Role of interleukin-1[beta] in hypoxia-induced depression of glutamate uptake in retinal Müller cells

It is suggested that hypoxic-ischemic retinal diseases induce loss of retinal ganglion cells. Excess glutamate release is involved in these conditions. A predominant function of Müller cells is to regulate glutamate levels, but in these diseases the function is compromised. The present study was performed to investigate the role of interleukin-1[beta](IL-1[beta])on the glutamate uptake in retinal Müller cells under hypoxia and to study the possible mechanism. The levels of IL-1[beta],Kir4.1, and GLAST in retinal Müller cells under hypoxia were analyzed by Western blotting and realtime-RT-PCR, and glutamate uptake assay was undertaken to investigate the activity of GLAST. After being treated with IL-1[beta]under normoxia, these proteins (Kir4.1 and GLAST) and their mRNAs, and glutamate uptake activity in Müller cells were investigated. To confirm the effect of IL-1[beta]on glutamate uptake activity in Müller cells, addition of IL-1ra was used. Under hypoxia, Müller cells glutamate uptake, Kir4.1 and GLAST expressions were decreased significantly; however, IL-1[beta]expression was increased. IL-1[beta]treatment induced depression of glutamate uptake, decrease of Kir4.1 and GLAST expressions in retinal Müller cells under normoxia. Moreover, addition of IL-1ra significantly ameliorated decreases in Kir4.1 and GLAST expressions, and compromise of glutamate uptake activity in retinal Müller cells under hypoxia. These findings indicated that decreases in Kir4.1 and GLAST expressions and depression of glutamate uptake in retinal Müller cells under hypoxia may be induced by the inflammatory cytokine IL-1[beta].[PUBLICATION ABSTRACT]