title: Alterations in neurofilament light in optic nerve in rat kainate and monkey ocular hypertension models.
abstract: The purpose of this study is to evaluate the changes in neurofilament light (NF-L) protein in the optic nerve in rat kainate and monkey ocular hypertension models. In the rat model, optic nerve damage was induced by kainate injection into the vitreous body. In the monkey model, photocoagulation of the trabecular meshwork led to laser-induced ocular hypertension. NF-L in optic nerve extract was quantified by quantitative immunoblot using an imaging analyzer. The amount of NF-L in optic nerve was compared between normal and kainate-treated groups at 7 days after kainate injection. Specimens from rat optic nerves and retinas were evaluated histologically to examine the correlations between damage and amount of NF-L in the optic nerve. In monkeys, the amount of NF-L in the optic nerve was compared between control fellow and ocular hypertensive eyes. Injection of kainate induced morphological optic nerve and retinal damage in rats. The amount of NF-L in the optic nerve was significantly reduced in kainate-treated eyes (vs. normal eyes). The amount of NF-L correlated with the cell count in the ganglion cell layer and the axon number in the optic nerve at 7 days after kainate injection. Further, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non N-methyl-D-aspartate receptor antagonist, suppressed the kainate-induced reduction in NF-L and retinal damage. In the monkey model, ocular hypertension and morphological optic nerve damage were shown by laser-treated eyes. The amount of NF-L in the optic nerve was reduced in laser-treated eyes. In conclusion, in rat kainate and monkey ocular hypertension models, immunoblot evaluation of NF-L shows the reduction of the amount of NF-L in the optic nerves of treated-eyes. The amount of NF-L correlated with the morphological retinal and optic nerve damage in rats. These findings indicate that immunoblot evaluation of NF-L in the optic nerve may provide a quantitative index of optic nerve damage.
authors.affiliation: Glaucoma Group, Research and Development Center, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma, Nara 630-0101, Japan.
authors.forename: Takazumi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000918:Antibody Specificity; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid; D008252:Macaca fascicularis; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D016900:Neurofilament Proteins / Q000276:immunology / Q000378:metabolism*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016900:Neurofilament Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H; C061195:neurofilament protein M; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007608:Kainic Acid