期刊
ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 36, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202104141
关键词
brain-derived neurotrophic factor; glaucoma; microRNA-22-3p; neuroprotection; tetrahedral frame nucleic acids
类别
资金
- National Key RAMP
- D Program of China [2019YFA0110600]
- National Natural Science Foundation of China [81970916, 81671031]
- National Major Scientific Equipment Program [2012YQ12008005]
The study demonstrated that tetrahedral frame nucleic acids (tFNAs) - modified miR-22 can effectively treat glaucoma by activating the TrkB-BDNF signaling pathway to restore damaged retinal neurons' protective function.
Glaucoma is the world's leading irreversible cause of blindness. It is characterized by progressive retinal ganglion cells (RGCs) loss and axon damage, and there is no effective prevention or treatment so far. In this study, tetrahedral frame nucleic acids (tFNAs) with various biological functions are selected as the carrier, and microRNA-22-3p (miR-22) are modified by attaching them onto tFNAs to synthesize a novel DNA nanocomplex (tFNAs-miR22). Relevant results show that tFNAs can efficiently transfer miR-22 into damaged retinal neurons to impose a neuroprotective effect on glaucoma. More interestingly, a certain synergism between tFNAs and miR-22 is shown. tFNAs-miR22 can selectively activate tyrosine kinase receptor B (TrkB) and regulate the TrkB-brain-derived growth factor (BDNF) signaling pathway to restore the expression of BDNF on the models of N-methyl-D-aspartate (NMDA)-induced glaucoma in vivo and in vitro, thus exerting the neuroprotective effect on retinal neurons. This study shows the successfully establishment of a simple but effective delivery system of microRNAs associated with glaucoma treatment, which may be a promising neuroprotective agent for future treatment of this optic neurodegenerative disease.
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