Minocycline prevents the inflammatory response after retinal detachment, where microglia phenotypes being regulated through A20

Abstract

Retinal detachment (RD) is a severe sight-threatening complication that can be caused by a multitude of retinal diseases. It has been evidenced that minocycline exerts neuroprotective effects by targeting microglia in the pathogenesis of massive ocular lesions including RD, but mechanisms remain elusive. We carried out this research to elucidate the potential mediators that link RD-induced vision loss with microglia reactivity by discussing effects of minocycline on cytokine levels and A20, a negative regulator of inflammation. Minocycline or vehicle was intraperitoneally administrated immediately after RD and continued daily before animals being euthanized. The oxygen glucose deprivation assay was undertaken on the co-cultured BV-2 and 661W cells to mimic the condition of RD in vitro, where A20 siRNA was adopted to knock down the A20 expression in BV-2 cells. Photoreceptor cells apoptosis, inflammatory response and microglia activity following RD with or without minocycline were evaluated. Photoreceptor cells apoptosis and inflammatory response were induced after RD, which could be largely counteracted by minocycline. Minocycline postponed the migration and proliferation of microglia and facilitated their transition to the M2 subtype following RD. Blocking A20 expression in BV-2 cells with siRNA crippled the effect of minocycline. Collectively, minocycline yields a promoting effect on photoreceptor cells survival post-RD by modulating the transformation of microglia phenotypes, in which process A20 may play a "bridge" role.

Keywords: A20; Inflammatory response; Microglia; Minocycline; Retinal detachment.