Experimental eye research最新文献

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Phosphoglycerate mutase and methionine synthase act as adhesins of Candida albicans to the corneal epithelium, altering their expression during the tissue adhesion process
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-06 DOI: 10.1016/j.exer.2025.110322
Helena Ordiales , Carlos Olano , Carla Martín , Noelia Blanco-Agudín , Ignacio Alcalde , Jesús Merayo-Lloves , Luis M. Quirós
{"title":"Phosphoglycerate mutase and methionine synthase act as adhesins of Candida albicans to the corneal epithelium, altering their expression during the tissue adhesion process","authors":"Helena Ordiales ,&nbsp;Carlos Olano ,&nbsp;Carla Martín ,&nbsp;Noelia Blanco-Agudín ,&nbsp;Ignacio Alcalde ,&nbsp;Jesús Merayo-Lloves ,&nbsp;Luis M. Quirós","doi":"10.1016/j.exer.2025.110322","DOIUrl":"10.1016/j.exer.2025.110322","url":null,"abstract":"<div><div>The yeast form of <em>Candida albicans</em> uses glycosaminoglycans (GAGs), primarily heparan sulfate, as adhesion receptors for corneal epithelial cells. However, during the transition to the hyphal form, the fungus shifts to using alternative receptors. This study aims to identify fungal adhesins involved in GAG binding and examine their expression dynamics during tissue adhesion.</div><div>Using chromatography, three proteins from the <em>C. albicans</em> cell wall with high affinity for heparin were identified: methionine synthase, phosphoglycerate mutase, and cytochrome <em>c</em>. These proteins were overexpressed in <em>Escherichia coli</em> and tested in adhesion assays. Methionine synthase and phosphoglycerate mutase partially inhibited yeast adhesion to corneal epithelial cells in a concentration-dependent manner, while cytochrome <em>c</em> enhanced adhesion.</div><div>Transcriptional analysis of the genes encoding these proteins (<em>MET6</em>, <em>GMP1</em>, and <em>CYC1</em>), along with other genes related to adhesion and yeast-to-hypha transition (<em>ALS3</em>, <em>HWP1</em>, and <em>INT1</em>), revealed that exposure to exosomes or GAGs increased <em>GMP1</em>, <em>CYC1</em>, and <em>ALS3</em> expression, while reducing <em>HWP1</em> and <em>INT1</em>. In contrast, direct contact with epithelial cells decreased <em>MET6</em> and <em>GMP1</em> expression, but increased <em>HWP1</em> expression.</div><div>These results suggest that methionine synthase and phosphoglycerate mutase act as adhesins for GAGs, with their expression modulated by GAG or exosome interaction to promote adhesion. However, epithelial cell contact alters the expression of adhesins and molecules linked to hyphal formation, highlighting their dynamic role in corneal adhesion.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110322"},"PeriodicalIF":3.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rutin resists Aspergillus fumigatus keratitis by activating Nrf2/HO-1 pathway, inhibiting Dectin-1/p-Syk pathway and affecting fungal structures
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-05 DOI: 10.1016/j.exer.2025.110323
Yuqi Li , Xue Tian , Lina Zhang, Jing Lin, Qian Wang, Lingwen Gu, Hong Li, Bing Yu, Ziyi Wang, Menghui Chi, Guiqiu Zhao, Cui Li
