中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (3): 690-696.doi: 10.4103/1673-5374.320989

• 原著:视神经损伤修复保护与再生 • 上一篇    

OTX2刺激成体视网膜神经节细胞再生

  

  • 出版日期:2022-03-15 发布日期:2021-10-15

OTX2 stimulates adult retinal ganglion cell regeneration

Raoul Torero Ibad*, †, Nicole Quenech’du, Alain Prochiantz‡, Kenneth L. Moya*   

  1. Centre for Interdisciplinary Research in Biology (CIRB), Collége de France, CNRS UMR 7241, INSERM U1050, Labex MemoLife, Paris Sciences et Lettres Research University, Paris, France
    †Current address: Univ. Lille, CNRS, UMR 8523 - PhLAM - Physique des Lasers Atomes et Molécules, F-59000 Lille, France
    ‡Current address: BrainEver, 74 rue du Faubourg Saint Antoine, 75012 Paris and Institute of Neurosciences, 320 Yeu Yang Rd, Shanghai 200031, China
  • Online:2022-03-15 Published:2021-10-15
  • Contact: Raoul Torero Ibad, PhD, raoul.torero@univ-lille.fr; Kenneth L. Moya, PhD, ken.moya@college-de-france.fr.
  • Supported by:
     This work was supported by Fovea-Pharmaceuticals, and Global Research Laboratory Program Grant 2009-00424 from the Korean Ministry of Education, Science, and Technology, HOMEOSIGN: ERC-2013-AdG n°339379 and NeuroprOtx: ANR-16-CE16-0003-02.

摘要:

OTX2是视网膜中表达的一种同源蛋白转录因子,以前的研究表明,外源OTX2可促进视网膜损伤后神经节细胞的体外和体内存活率。实验量化了OTX2体外和体内对成体视网膜神经节细胞轴突再生的影响。结果表明,外源性OTX2刺激离体成体视网膜细胞培养物和成体视网膜组织外植体中视网膜神经节细胞的轴突再生,并且在成年大鼠视网膜神经节细胞的培养物中观察到视网膜神经节细胞对OTX2产生直接反应,OTX2对视神经压迫后14天内直至视交叉的再生轴突数量具有积极作用,OTX2对视网膜神经节细胞存活和再生的作用对于影响这种细胞类型的退行性疾病具有潜在的意义。

https://orcid.org/0000-0002-7598-6180 (Raoul Torero Ibad)

Abstract: Retinal ganglion cell (RGC) axons provide the only link between the light sensitive and photon transducing neural retina and visual centers of the brain. RGC axon degeneration occurs in a number of blinding diseases and the ability to stimulate axon regeneration from surviving ganglion cells could provide the anatomic substrate for restoration of vision. OTX2 is a homeoprotein transcription factor expressed in the retina and previous studies showed that, in response to stress, exogenous OTX2 increases the in vitro and in vivo survival of RGCs. Here we examined and quantified the effects of OTX2 on adult RGC axon regeneration in vitro and in vivo. The results show that exogenous OTX2 stimulates the regrowth of axons from RGCs in cultures of dissociated adult retinal cells and from explants of adult retinal tissue and that RGCs respond directly to OTX2 as regrowth is observed in cultures of purified adult rat RGCs. Importantly, after nerve crush in vivo, we observed a positive effect of OTX2 on the number of regenerating axons up to the optic chiasm within 14 days post crush and a very modest level of acuity absent in control mice. The effect of OTX2 on RGC survival and regeneration is of potential interest for degenerative diseases affecting this cell type. All animal procedures were approved by the local “Comié d’éιthique en expérimentation animale n°59” and authorization n° 00702.01 delivered March 28, 2014 by the French “Ministére de l’enseignement supérieur et de la recherche”.

Key words: axon regeneration, dissociated retinal culture, GAP-43, homeoprotein, optic nerve crush, OTX2, retinal explants, retinal ganglion cell

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