Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy DOI Creative Commons
Qiaoyun Gong, Haiyan Wang, Ping Yu

et al.

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: March 25, 2021

Autophagy is a self-degradative pathway involving intracellular substance degradation and recycling. Recently, this process has attracted great deal of attention for its fundamental effect on physiological processes in cells, tissues, the maintenance organismal homeostasis. Dysregulation autophagy occurs some diseases, including immune disease, cancer, neurodegenerative conditions. Diabetic retinopathy (DR), as serious microvascular complication diabetes, main cause visual loss working-age adults worldwide. The pathogenic mechanisms DR are thought to be associated with accumulation oxidative stress, retinal cell apoptosis, inflammatory response, endoplasmic reticulum (ER) nutrient starvation. These factors closely related regulation under pathological Increasing evidence demonstrated potential role progression through different pathways. However, date not understood, whether altered level flux protects DR, or instead aggravates progression, needs explored. In review, we explore alterations functions cells tissues conditions, explain involved progression. We aim provide basis which stress-modulated may suggest novel targets future therapeutic intervention DR.

Language: Английский

Emerging role of extracellular vesicles in diabetic retinopathy DOI Creative Commons
Junyan Zhu, Jin Huang, Yaoxiang Sun

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(4), P. 1631 - 1646

Published: Jan. 1, 2024

Diabetic retinopathy (DR), a complex complication of diabetes mellitus (DM), is leading cause adult blindness.Hyperglycemia triggers DR, resulting in microvascular damage, glial apoptosis, and neuronal degeneration.Inflammation oxidative stress play crucial roles during this process.Current clinical treatments for DR primarily target the advanced retinal disorder but offer limited benefits with inevitable side effects.Extracellular vesicles (EVs) exhibit unique morphological features, contents, biological properties can be found cell culture supernatants, various body fluids, tissues.In EVs specific cargo composition would induce reaction receptor once internalized, mediating cellular communication disease progression.Increasing evidence indicates that monitoring changes EV quantity content aid diagnosis prognosis.Furthermore, extensive research investigating potential these nanoparticles as effective therapeutic agents preclinical models DR.This review explores current understanding pathological effects development, discusses their biomarkers strategies, paves way further advancements.

Language: Английский

Citations

10
KIF11 UFMylation Maintains Photoreceptor Cilium Integrity and Retinal Homeostasis DOI
Jie Ran,

Guizhi Guo,

Sai Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(25)

Published: April 26, 2024

Abstract The photoreceptor cilium is vital for maintaining the structure and function of retina. However, molecular mechanisms underlying integrity retinal homeostasis are largely unknown. Herein, it shown that kinesin family member 11 (KIF11) localizes at transition zone (connecting cilium) plays a crucial role in orchestrating integrity. KIF11 depletion causes malformations both ciliary axoneme membranous discs, resulting degeneration accumulation drusen‐like deposits throughout Mechanistic studies show stability regulated by an interplay between its UFMylation ubiquitination; lysine 953 inhibits ubiquitination synoviolin 1 thereby prevents proteasomal degradation. 953‐to‐arginine mutant more stable than wild‐type also effective reversing defects induced depletion. These findings identify critical maintenance homeostasis.

Language: Английский

Citations

10
Copper metabolism and its role in diabetic complications: A review DOI Creative Commons

Dongkai Jia,

Lulu Liu, Wei Liu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107264 - 107264

Published: June 12, 2024

Disturbances in copper (Cu) homeostasis have been observed diabetes and associated complications. Cu is an essential micronutrient that plays important roles various fundamental biological processes. For example, diabetic cardiomyopathy with elevated levels of the serum tissues. Therefore, targeting may be a novel treatment strategy for This review provides overview physiological metabolism homeostasis, followed by discussion disorders during occurrence progression Finally, we discuss recent therapeutic advances use coordination complexes as treatments complications their potential mechanisms action. contributes to complete understanding role demonstrates broad application prospects Cu-coordinated compounds agents.

Language: Английский

Citations

9
Photoreceptor metabolic window unveils eye–body interactions DOI Creative Commons
Shaopeng Yang,

Zhuoyao Xin,

Weijing Cheng

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 15, 2025

Language: Английский

Citations

1
Sodium Iodate-Induced Ferroptosis in Photoreceptor-Derived 661W Cells Through the Depletion of GSH DOI Open Access
Chao Chen, Han Wang,

Jiuyu Yang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2334 - 2334

Published: March 5, 2025

Oxidative stress-induced photoreceptor cell death is closely associated with the etiology of age-related macular degeneration (AMD), and sodium iodate (SI) has been widely used as an oxidant stimulus in AMD models to induce retinal pigment epithelium (RPE) death. However, mechanism underlying SI-induced remains controversial unclear. In this study, we elucidate that ferroptosis a critical form induced by SI photoreceptor-derived 661W cells. disrupts system Xc-, leading glutathione (GSH) depletion triggering lipid peroxidation, thereby promoting Additionally, enhances intracellular Fe2+ levels, which further facilitates reactive oxygen species (ROS) accumulation, making cells more susceptible ferroptosis. Exogenous GSH, well specific inhibitors such Fer-1 antioxidants like NAC, significantly attenuate These findings provide new insights into mechanisms key pathway

Language: Английский

Citations

1
Clinical electroretinography in diabetic retinopathy: a review DOI
J. Jason McAnany,

Oksana Persidina,

Jason C. Park

et al.

