MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells

Molecular Therapy: Nucleic Acids

Shuk Han Ng¹  Chi Chiu Wang²  Tin Lap Lee³  Christopher Kai-shun Leung³  Jasmine S.Y. Yung⁴  Xu Cao⁴  Tracy Y.C. Ho⁴  Heather K. Mak⁴  Tsz Kin Ng⁴  Wai Kit Chu⁴  Wing Ho Yung⁴  Robert N. Weinreb⁵  Kwong Wai Choy⁶ 

[1] Department of Ophthalmology, University of California, San Diego, La Jolla, CA, USA;Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Hong Kong, PRC;Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, PRC;Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, PRC;Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA;School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, PRC;

关键词: retinal ganglion cells;    microRNA-19;    phosphatase and tensin homolog;    PTEN;    axon regenerative capacity;    axon regeneration;   

DOI  :  

来源: DOAJ

【 摘 要 】

Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies.

【 授权许可】

Unknown