Citation:Shao WY,Liu X,Gu XL,Ying X,Wu N,Xu HW,Wang Y.Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve.Int J Ophthalmol 2016;9(7):955-966,doi:10.18240/ijo.2016.07.04
Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve
Received:March 12, 2016  Revised:May 25, 2016
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DOI:10.18240/ijo.2016.07.04
Key Words:αA-crystallin  axonal regeneration  astrocyte  glial scar  chondroitin sulfate proteoglycans  optic nerve crush
Fund Project:Supported by the National Nature Science Foundation of China (No.81270996).
                    
AuthorInstitution
Wei-Yang Shao Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
Xiao Liu Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
Xian-Liang Gu Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
Xi Ying Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
Nan Wu Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
Hai-Wei Xu Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
Yi Wang Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing , China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing , China
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Abstract:
      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 Sprague-Dawley 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 14d after ONC, and the glial fibrillary acidic protein (GFAP) levels in the retina and crush site were analyzed 1, 3, 5, 7 and 14d 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 14d 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 αA-crystallin markedly promoted axon regeneration in ONC rats and enhanced the regenerated axons penetrated into the glial scar. CSPGs and neurocan expression also decreased 14d 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.

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