High-glucose（HG）triggers of Autophagy Affects the Expression of NF-KB and Apoptosis in Müller Cells

Xun Xu, Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, 100 Haining Road, Shanghai, 200080, China

Xiaofeng Zhang, Department of Ophthalmology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou,China

E. Song, Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, 215021, China

Abstract
Purpose: Autophagy pathway might be involved in the production of pro-inﬂammatory cytokines and apoptosis in HG-stimulated Müller cells, though details of the mechanism remain largely not currently known.
Methods: In this experimental research, primary SD rat retinal Miller cells were exposed to normal glucose (NG) or 3 h, 6 h, 12 h, 24 h, 36 h of high glucose. LC3I/LC31I, P62, and Beclin-1 protein expression was examined by Western blot analysis in the various experimental groups. And in fluorescence microscopy experiments, autophagy was evaluated by the autophagy markers LC3I/LC3ll and P62. The formation of autophagosomes and autolysosomes were examined by electron microscopy. TUNEL assay was used to detect apoptosis in high glucose Müller cells. One-way analysis of variance was used to compare data between different groups.
Results: In the present study, the retinas Müller cell expose to HG for early stage (6h), HG increased autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, stimulating autophagic flux, meanwhile, protecting the cells from apoptosis and inflammation. However, decreased autophagy-related maker protein (Beclin-1 and LC3Ⅱ/LC3Ⅰ) and autophagic flux were detected in the HG-stimulated Müller cells at later time points (24 h) and 3MA, restrain autophagic can increase both apoptosis and NF-κB phosphorylation in the Müller cell.
Conclusions: These results highlight that HG regulates autophagy in different periods, and autophagy is a protective effect may account for the defense against Müller cell inflammation. This finding might be valuable for the study of DR pathogenesis.

Keywords
Müller cells; Autophagy; Diabetes retinopathy; Apoptosis; NF-KB

Cite this paper
Li Wang, Laiqing Xie, Xun Xu, Xiaofeng Zhang, E. Song, High-glucose（HG）triggers of Autophagy Affects the Expression of NF-KB and Apoptosis in Müller Cells , SCIREA Journal of Clinical Medicine. Volume 8, Issue 2, April 2023 | PP. 101-123. 10.54647/cm321032

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