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.