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Miscellaneous (34)

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Abstract #78960 Published in IGR 20-1

Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma

Nie XG; Fan DS; Huang YX; He YY; Dong BL; Gao F
American Journal of Physiology and Cell Physiology 2018; 315: C839-C849

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Glaucoma represents a major cause of blindness, generally associated with elevated intraocular pressure (EIOP). The aim of the present study was to investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs) and the underlying mechanism based on a mouse model of chronic glaucoma with EIOP. The successfully modeled mice were administered with mimics or inhibitors of miR-149. Next, the number of RGCs, ultrastructural changes of RGCs, and purity of RGCs in the retinal tissues were detected. Moreover, the RGCs were collected and subsequently treated with 60 mmHg pressure and transfected with a series of plasmids aiding in the regulation of the expression of miR-149 and betacellulin (BTC). The levels of miR-149, BTC, phosphatidylinositol 3-kinase (PI3K), and Akt were subsequently determined. Finally, RGC viability and apoptosis were detected accordingly. Dual luciferase reporter gene assay provided validation, highlighting BTC was indeed a target gene of miR-149. The downregulation of miR-149 is accompanied by an increased number of RGCs and decreased ultrastructural RGC alterations. Additionally, downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in both the retinal tissues and RGCs, whereas the silencing of miR-149 was observed to promote the viability of RGC and inhibit RGC apoptosis. Taken together, the results of the current study provided validation suggesting that the downregulation of miR-149 confers protection to RGCs by means of activating the PI3K/Akt signaling pathway via upregulation of BTC in mice with glaucoma. Evidence presented indicated the promise of miR-149 inhibition as a potential therapeutic strategy for glaucoma treatment.

Department of Ophthalmology, Luoyang Central Hospital , Luoyang , People's Republic of China.

Full article

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Classification:

3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)

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