MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells DOI Creative Commons
Shuhua Fu,

Mei-Chen Lai,

Yunyao Zheng

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(7)

Published: July 15, 2021

The dysregulated microRNAs (miRNAs) are involved in diabetic retinopathy progression. Epithelial mesenchymal transition (EMT) and cell permeability important events retinopathy. However, the function mechanism of miR-195 EMT remain largely unclear. Diabetic models were established using streptozotocin (STZ)-induced mice high glucose (HG)-stimulated ARPE-19 cells. Retina injury was investigated by hematoxylin-eosin (HE) staining. analyzed western blotting, immunofluorescence, wound healing, FITC-dextran assays. MiR-195 expression detected via qRT-PCR. YY1, VEGFA, Snail1, Smurf2 levels blotting. interaction relationship ChIP, Co-IP, or dual-luciferase reporter assay. retina injury, EMT, induced STZ-induced mice. HG MiR-195, Snail1 enhanced, but abundance reduced HG-stimulated VEGFA knockdown decreased attenuated HG-induced permeability. YY1 silence expression, mitigated could bind with it degraded Smurf2-mediated ubiquitination. upregulated to decrease inhibited targeted Smurf2, increased promoted promotes cells increasing VEGFA/Snail1 inhibiting ubiquitination YY1.

Language: Английский

Polymer- and lipid-based nanocarriers for ocular drug delivery: Current status and future perspectives DOI Creative Commons

Haijie Han,

Su Li, Mingyu Xu

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 196, P. 114770 - 114770

Published: March 7, 2023

Ocular diseases seriously affect patients' vision and life quality, with a global morbidity of over 43 million blindness. However, efficient drug delivery to treat ocular diseases, particularly intraocular disorders, remains huge challenge due multiple barriers that significantly the ultimate therapeutic efficacy drugs. Recent advances in nanocarrier technology offer promising opportunity overcome these by providing enhanced penetration, increased retention, improved solubility, reduced toxicity, prolonged release, targeted loaded eyes. This review primarily provides an overview progress contemporary applications nanocarriers, mainly polymer- lipid-based treating various eye highlighting their value achieving delivery. Additionally, covers administration routes, as well prospective future developments challenges field nanocarriers for diseases.

Language: Английский

Citations

151
Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy DOI Creative Commons
Caiying Liu, Wan Sun, Tong Zhu

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 52, P. 102292 - 102292

Published: March 18, 2022

Diabetic retinopathy (DR) is one of the leading causes blindness in world, and timely prevention treatment are very important. Previously, we found that a neurodegenerative factor, Glia maturation factor-β (GMFB), was upregulated vitreous at early stage diabetes, which may play an important role pathogenesis. Here, high glucose environment, large amounts GMFB protein can be secreted vitreous, translocates ATPase ATP6V1A from lysosome, preventing its assembly alkalinizing lysosome retinal pigment epithelial (RPE) cells. ACSL4 recognized by HSC70, receptor for chaperone-mediated autophagy, finally digested lysosome. Abnormalities autophagy-lysosome degradation process lead to accumulation, catalyzes production lethal lipid species induces ferroptosis RPE antibody, activator NKH477, CMA QX77, inhibitor Liproxstatin-1 were all effective diabetic maintaining normal visual function, has powerful clinical application value. Our research broadens understanding relationship between autophagy provides new therapeutic target DR.

Language: Английский

Citations

93
Retinal Cell Damage in Diabetic Retinopathy DOI Creative Commons
Jing Zhou,

Bo Chen

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1342 - 1342

Published: May 8, 2023

Diabetic retinopathy (DR), the most common microvascular complication that occurs in diabetes mellitus (DM), is leading cause of vision loss working-age adults. The prevalence diabetic approximately 30% population and untreated DR can eventually blindness. For decades, was considered a clinically staged by its vascular manifestations. In recent years, emerging evidence has shown causes early neuronal dysfunction neurodegeneration may precede pathology affect retinal neurons as well glial cells. This knowledge leads to new therapeutic strategies aiming prevent at stage DR. Early detection timely treatment protect are critical preventing visual review provides an overview structural functional changes associated with DR, discusses degeneration during retinopathy, mechanisms underlying complications, perspectives on current future clinic therapies.

Language: Английский

Citations

47
AI-based monitoring of retinal fluid in disease activity and under therapy DOI Creative Commons
Ursula Schmidt‐Erfurth, Gregor S. Reiter, Sophie Riedl

et al.

Progress in Retinal and Eye Research, Journal Year: 2021, Volume and Issue: 86, P. 100972 - 100972

Published: June 22, 2021

Retinal fluid as the major biomarker in exudative macular disease is accurately visualized by high-resolution three-dimensional optical coherence tomography (OCT), which used world-wide a diagnostic gold standard largely replacing clinical examination. Artificial intelligence (AI) with its capability to objectively identify, localize and quantify introduces fully automated tools into OCT imaging for personalized management. Deep learning performance has already proven superior human experts, including physicians certified readers, terms of accuracy speed. Reproducible measurement retinal relies on precise AI-based segmentation methods that assign label each voxel denoting type such intraretinal (IRF) subretinal (SRF) or pigment epithelial detachment (PED) location within central 1-, 3- 6-mm area. Such reliable analysis most relevant reflect differences pathophysiological mechanisms impacts function, dynamics resolution during therapy different regimens substances. Yet, an in-depth understanding mode action supervised unsupervised learning, functionality convolutional neural net (CNN) various network architectures needed. Greater insight regarding adequate performance, validation assessment, device- scanning-pattern-dependent variations necessary empower ophthalmologists become qualified AI users. Fluid/function correlation can lead better definition valid variables optimal outcomes individual population level. opens way precision medicine real-world practice leading diseases modern times.

