Interleukin-1beta mediates ischemic injury in the rat retina.
Two types of experiment were performed to examine the role of interleukin-1beta in ischemia-induced damage in the rat retina. In the in vivo study, enzyme-linked immunosorbent assay was used to investigate the expression of immunoreactive interleukin-1beta in the rat retina following a hypertension-induced ischemia/reperfusion, while the effect of a recombinant human interleukin-1 receptor antagonist or an anti-interleukin-1beta neutralizing antibody on the ischemia-induced damage was examined histologically. A transient increase in the expression of immunoreactive interleukin-1beta was observed in the retina 3-12 hr after reperfusion, and morphometric evaluation at 7 days after the ischemia showed a decrease in cell numbers in the ganglion cell layer and a decreased thickness of the inner plexiform layer with no change in the other retinal layers. Intravitreal injection of interleukin-1 receptor antagonist (1 or 10 ng per eye) or anti-interleukin-1beta antibody (50 or 500 ng per eye) 5 min before the onset of the ischemia reduced the damage. In the in vitro study, interleukin-1 receptor antagonist (500 ng ml(-1)) significantly reduced glutamate-induced neurotoxicity in rat cultured retinal neurons. These results suggest that interleukin-1 plays an important role in mediating ischemic and excitotoxic damage in the retina, and that interleukin-1 inhibitors may be therapeutically useful against neuronal injury caused by optic nerve or retinal diseases such as glaucoma and central retinal artery or vein occlusion.
Yoneda
S
S
Ophthalmic Research Division, Santen Pharmaceuticals Co. Ltd, 8916-16, Takayama, Ikoma 630-0101, Japan.
Tanihara
H
H
Kido
N
N
Honda
Y
Y
Goto
W
W
Hara
H
H
Miyawaki
N
N
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002831:Choroid Plexus / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D017950:Ganglia, Sensory / Q000473:pathology; D018698:Glutamic Acid / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology
D007375:Interleukin-1; D018698:Glutamic Acid; D016291:Dizocilpine Maleate