title: Dual effects of interleukin-1beta on N-methyl-D-aspartate-induced retinal neuronal death in rat eyes.
abstract: In this study we determine if interleukin-1beta (IL-1beta) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Sprague-Dawley rats were anesthetized with inhalation of halothane, after which a single injection of 5 microl of IL-1beta (0.1 to 10 ng/eye) (and/or IL-1 receptor antagonist (IL-1ra)) for experimental eyes was administered. Two days later (or simultaneously), NMDA (20 nmol) was injected into the vitreous space. One week later, each eye was enucleated and transverse sections were subjected to morphometric analysis. Enzyme-linked immunosorbent assay (ELISA) was conducted for the determination of IL-1beta levels in retina. Immunohistochemical and immunoblot studies were also performed. In eyes that received an intravitreal injection of IL-1beta (0.1 to 10 ng/eye), significant thinning of the inner plexiform layer (IPL) was observed (P<0.05). Immunohistochemical and ELISA studies demonstrated upregulated expression of IL-1beta in retinas that had undergone NMDA injection. Treatment with 10 ng of IL-1ra induced a protective effect against NMDA-induced retinal damage. Pretreatment with IL-1beta induced a significant protective effect on NMDA-induced retinal damage. Our studies suggest that IL-1beta induces neuronal cell death directly, as shown by the protective effects of IL-1ra, but has a protective effect on NMDA-induced retinal damage indirectly after an incubation time of at least 2 days.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kido
authors.forename: M
authors.initials: M
authors.lastname: Inatani
authors.forename: M
authors.initials: M
authors.lastname: Honjo
authors.forename: S
authors.initials: S
authors.lastname: Yoneda
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Miyawaki
authors.forename: Y
authors.initials: Y
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Tanihara
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005128:Eye Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012795:Sialoglycoproteins / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D004338:Drug Combinations; D018690:Excitatory Amino Acid Agonists; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D012795:Sialoglycoproteins; D018698:Glutamic Acid; D016202:N-Methylaspartate