{"title":"Rutin resists Aspergillus fumigatus keratitis by activating Nrf2/HO-1 pathway, inhibiting Dectin-1/p-Syk pathway and affecting fungal structures","authors":"Yuqi Li ,&nbsp;Xue Tian ,&nbsp;Lina Zhang,&nbsp;Jing Lin,&nbsp;Qian Wang,&nbsp;Lingwen Gu,&nbsp;Hong Li,&nbsp;Bing Yu,&nbsp;Ziyi Wang,&nbsp;Menghui Chi,&nbsp;Guiqiu Zhao,&nbsp;Cui Li","doi":"10.1016/j.exer.2025.110323","DOIUrl":"10.1016/j.exer.2025.110323","url":null,"abstract":"<div><div>Fungal keratitis (FK) is a severe vision-threatening eye disease. The fungal invasiveness and excessive inflammatory response contribute to corneal tissue damage. Rutin (RT) possesses anti-inflammatory, antimicrobial, antioxidant, and improved wound-healing characteristics. This study aimed to evaluate antifungal, anti-inflammatory, and therapeutic effects of RT in FK. The results showed that RT exerted antifungal effects by inhibiting fungal growth, altering hyphal morphology, destroying biofilm, and disrupting fungal cellular structures. RT exhibited anti-inflammatory benefits by suppressing the Dectin-1/p-Syk pathway, activating the Nrf2/HO-1 pathway, and decreasing the expression of inflammatory factors in vivo and in vitro. RT demonstrated therapeutic effects by reducing clinical scores, fungal load, macrophage recruitment, and neutrophil activity. In conclusion, RT exhibited anti-inflammatory, antifungal, and therapeutic effects in <em>Aspergillus fumigatus</em> keratitis, and has the potential to become a novel therapeutic strategy for FK.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110323"},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Riboflavin-UV crosslinking of the cornea: Wound healing and biomechanics
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-05 DOI: 10.1016/j.exer.2025.110321
Brecken Blackburn , Barbara A.L. Dutra , Bassel Hammoud , Giuliano Scarcelli , William J. Dupps , J.Bradley Randleman , Steven E. Wilson
{"title":"Riboflavin-UV crosslinking of the cornea: Wound healing and biomechanics","authors":"Brecken Blackburn ,&nbsp;Barbara A.L. Dutra ,&nbsp;Bassel Hammoud ,&nbsp;Giuliano Scarcelli ,&nbsp;William J. Dupps ,&nbsp;J.Bradley Randleman ,&nbsp;Steven E. Wilson","doi":"10.1016/j.exer.2025.110321","DOIUrl":"10.1016/j.exer.2025.110321","url":null,"abstract":"<div><div>The corneal wound healing response to Riboflavin-ultraviolet-crosslinking (RIB-UV-CXL) depends on the specific method used in treatment. The predominance of clinical evidence supports the classical “epithelium-off” RIB-UV-CXL method being more effective in halting ectasia progression than various “epithelium-on” methods, where the corneal epithelium is maintained intact. Corneal transparency results from the precise organization of collagen fibrils and extracellular matrix, along with transparent keratocytes. The mild and transient stromal opacity seen after standard RIB-UV-CXL is linked to changes in hydration, cellularity, and matrix composition. As hydration normalizes, opacity arises from the development of corneal fibroblasts and their secretion of disordered extracellular matrix materials including collagens. Over months, as the epithelial basement membrane regenerates, transitioning stromal cells either undergo apoptosis or revert to keratocan-positive keratocytes, restoring stromal transparency. In normal healing after standard RIB-UV-CXL, the stroma is eventually repopulated predominantly by keratocytes without significant persisting fibroblasts, immune cells, or myofibroblasts. Biomechanical studies have extensively explored how CXL strengthens corneal tissue, providing insight into its therapeutic mechanisms. The purpose of this review is to evaluate the wound healing response and biomechanical changes in the cornea following RIB-UV-CXL.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110321"},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Why has evolution selected for the human eye lens to use an extremely high cholesterol content as a protective mechanism against opacification?
