1. Amino-Nogo Inhibits Optic Nerve Regeneration and Functional Recovery via the Integrin αv Signaling Pathway in Rats
- Author
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Xiao-Lei Yin, Shu-Xing Ji, Chun-lin Chen, Yuan-Guo Zhou, Xiao-Feng Cai, Jian Ye, Rong-Di Yuan, Min Lang, Wei Liu, Huan Zou, Zheng Zheng, and Yan Huo
- Subjects
Retinal Ganglion Cells ,medicine.medical_specialty ,Nogo Proteins ,Physiology ,Optic nerve ,Integrin ,lcsh:Physiology ,Rats, Sprague-Dawley ,Focal adhesion ,lcsh:Biochemistry ,Internal medicine ,mental disorders ,medicine ,Animals ,lcsh:QD415-436 ,RNA, Small Interfering ,Axon ,Integrin Signaling Pathway ,biology ,lcsh:QP1-981 ,Chemistry ,Signaling pathway ,Integrin alphaV ,Peptide Fragments ,Nerve Regeneration ,Rats ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,Retinal ganglion cell ,Gene Knockdown Techniques ,Optic Nerve Injuries ,biology.protein ,Amino-Nogo ,Evoked Potentials, Visual ,Signal transduction ,Axonal regeneration ,Myelin Proteins ,psychological phenomena and processes ,Signal Transduction - Abstract
Background: Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo. Methods: Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated. Results: Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group. Conclusion: These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.
- Published
- 2015