Inhibition of LOX-1 prevents inflammation and photoreceptor cell death in retinal degeneration

Abstract Purpose To explore the expression and role of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in retinal degeneration. Methods The retinal degeneration of BALB/c mice was induced by light exposure. BV2 cells were activated by LPS stimulation. Retinas or BV2 cells were pretreated with LOX-1 neutralizing antibody or Polyinosinic acid (PolyI) (the inhibitor of LOX-1) before light damage (LD) or LPS stimulation. LOX-1, TNF-α, IL-1β, CCL2 and NF-κB expression were detected in retinas or BV2 cells by real-time RT-PCR, western blot or ELISA. Histological analyses of retinas were performed. Photoreceptor cell death was assessed by TUNEL assay in retinas or by flow cytometry in 661W cells cultured in microglia-conditioned medium. Results Photoreceptor cell death and elevated expression of LOX-1 were induced by LD in retinas of BALB/c mice. LOX-1 neutralizing antibody or PolyI pretreatment significantly reduced the elevated expression of LOX-1, TNF-α, IL-1β, CCL2 and p-NF-κB caused by LD in retinas. Inhibition of LOX-1 by LOX-1 neutralizing antibody or PolyI significantly reduced photoreceptor cell death induced by LD in retinas. Elevated levels of TNF-α, IL-1β and CCL2 caused by LPS were down-regulated by inhibition of LOX-1 in BV2 cells. Inhibition of LOX-1 reduces microglial neurotoxicity on photoreceptors. Conclusions LOX-1 expression is increased in light induced retinal degeneration, what’s more, inhibition of LOX-1 prevents inflammation and photoreceptor cell death in retinal degeneration and reduces microglial neurotoxicity on photoreceptors. Therefore, LOX-1 can be used as a potential therapeutic target for such retinal degeneration diseases.