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Neuroprotection from optic nerve injury and modulation of oxidative metabolism by transplantation of active mitochondria to the retina.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 4.2 ) Pub Date : 2020-01-15 , DOI: 10.1016/j.bbadis.2020.165686
Gabriel Nascimento-Dos-Santos 1 , Eduardo de-Souza-Ferreira 2 , Rafael Lani 1 , Caroline Coelho Faria 1 , Victor Guedes Araújo 1 , Leandro Coelho Teixeira-Pinheiro 1 , Taliane Vasconcelos 2 , Thaís Gonçalo 1 , Marcelo Felippe Santiago 1 , Rafael Linden 1 , Antonio Galina 2 , Hilda Petrs-Silva 1
Affiliation  

Mitochondrial dysfunctions are linked to a series of neurodegenerative human conditions, including Parkinson's disease, schizophrenia, optic neuropathies, and glaucoma. Recently, a series of studies have pointed mitotherapy - exogenous mitochondria transplant - as a promising way to attenuate the progression of neurologic disorders; however, the neuroprotective and pro-regenerative potentials of isolated mitochondria in vivo have not yet been elucidated. In this present work, we tested the effects of transplants of active (as well-coupled organelles were named), liver-isolated mitochondria on the survival of retinal ganglion cells and axonal outgrowth after optic nerve crush. Our data show that intravitreally transplanted, full active mitochondria incorporate into the retina, improve its oxidative metabolism and electrophysiological activity at 1 day after transplantation. Moreover, mitotherapy increases cell survival in the ganglion cell layer at 14 days, and leads to a higher number of axons extending beyond the injury site at 28 days; effects that are dependent on the organelles' structural integrity. Together, our findings support mitotherapy as a promising approach for future therapeutic interventions upon central nervous system damage.

中文翻译:

通过将活性线粒体移植到视网膜上,对视神经损伤的神经保护和氧化代谢的调节。

线粒体功能障碍与一系列人类神经退行性疾病有关,包括帕金森氏病,精神分裂症,视神经病变和青光眼。最近,一系列研究表明线粒体疗法-外源性线粒体移植-是减轻神经系统疾病进展的一种有前途的方法。但是,尚未阐明体内分离的线粒体的神经保护和再生潜力。在这项目前的工作中,我们测试了活动性(耦合良好的细胞器)移植,肝隔离的线粒体移植对视神经挤压后视网膜神经节细胞存活和轴突生长的影响。我们的数据表明,玻璃体内移植的完整活动线粒体并入视网膜,移植后1天改善其氧化代谢和电生理活性。此外,线粒体疗法在14天时可增加神经节细胞层的细胞存活率,并在28天时导致更多的轴突延伸超出损伤部位。影响取决于细胞器的结构完整性。总之,我们的发现支持线粒体疗法作为中枢神经系统受损的未来治疗干预的一种有前途的方法。
更新日期:2020-01-15
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