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.
Department of Ophthalmology, The Affiliated Cixi Hospital of Wenzhou Medical University, 315300, Cixi, Zhejiang, China.
Chongda
C
Chen
Hui
H
Chen
Chunliu
C
Xu
Yisheng
Y
Zhong
Xi
X
Shen
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D063928:Ependymoglial Cells / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D053583:Interleukin-1beta / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000098854:Kcnj10 Channel
D027341:Excitatory Amino Acid Transporter 1; D053583:Interleukin-1beta; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid