MicroRNA-19a-PTEN axis is involved in the developmental decline of axon regenerative capacity in retinal ganglion cells
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AbstractIrreversible 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. Here, 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 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 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 demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity via intravitreal injection in patients with optic neuropathies.
Acceptance Date28/05/2020
All Author(s) ListMak Heather K, Yung Jasmine S Y, Weinreb Robert N, Ng Shuk Han, Cao Xu, Ho Tracy Y C, Ng Tsz Kin, Chu Wai Kit, Yung Wing Ho, Choy Kwong Wai, Wang Chi Chiu, Lee Tin Lap, Leung Christopher Kai Shun
Journal nameMolecular Therapy - Nucleic Acids
Volume Number21
Pages251 - 263
LanguagesEnglish-United Kingdom
KeywordsRetinal ganglion cells, microRNA-19, Phosphatase and tensin homolog, axon regenerative capacity, adeno-associated virus, optic nerve crush

Last updated on 2021-15-09 at 00:00