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视网膜变性8突变不会在表型上改变小鼠自身免疫性视神经炎。

Murine Autoimmune Optic Neuritis Is Not Phenotypically Altered by the Retinal Degeneration 8 Mutation.

作者信息

Stojic Aleksandar, Fairless Richard, Beck Susanne C, Sothilingam Vithiyanjali, Weissgerber Petra, Wissenbach Ulrich, Gimmy Valerie, Seeliger Mathias W, Flockerzi Veit, Diem Ricarda, Williams Sarah K

机构信息

Department of Neurology, University Clinic Heidelberg, Heidelberg, Germany.

Division of Ocular Neurodegeneration, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.

出版信息

Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):318-328. doi: 10.1167/iovs.16-20419.

Abstract

PURPOSE

To investigate whether the presence of the retinal degeneration 8 (rd8) mutation in C57BL/6 mice alters the phenotype of autoimmune optic neuritis (AON).

METHODS

C57BL/6J and C57BL/6N mice were genotyped for the rd8 mutation and fundus analyses and examination of retinal layer morphology were performed in vivo by scanning laser ophthalmoscopy and optical coherence tomography. Visual function was assessed by recording electroretinographs, and visual evoked potentials and retinae and optic nerves were assessed histopathologically. Retinal ganglion cell numbers were determined by retrograde labeling with fluorogold. Mice were then immunized with myelin oligodendrocyte glycoprotein 35-55 to induce AON before assessment of retinal ganglion cell degeneration, inflammatory infiltration of retinae and optic nerves, and demyelination. Furthermore, visual function was assessed by visual evoked potentials.

RESULTS

All C57BL/6N mice were homozygous for the mutation (Crb1rd8/rd8) and had pathology typical of the rd8 mutation; however, this was not seen in the C57BL/6J (Crb1wt/wt) mice. Following induction of AON, no differences were seen between the Crb1rd8/rd8 and Crb1wt/wt mice regarding disease parameters nor regarding inner retinal degeneration either in the retina as a whole or in the inferior nasal quadrant.

CONCLUSIONS

The presence of the rd8 mutation in C57BL/6 mice does not affect the course of AON and should not provide a confounding factor in the interpretation of experimental results obtained in this model. However, it could be dangerous in other models of ocular pathology.

摘要

目的

研究C57BL/6小鼠中视网膜变性8(rd8)突变的存在是否会改变自身免疫性视神经炎(AON)的表型。

方法

对C57BL/6J和C57BL/6N小鼠进行rd8突变基因分型,并通过扫描激光检眼镜和光学相干断层扫描在体内进行眼底分析和视网膜层形态检查。通过记录视网膜电图评估视觉功能,通过组织病理学评估视觉诱发电位以及视网膜和视神经。通过用荧光金逆行标记确定视网膜神经节细胞数量。然后用髓鞘少突胶质细胞糖蛋白35 - 55免疫小鼠以诱导AON,之后评估视网膜神经节细胞变性、视网膜和视神经的炎性浸润以及脱髓鞘情况。此外,通过视觉诱发电位评估视觉功能。

结果

所有C57BL/6N小鼠均为该突变的纯合子(Crb1rd8/rd8),具有rd8突变的典型病理学特征;然而,在C57BL/6J(Crb1wt/wt)小鼠中未观察到这种情况。诱导AON后,Crb1rd8/rd8和Crb1wt/wt小鼠在疾病参数以及整个视网膜或鼻下象限的视网膜内层变性方面均未观察到差异。

结论

C57BL/6小鼠中rd8突变的存在不影响AON的病程,在解释该模型中获得的实验结果时不应构成混杂因素。然而,在其他眼部病理学模型中可能存在危险。

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