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-03 DOI: 10.1016/j.exer.2025.110320
W.K. Subczynski , R.F. Collery , J. Widomska
{"title":"Why has evolution selected for the human eye lens to use an extremely high cholesterol content as a protective mechanism against opacification?","authors":"W.K. Subczynski ,&nbsp;R.F. Collery ,&nbsp;J. Widomska","doi":"10.1016/j.exer.2025.110320","DOIUrl":"10.1016/j.exer.2025.110320","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110320"},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigation and validation of genes associated with endoplasmic reticulum stress in diabetic retinopathy using various machine learning algorithms
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-03 DOI: 10.1016/j.exer.2025.110317
Limin Zheng , Yaodan Cao , Jinqi Hao , Yanqin Yu , Wuyun Lu , Tianqi Guo , Songtao Yuan
{"title":"Investigation and validation of genes associated with endoplasmic reticulum stress in diabetic retinopathy using various machine learning algorithms","authors":"Limin Zheng ,&nbsp;Yaodan Cao ,&nbsp;Jinqi Hao ,&nbsp;Yanqin Yu ,&nbsp;Wuyun Lu ,&nbsp;Tianqi Guo ,&nbsp;Songtao Yuan","doi":"10.1016/j.exer.2025.110317","DOIUrl":"10.1016/j.exer.2025.110317","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic retinopathy (DR) is a common complication of diabetes, with Endoplasmic reticulum stress (ERS) playing a key role in cellular adaptation, injury, or apoptosis, impacting disease pathology. This study aimed to identify early diagnostic markers for personalized DR treatment.</div></div><div><h3>Methods</h3><div>DR and healthy control (HC) samples were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed ERS-related genes (DE-ERSRGs) were identified, and machine learning algorithms were used to pinpoint DR-specific feature DE-ERSRGs (FDE-ERSRGs). Diagnostic accuracy was assessed using ROC curve analysis. Further analyses included differential expression, co-expression, GO functional, KEGG pathway enrichment, and immune cell infiltration profiling in DR.</div></div><div><h3>Results</h3><div>A total of 55 DE-ERSRGs were initially identified, and after further analysis, two key FDE-ERSRGs, SELENOS and heat shock protein family A member 5 (HSPA5), were highlighted due to their robust differential expression patterns between DR and healthy controls. Both genes exhibited high diagnostic potential, with AUC values of 0.792 and 0.799, respectively, indicating their promise as biomarkers for DR. Additionally, we examined the differential and co-expression patterns of DE-ERSRGs between high- and low-expression groups. We investigated the molecular functions and biological pathways associated with DR, analyzed immune cell infiltration differences between DR and HC groups, and assessed their correlation with FDE-ERSRGs.</div></div><div><h3>Conclusions</h3><div>Our findings provide new insights into the molecular mechanisms and metabolic pathways involved in DR, potentially paving the way for the identification of novel diagnostic and immunotherapeutic biomarkers.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110317"},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Constitutive and hypoxia-induced VEGF production by cultured uveal melanocytes and retinal pigment epithelial cells
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-01 DOI: 10.1016/j.exer.2025.110318
Dan-Ning Hu , Ruihua Zhang , Codrin E. Iacob , Andy Yao , Shun-Fa Yang , Chi- Chao Chan , Richard B. Rosen
{"title":"Constitutive and hypoxia-induced VEGF production by cultured uveal melanocytes and retinal pigment epithelial cells","authors":"Dan-Ning Hu ,&nbsp;Ruihua Zhang ,&nbsp;Codrin E. Iacob ,&nbsp;Andy Yao ,&nbsp;Shun-Fa Yang ,&nbsp;Chi- Chao Chan ,&nbsp;Richard B. Rosen","doi":"10.1016/j.exer.2025.110318","DOIUrl":"10.1016/j.exer.2025.110318","url":null,"abstract":"<div><div>Constitutive secretion of VEGF is crucial for maintaining ocular circulation while hypoxia-induced VEGF secretion plays an important role in pathological neovascularization. Previous studies have highlighted the critical function of RPE cells in these situations. The role of uveal melanocytes (UM) in VEGF production, however, has not been well described. The aim of this study was to compare VEGF production from human RPE and UM cell lines obtained