Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

AIM：To explore the effects of αA-crystallin in astrocyte gliosis after optic nerve crush（ONC） and the mechanism of α-crystallin in neuroprotection and axon regeneration.METHODS：ONC was established on the SpragueDawley rat model and αA-crystallin（10 -4 g/L,4 μL） was intravitreously injected into the rat model.Flash-visual evoked potential（F-VEP） was examined 14 d after ONC,and the glial fibrillary acidic protein（GFAP） levels in the retina and crush site were analyzed 1,3,5,7 and 14 d after ONC by immunohistochemistry（IHC） and Western blot respectively.The levels of beta Tubulin（TUJ1）,growth-associated membrane phosphoprotein-43（GAP-43）,chondroitin sulfate proteoglycans（CSPGs） and neurocan were also determined by IHC 14 d after ONC.RESULTS：GFAP level in the retina and the optic nerve significantly increased 1d after ONC,and reached the peak level 7d post-ONC.Injection of αA-crystallin significantly decreased GFAP level in both the retina and the crush site 3d after ONC,and induced astrocytes architecture remodeling at the crush site.Quantification of retinal ganglion cell（RGC） axons indicated αAcrystallin markedly promoted axon regeneration in ONC rats and enhanced the regenerated axons penetrated into the glial scar.CSPGs and neurocan expression also decreased 14 d after αA-crystallin injection.The amplitude（N1-P1） and latency（P1） of F-VEP were also restored.CONCLUSION：Our results suggest α-crystallin promotes the axon regeneration of RGCs and suppresses the activation of astrocytes.