Language: Английский

Citations

66
Contribution of Müller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation DOI Creative Commons
Raul Carpi-Santos, Ricardo Augusto de Melo Reis, Flávia Carvalho Alcântara Gomes

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(4), P. 617 - 617

Published: March 23, 2022

Diabetic retinopathy is a neurovascular complication of diabetes and the main cause vision loss in adults. Glial cells have key role maintenance central nervous system homeostasis. In retina, predominant element Müller cell, specialized cell with radial morphology that spans all retinal layers influences function entire circuitry. provide metabolic support, regulation extracellular composition, synaptic activity control, structural organization blood-retina barrier, antioxidant activity, trophic among other roles. Therefore, impairments actions lead to malfunctions. Accordingly, increasing evidence indicates are affected diabetic may contribute severity disease. Here, we will survey recently described alterations functions cellular events retinopathy, especially related oxidative stress inflammation. This review sheds light on as potential therapeutic targets this

Language: Английский

Citations

60
Diabetic retinopathy: Involved cells, biomarkers, and treatments DOI Creative Commons

Jiahui Ren,

Shuxia Zhang,

Yunfeng Pan

et al.

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

Published: Aug. 9, 2022

Diabetic retinopathy (DR), a leading cause of vision loss and blindness worldwide, is caused by retinal neurovascular unit dysfunction, its cellular pathology involves at least nine kinds cells, including photoreceptors, horizontal bipolar amacrine ganglion glial cells (Müller astrocytes, microglia), endothelial pericytes, pigment epithelial cells. Its mechanism complicated inflammatory factor production, neovascularization, BRB impairment. However, the has not been completely elucidated. Drug treatment for DR gradually advancing recently. Research on potential drug targets relies upon clear information pathogenesis effective biomarkers. Therefore, we reviewed recent literature diagnostic prognostic biomarkers in terms blood, protein, clinical preclinical therapy (including synthesized molecules natural molecules). This review may provide theoretical basis further research.

Language: Английский

Citations

56
Oxidative Stress-Involved Mitophagy of Retinal Pigment Epithelium and Retinal Degenerative Diseases DOI Creative Commons

Si‐Ming Zhang,

Bin Fan, Yu- Lin Li

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3265 - 3276

Published: July 1, 2023

The retinal pigment epithelium (RPE) is a highly specialized and polarized epithelial cell layer that plays an important role in sustaining the structural functional integrity of photoreceptors. However, death RPE common pathological feature various diseases, especially age-related macular degeneration (AMD) diabetic retinopathy (DR). Mitophagy, as programmed self-degradation dysfunctional mitochondria, crucial for maintaining cellular homeostasis survival under stress. contains high density mitochondria necessary it to meet energy demands, so severe stimuli can cause mitochondrial dysfunction excess generation intracellular reactive oxygen species (ROS), which further trigger oxidative stress-involved mitophagy. In this review, we summarize classical pathways mitophagy investigate its progression aiming provide new therapeutic strategy treating degenerative diseases. AMD DR. AMD, excessive ROS production promotes by activating Nrf2/p62 pathway, while DR, may suppress FOXO3-PINK1/parkin signaling pathway or TXNIP-mitochondria-lysosome-mediated

Language: Английский

Citations

39
Mesenchymal stem cell exosomes as nanotherapeutics for dry age-related macular degeneration DOI
Yue Tang,

Yueyue Kang,

Xinru Zhang

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 357, P. 356 - 370

Published: April 10, 2023

Language: Английский

Citations

33
Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation DOI Open Access
Xudong Wang, Tianxi Wang,

Enton Lam

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12090 - 12090

Published: July 28, 2023

The eye is an immune privileged tissue that insulates the visual system from local and systemic provocation to preserve homeostatic functions of highly specialized retinal neural cells. If privilege breached, stimuli will invade subsequently trigger acute inflammatory responses. Local resident microglia become active release numerous immunological factors protect integrity Although responses are necessary control eradicate insults eye, chronic inflammation can cause damage cell dysfunction, leading ocular disease vision loss. In this review, we summarized features in retina key responses, factors, intracellular pathways activated when fails, as well a highlight recent clinical research advances immunity vascular diseases including retinopathy prematurity, age-related macular degeneration, diabetic retinopathy.

Language: Английский

Citations

24
Ocular microvascular complications in diabetic retinopathy: insights from machine learning DOI Creative Commons

Thiara S Ahmed,

Janika Shah,

Yvonne N B Zhen

et al.

BMJ Open Diabetes Research & Care, Journal Year: 2024, Volume and Issue: 12(1), P. e003758 - e003758

Published: Jan. 1, 2024

Introduction Diabetic retinopathy (DR) is a leading cause of preventable blindness among working-age adults, primarily driven by ocular microvascular complications from chronic hyperglycemia. Comprehending the complex relationship between changes in eye and disease progression poses challenges, traditional methods assuming linear or logistical relationships may not adequately capture intricate interactions these advances. Hence, aim this study was to evaluate involvement diabetes mellitus (DM) non-proliferative DR with implementation non-parametric machine learning methods. Research design We conducted retrospective cohort that included optical coherence tomography angiography (OCTA) images collected healthy group (196 eyes), DM no (120 mild (71 moderate (66 eyes). implemented method for four classification tasks used parameters extracted OCTA as predictors: versus healthy, DR, any DR. SHapley Additive exPlanations values were determine importance classification. Results found large choriocapillaris flow deficits most important became less eyes The superficial microvasculature tasks, but task—the stage when deep plays an role. Foveal avascular zone metric general affected, its increased worsening Conclusions findings provide valuable insights into facilitating development early detection intervention strategies.

Language: Английский

Citations

12