Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush

• Published in: Neuropharmacology 2018-07, Vol.137, p.33-49
• Main Authors: Li, Hong-Jiang, Pan, Yuan-Bo, Sun, Zhao-Liang, Sun, Yi-Yu, Yang, Xi-Tao, Feng, Dong-Fu
• Format: Article
• Language: English
• Subjects: Astrocyte activation; Axonal regeneration; EGFR pathway; Glial scar; microRNA-21; Optic nerve crush
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2018.04.028

Optic nerve injury is a leading cause of irreversible visual impairment worldwide and can even cause blindness. Excessive activation of astrocytes has negative effects on the repair and recovery of retinal ganglion cells following optic nerve injury. However, the molecular and cellular mechanisms underlying astrocyte activation after optic nerve injury remain largely unknown. In the present study, we explored the effects of microRNA-21 (miR-21) on axon regeneration and flash visual evoked potential (F-VEP) and the underlying mechanisms of these effects based on astrocyte activation in the rat model of optic nerve crush (ONC). To the best of our knowledge, this article is the first to report that inhibition of miR-21 enhances axonal regeneration and promotes functional recovery in F-VEP in the rat model of ONC. Furthermore, inhibition of miR-21 attenuates excessive astrocyte activation and glial scar formation, thereby promoting axonal regeneration by regulating the epidermal growth factor receptor (EGFR) pathway. In addition, we observed that the expression of tissue inhibitor of metalloproteinase-3, a target gene of miR-21, was inhibited during this process. Taken together, these findings demonstrate that inhibition of miR-21 regulates the EGFR pathway, ameliorating excessive astrocyte activation and glial scar progression and promoting axonal regeneration and alleviating impairment in F-VEP function in a model of ONC. This study's results suggest that miR-21 may represent a therapeutic target for optic nerve injury. [Display omitted] •Inhibition of miR-21 enhances axon regeneration and promotes functional recovery of F-VEP in a rat model of ONC.•Inhibition of miR-21 attenuates excessive astrocyte activation and glial scar formation, thus promoting axon regeneration.•miR-21-mediated activation of the EGFR/PI3K/AKT pathway is involved in astrocyte activation after ONC.•Tissue inhibitor of metalloproteinase-3, a target gene of miR-21, was inhibited during the procedure.