Survey of Ophthalmology, Journal Year: 2021, Volume and Issue: 67(3), P. 712 - 722

Published: Sept. 4, 2021

Language: Английский

Citations

48
Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy DOI Creative Commons
Rafael Simó, Olga Simó‐Servat, Patricia Bogdanov

et al.

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(8), P. 1320 - 1320

Published: Aug. 23, 2021

The concept of diabetic retinopathy as a microvascular disease has evolved and is now considered more complex complication in which neurovascular unit impairment plays an essential role and, therefore, can be main therapeutic target the early stages disease. However, neurodegeneration not always apparent primary event natural story retinopathy, phenotyping characterization recommendable to identify those patients whom neuroprotective treatment might benefit. In recent years, myriad treatments based on neuroprotection have been tested experimental models, but interestingly, there are drugs with dual activity (neuroprotective vasculotropic). this review, evidence concerning approaches targeting will presented, along critical review scientific gaps problems remain overcome before our knowledge transferred clinical practice.

Language: Английский

Citations

45
Gut Microbiota Composition and Fecal Metabolic Profiling in Patients With Diabetic Retinopathy DOI Creative Commons

Zixi Zhou,

Zheng Zheng,

Xiaojing Xiong

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Oct. 15, 2021

Recent evidence suggests there is a link between metabolic diseases and gut microbiota. To investigate the microbiota composition fecal phenotype in diabetic retinopathy (DR) patients. DNA was extracted from 50 samples (21 individuals with type 2 diabetes mellitus-associated (DR), 14 mellitus but without (DM) 15 sex- age-matched healthy controls) then sequenced by high-throughput 16S rDNA analysis. Liquid chromatography mass spectrometry (LC-MS)-based metabolomics simultaneously performed on samples. A significant difference observed DR groups DM groups. At genus level, Faecalibacterium , Roseburia Lachnospira Romboutsia were enriched patients compared to individuals, while Akkermansia depleted. Compared those patient group, five genera, including Prevotella enriched, Bacillus Veillonella Pantoea depleted Fecal metabolites significantly differed population The levels of carnosine, succinate, nicotinic acid niacinamide lower than controls. patients, nine six KEGG annotation revealed 17 pathways differentially abundant controls, only two identified namely, arginine-proline α-linolenic pathways. In correlation analysis, armillaramide found be negatively associated Subdoligranulum positively . Traumatic correlated Our study differential compositions characteristic phenotypes Additionally, relevant. We speculated that may cause alterations metabolites, which contribute disease progression, providing new direction for understanding DR.

Language: Английский

Citations

44
Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy DOI Creative Commons
Xiaohui Du, Le Yang, Ling Kong

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 27, 2022

Diabetic retinopathy (DR) is a universal microvascular complication of diabetes mellitus (DM), which the main reason for global sight damage/loss in middle-aged and/or older people. Current clinical analyses, like hemoglobin A1c, possess some importance as prognostic indicators DR severity, but no effective circulating biomarkers are used clinic currently, and studies on latent pathophysiology remain lacking. Recent developments omics, especially metabolomics, continue to disclose novel potential several fields, including not limited DR. Therefore, based overview we reviewed progress analytical technology prominent roles current status DR, update various DR-related samples via tear well vitreous humor, aqueous retina, plasma, serum, cerebrospinal fluid, urine, feces. In this review, underscored in-depth analysis elucidation common different biological integrated results, namely, alanine, lactate, glutamine. Alanine may participate regulate glucose metabolism through stimulating N-methyl-D-aspartate receptors subsequently suppressing insulin secretion, pathogenesis Abnormal lactate could cause extensive oxidative stress neuroinflammation, eventually leading retinal hypoxia metabolic dysfunction; other hand, high-level damage structure function endothelial cell barrier G protein-coupled receptor 81. glutamine indicates disturbance glutamate recycling, affect activation Müller cells proliferation PPP1CA–YAP–GS–Gln–mTORC1 pathway.

Language: Английский

Citations

35
Acteoside inhibits high glucose-induced oxidative stress injury in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway DOI Creative Commons

Jingfei Yang,

Zhijuan Hua,

Zhikun Zheng

et al.

Experimental Eye Research, Journal Year: 2023, Volume and Issue: 232, P. 109496 - 109496

Published: May 31, 2023

Diabetes retinopathy (DR) is one of the most common microvascular complications diabetes. Retinal pigment epithelial (RPE) cells exposed to a high glucose environment experience series functional damages, which an important factor in promoting progression DR. Acteoside (ACT) has strong antioxidant and anti-apoptotic properties, but mechanism ACT DR not completely clear. Therefore, purpose present study was explore whether inhibits damage RPE through antioxidative effects alleviate process. The vitro cell model constructed by treating with glucose, vivo animal injecting streptozotocin (STZ) into peritoneal cavity mice induce proliferation apoptosis were detected CCK-8 flow cytometry assays, respectively. expression changes Nrf2, Keap1, NQO1 HO-1 evaluated qRT‒PCR, Western blot immunohistochemistry analyses. MDA, SOD, GSH-Px T-AOC contents kits. ROS nuclear translocation Nrf2 observed immunofluorescence assays. HE staining used measure thickness outer layer (ONL) retina, TUNEL detect number apoptotic retinas mice. In study, effectively ameliorated retina diabetic (HG)-induced cells, treatment had following effects: improved proliferation, decreased apoptosis, inhibited Keap1 expression, promoted upregulated (the target genes Nrf2) concentration, increased levels indicators. However, knockdown reversed above phenomena, indicated that protective function HG-induced are closely related Nrf2. summary, demonstrated oxidative stress injury Keap1/Nrf2/ARE pathway.

Language: Английский

Citations

18