中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 1009-1016.doi: 10.4103/1673-5374.355753

• 综述:视神经损伤修复保护与再生 • 上一篇    下一篇

病理视网膜中的髓鞘细胞器:普遍存在和在眼部蛋白质稳态维持中的双重作用

  

  • 出版日期:2023-05-15 发布日期:2022-11-01

Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

Marina G. Yefimova1, 2, *    

  1. 1Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St-Petersburg, Russia;  2Laboratoire STIM CNRS ERL 7003, Université de Poitiers, Poitiers, France
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Marina G. Yefimova, PhD, DSci, HDR, yefimova3@gmail.com.

摘要: https://orcid.org/0000-0001-9036-4489 (Marina G. Yefimova)

Abstract: The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

Key words: autophagy, Huntington’s disease, Müller cells, myelinosome-driven secretion, myelinosomes, ocular pathophysiology, proteostasis, retina, retinal pigmented epithelium, ubiquitin-proteasome system