Suppression of astrocyte elevated gene-1 protects against light-induced photoreceptor apoptosis and inflammation in retina

Abstract

Purpose

To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.

Methods

The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.

Results

AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.

Conclusions

AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.