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Yoshiko Matsumoto, Akiyasu Kanamori, Makoto Nakamura, Ichiro Nakashima, Akira Negi; Impact of plasma from patients with neuromyelitis optica spectrum disorders on the optic degeneration in rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1416.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the impact of an anti-aquaporin 4 (AQP4) antibody obtained from plasma of patients with neuromyelitis optica spectrum disorders (NMOSDs) on the rodent optic nerve.
We collected plasma from patients with idiopathic or NMO-optic neuritis or from normal subjects. An anti-aquaporin 4 (AQP4) antibody in blood was measured by a cell-based assay. After the rat optic nerve was exposed, the sheath was cut about 1mm. The collected plasma was injected underneath the optic sheath, and then Medical Quick Absorber® soaked with plasma was left beside the optic nerve. The treated rats were divided into three groups based on the plasma samples: AQP4 -seropositive (AQP4+), AQP4 seronegative (AQP4-) and normal subjects (control). Seven days (7D) and 14 days (14D) after the treatment, rats were sacrificed and the optic nerves and retinas were excised. Cryosections were subjected to immunhistochemistry against neurofilament (NF), glial fibrillary acidic protein (GFAP), CD 11, and AQP4. Real-time polymerase chain reaction alayses was also conducted to evaluate their gene expressions. In some groups of rats, retinal ganglion cells (RGCs) labeled from the superior colliculus with fluoro-gold were quantified on whole-mounted retinas at 14D.
The RGC density (938/mm2) in the AQP4+ group was significantly decreased compared with AQP4- (1804/mm2) and control group (2086/mm2) (n=4, p<0.001). The number of microglia, defined as the CD11 positive cells, was increased in AQP4+ group (n=4, p<0.001). Evaluated by the intensity of fluorescein in the optic nerve, NF at 14D (p=0.005), AQP4 at 7D (p=0.016) and GFAP (p=0.026) at 7D were decreased in AQP4+ group. The gene expression of NF in both optic nerve and retina were decreased in AQP4+ group at 14D (p=0.027).
In the present study, the AQP4 antibody-positive plasma decreased expression of GFAP and AQP4 in astrocytes, which coincided with reduction of the RGC density and the nerve fibers in the optic nerve. These findings further implicated in the direct pathological role of the AQP4 antibody in the optic nerve degeneration associated with NMOSDs.
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