Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush
| Autor: | Zhao-Liang Sun, Yi-Yu Sun, Hong-Jiang Li, Xi-Tao Yang, Yuan-Bo Pan, Dong-Fu Feng |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male genetic structures Retinal ganglion Glial scar Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience Cicatrix Random Allocation 0302 clinical medicine medicine Animals Epidermal growth factor receptor Axon Evoked potential Cells Cultured Pharmacology biology Chemistry Regeneration (biology) Optic Nerve Axons Cell biology Nerve Regeneration ErbB Receptors Disease Models Animal MicroRNAs 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents Astrocytes Optic Nerve Injuries biology.protein Optic nerve Evoked Potentials Visual 030217 neurology & neurosurgery Astrocyte |
| Zdroj: | Neuropharmacology. 137 |
| ISSN: | 1873-7064 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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