Inhibiting autophagy by miR-19a-3p/PTEN regulation protected retinal pigment epithelial cells from hyperglycemic damage.

Jul 03, 2023

Experts: Qiaoyun Gong,Dawei Luo,Haiyan Wang,Xun Xu,Ying Fan,Zhi Zheng,Tianwei Qian

The catabolic process of autophagy is arousing the attention of researchers studying diabetic retinopathy (DR), but the role and molecular mechanism of autophagy in DR are still unclear.
An in vivo diabetic rat model and in vitro hyperglycemic-exposed retinal pigment epithelium (RPE) cell cultures were established to mimic early DR. Transmission electron microscopy and mRFP-GFP-LC3 adenovirus transfection were applied for autophagic flux analysis. MicroRNA (miR)-19a-3p, members of the phosphate and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR) pathway, and the autophagy-related proteins light chain (LC)3II/I and p62 were detected. Annexin V, transwell, Cell Counting Kit-8, fluorescein isothiocyanate-dextran monolayer permeability assay, and transepithelial electrical resistance were performed to evaluate the effects of regulating autophagy on RPE cells under the DR condition.
Autophagy was aberrantly activated in DR as evidenced by autophagosome accumulation. Further mechanistic experiments revealed that DR induced PTEN expression, thus inhibiting Akt/mTOR phosphorylation and stimulating aberrant autophagy and apoptosis. Notably, these events could be reversed by miR-19a-3p directly targeting PTEN. Downregulation of autophagy by miR-19a-3p overexpression, PTEN knockdown, or 3-methyladenine (3-MA) treatment inhibited autophagosome formation and thus effectively ameliorated hyperglycemia-induced RPE cell apoptosis, increased migration, inhibited viability, and enhanced monolayer permeability under the DR condition.
Our findings suggest that upregulation of miR-19a-3p inhibits aberrant autophagy by directly targeting PTEN, thus protecting RPE cells against DR damage. miR-19a-3p may represent a novel therapeutic target for inducing protective autophagy in early DR.

Copyright © 2023. Published by Elsevier B.V.

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ABOUT THE EXPERTS

Qiaoyun Gong,Dawei Luo,Haiyan Wang,Xun Xu,Ying Fan,Zhi Zheng,Tianwei Qian

Qiaoyun Gong

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.

Dawei Luo

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.

Haiyan Wang

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.

Xun Xu

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China.

Ying Fan

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China. Electronic address: fanying0129@163.com.

Zhi Zheng

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China. Electronic address: zzheng88@sjtu.edu.cn.

Tianwei Qian

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, China. Electronic address: qtw6180@126.com.