Role of interleukin-1β in hypoxia-induced depression of glutamate uptake in retinal Müller cells.

Background: 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-1β(IL-1β)on the glutamate uptake in retinal Müller cells under hypoxia and to study the possible mechanism.

Methods: The levels of IL-1β,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-1βunder 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-1βon glutamate uptake activity in Müller cells, addition of IL-1ra was used.

Results: Under hypoxia, Müller cells glutamate uptake, Kir4.1 and GLAST expressions were decreased significantly; however, IL-1βexpression was increased. IL-1βtreatment 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.

Conclusions: 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-1β.