MicroRNA‐145‐5p targeting of TRIM2 mediates the apoptosis of retinal ganglion cells via the PI3K/AKT signaling pathway in glaucoma. (10th August 2021)

• Record Type: Journal Article
• Authors: Xu, Kai; Li, Sizhen; Yang, Qingsong; Zhou, Zixiu; Fu, Min; Yang, Xiaodong; Hao, Kuanxiao; Liu, Yating; Ji, Heqing
• Is Part Of: Journal of gene medicine. Volume 23:Number 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-10
• Subjects: apoptosis -- glaucoma -- miR‐145‐5p -- PI3K/AKT pathway -- RGCs -- TRIM2; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.3378
• Languages: English
• ISSNs: 1099-498X

Abstract

Abstract: Background: There is accumulating evidence to suggest that microRNAs (miRNAs) are associated with the progressive optic neuropathy including glaucoma. Apoptosis of retinal ganglion cells (RGCs) is a hallmark of glaucoma. The present study focused on the effects of miR‐145‐5p on RGC apoptosis in glaucoma. Methods: We established a glaucoma rat model by intraocular injection of N ‐methyl‐d ‐aspartic acid (NMDA). RGCs were isolated from newborn rats and treated with NMDA. Hematoxylin and eosin staining was performed to detect morphological changes in the retinas of rats. The expression of miR‐145‐5p and tripartite motif‐containing 2 (TRIM2) in RGCs was measured by RT‐qPCR. The viability of RGCs was measured by MTT assay. Flow cytometry analysis and TUNEL assays were conducted to assess the apoptosis of RGCs. The interaction between miR‐145‐5p and TRIM2 was investigated using a luciferase reporter assay. Results: Rats injected with NMDA showed a thinner ganglion cell layer (GCL) and inner plexiform layer (IPL) as well as increased expression of miR‐145‐5p. Silencing of miR‐145‐5p significantly increased the GCL and IPL in the glaucoma rat model. Moreover, miR‐145‐5p expression was upregulated in RGCs ex vivo in response to NMDA. Silencing of miR‐145‐5p promoted cell viability and suppressed apoptosis in NMDA‐treated RGCs. Mechanistically, miR‐145‐5p targeted the TRIM2 3′ untranslated region to suppress its expression. TRIM2 was upregulated in NMDA‐treated RGCs and protected RGCs against NMDA‐induced apoptosis. Furthermore, miR‐145‐5p suppressed the PI3K/AKT pathway by downregulating TRIM2 in NMDA‐treated RGCs. Conclusions: Suppression of miR‐145‐5p inhibited the apoptosis of RGCs via TRIM2‐mediated activation of the PI3K/AKT signaling pathway in NMDA‐induced glaucoma. Abstract : NMDA‐induced miR‐145‐5p targets the TRIM2 3′ untranslated region to suppress its expression and further inactivate the PI3K/AKT pathway, inhibiting the viability and promoting the apoptosis of retinal ganglion cells.