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Yoshiko Matsumoto, Akiyasu Kanamori, Sho Nobuyoshi, Ichiro Nakashima, Makoto Nakamura; Impaired axonal transport in a rodent model of optic neuritis due to NMO spectrum disorder. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5530.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported that exposure of serum from patients with seropositive neuromyelitis optica spectrum disorders (NMOSDs) led to astrocytic damage at 7 days. However, axonal loss was not detected at that time (Matsumoto Y, et al. Exp. Eye Res. 2014). The purpose of this study was to evaluate whether axonal transport is impaired in a rodent model of optic neuritis in NMOSDs.
We collected serum from patients with idiopathic or NMO-optic neuritis or from normal subjects. Using male Sprague-Dawley rats (200-300g), we exposed the rat optic nerve to the collected serum as previously reported. The treated rats were divided into those exposed to aquaporin 4 (AQP4) autoantibody-positive serum (AQP4+) or those exposed to AQP4 antibody-negative serum (AQP4-). Seven days (7D) and 14 days (14D) after treatment, rats were sacrificed and the optic nerves were excised. Cryosections of the optic nerves were subjected to immunohistochemistry against neurofilament (NF) and kinesin1-kif5b (Kif5b). Real-time polymerase chain reaction (RT-PCR) analyses were also conducted to evaluate Kif5b gene expressions.
Linear Ki5b immunoreactivity (IR) was co-localized with NF expression in the optic nerves. Aggregated IR of Kif5b was scattered in the optic nerves of the AQP4+ group at 7D. The number of the aggregated Kif5b IR in the AQP4+ group was statistically increased than that in the AQP4- group (n=8 each, unpaired t-test; p=0.02). The gene expression of Kif5b was significantly decreased in the AQP4+ group at 14D compared with controls (n=6 each, unpaired t-test; p=0.02), but not in the AQP4- group.
Given that kinesin1-Ki5b plays a critical role in the anterograde axonal transport, the present study suggested that axonal transport is impaired in the optic nerves of rodent models of NMOSDs before detectable axonal loss.
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