibrillary acidic protein (GFAP) and increased neuroprotective factor interphotoreceptor retinoid-binding protein (IRBP). Inhibition of pERK1/2 reduced retinal injury in photo-oxidative damaged mice assessed by optical coherence tomography (OCT). However, exactly how Müller cells and photoreceptors communicate under stress, as well as the signalling pathways involved, remains unclear. We explored the RNA and signalling pathway changes after MAPK deactivation in human retina explants by RNA sequence. 8 mRNA profiles of human retina explants cultured from 4 donors, including 2 groups with different treatments (DMSO and ERK1/2 inhibitor treatment)