Research progress on the mechanism and treatment of endoplasmic reticulum stress in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Hu Weiwen ,  Zhou Qiong

Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China;

Corresponding author：

Zhou Qiong, Email: zqndyfy@163.com

Keywords：

Diabetic retinopathy; Endoplasmic reticulum stress; Unfolded protein response; Inositol-requiring protein-1; Protein kinase RNA-like endoplasmic reticulum kinase; Activating transcription factor-6; Review

DOI：

10.3760/cma.j.cn511434-20240723-00279

Video：

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Abstract Full text Figures/Tables Video References Cited by

Diabetic retinopathy (DR), a neurovascular complication of diabetes, presents a multifaceted pathogenesis that encompasses numerous biological processes and molecular mechanisms. Endoplasmic reticulum stress (ERS) plays a critical role in the maintenance of cellular homeostasis, and diabetic neuro-microangiopathy is driven by high glucose, which activated ERS through the promotion of protein misfolding, oxidative stress, and disturbances in calcium homeostasis. ERS activates the unfolded protein response, thereby influencing the onset and progression of DR through modulating mitochondria-associated endoplasmic reticulum membranes, autophagy, apoptosis, microvascular function, oxidative stress, and inflammation pathways. Currently, the principal interventions against ERS comprise the modulation of the ERS signalling axis and its interactions with associated pathological processes such as autophagy, oxidative stress, and inflammation, through pharmacological and molecular mechanisms. These interventions are directly or indirectly shown to inhibit persistent ERS and are demonstrated to ameliorate DR. With the in-depth study of ERS and the research and development of various drugs for ERS, it is expected to bring novel insights and strategies for DR management in the future.

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6. Ming SL, Zhang S, Wang Q, et al. Inhibition of USP14 influences alphaherpesvirus proliferation by degrading viral VP16 protein via ER stress-triggered selective autophagy[J]. Autophagy, 2022, 18(8): 1801-1821. DOI: 10.1080/15548627.2021.2002101.
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8. Yang S, Jiang H, Bian W, et al. Bip-Yorkie interaction determines oncogenic and tumor-suppressive roles of Ire1/Xbp1s activation[J/OL]. Proc Natl Acad Sci USA, 2022, 119(42): e2202133119 [2022-10-10]. https://pubmed.ncbi.nlm.nih.gov/36215479/. DOI: 10.1073/pnas.2202133119.
9. Bahamondes Lorca VA, Bastidas Mayorga BD, Tong L, et al. UVB-induced eIF2α phosphorylation in keratinocytes depends on decreased ATF4, GADD34 and CREP expression levels[J/OL]. Life Sci, 2021, 286: 120044[2021-10-09]. https://pubmed.ncbi.nlm.nih.gov/34637792/. DOI: 10.1016/j.lfs.2021.120044.
10. Ren JL, Chen Y, Zhang LS, et al. Intermedin_1-53 attenuates atherosclerotic plaque vulnerability by inhibiting CHOP-mediated apoptosis and inflammasome in macrophages[J]. Cell Death Dis, 2021, 12(5): 436. DOI: 10.1038/s41419-021-03712-w.
11. Hayakawa-Ogura M, Tana, Nakagawa T, et al. GADD34 suppresses eIF2α phosphorylation and improves cognitive function in Alzheimer's disease-model mice[J]. Biochem Biophys Res Commun, 2023, 654: 112-119. DOI: 10.1016/j.bbrc.2023.02.077.
12. Chiang WC, Chan P, Wissinger B, et al. Achromatopsia mutations target sequential steps of ATF6 activation[J]. Proc Natl Acad Sci USA, 2017, 114(2): 400-405. DOI: 10.1073/pnas.1606387114.
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