in pairs from 3 donors to minimize individual variability in cellular function. Cells were subjected to hypoxia, (1% oxygen environment) or chemical hypoxia (cobalt chloride, CoCl<sub>2</sub>) at different times or dosages, respectively. The effects of these treatments on the cell viability and cell proliferation were tested using MTT and cell counting with trypan blue testing. The production of VEGF and its main upstream factor (hypoxia-inducible factors-1α, HIF-1α) were measured in the conditioned culture medium and cellular extracts, by using ELISA analysis. Additionally, mRNA levels of VEGF and HIF-1α were quantified through real-time PCR analysis. The effects of CoCl<sub>2</sub> on the expression of VEGF and HIF-1α in UM and RPE cells were also examined using flow cytometry. Hypoxia and COCL<sub>2</sub> exposure did not affect cell viability and cell proliferation. This study revealed that the constitutive production of VEGF by RPE cells is significantly greater than from the UM. However, UM demonstrated a more robust response to high hypoxia or chemical hypoxic stimulation compared to RPE cells. The data suggests that while RPE cells play a critical role in constitutive VEGF production under normal conditions, UM may contribute significantly to the pathological increase in VEGF under severe ocular hypoxia. The observation that intraocular injection of CoCl<sub>2</sub> to produce local chemical hypoxia, results in a significant increase of VEGF levels in intraocular fluids and tissues, has not been reported previously. While this model cannot currently test the <em>in vitro</em> results, it may help further our understanding of UM and RPE cells' roles in VEGF production in future studies using more advanced technologies in a well-established <em>in vivo</em> model.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110318"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MicroRNA-106a regulates the apoptosis and oxidative stress of porcine trabecular meshwork cells by targeting FAS
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-01 DOI: 10.1016/j.exer.2025.110313
Junyi Lai , Chen Tan , Yunsheng Qiao , Xinghuai Sun , Junyi Chen
{"title":"MicroRNA-106a regulates the apoptosis and oxidative stress of porcine trabecular meshwork cells by targeting FAS","authors":"Junyi Lai ,&nbsp;Chen Tan ,&nbsp;Yunsheng Qiao ,&nbsp;Xinghuai Sun ,&nbsp;Junyi Chen","doi":"10.1016/j.exer.2025.110313","DOIUrl":"10.1016/j.exer.2025.110313","url":null,"abstract":"<div><div>This study investigates the impact of miR-106a on trabecular meshwork (TM) and its potential molecular mechanism, as TM dysfunction due to decreased cell viability is a major pathological feature of POAG. Primary porcine TM (PTM) cells were isolated and exposed to hyperoxic conditions to induce senescence. Through small RNA sequencing and qPCR verification, miR-106a was downregulated in aging PTM cells. The transfection system overexpressing miR-106a in PTM cells was achieved by polydopamine (PDA)/polyethyleneimine (PEI) nanoparticles (PDA/PEI NPs). Proliferation, apoptosis, and antioxidant capacity of PTM cells under normal and H<sub>2</sub>O<sub>2</sub>-treated conditions were assessed using CCK-8, mitochondrial assays, and reactive oxygen species measurements. As a result, Overexpression of miR-106a boosted PTM cell proliferation, dampened apoptosis, and enhanced capacity of antioxidative stress. Western blots were carried out to detect the expression of target genes of miR-106a. Mechanically, the expression of the two predicted target genes, FAS and CASP10, and genes of FAS-mediated signaling pathway were suppressed under normal and oxidative stress conditions. Dual-luciferase reporter results confirmed a direct binding between miR-106a and FAS. Thus, miR-106a promotes PTM cells’ viability, suppresses apoptosis and enhances antioxidative stress capacity by targeting FAS in PTM cells. Therefore, our study provides a potential therapeutic target in glaucoma.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110313"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic mutation in HSF4 is associated with retinal degeneration in mice
IF 3 2区 医学
Experimental eye research Pub Date : 2025-02-27 DOI: 10.1016/j.exer.2025.110316
Baixue Liu , Youfei Lang , Yujie Li , MingJun Jiang , Mengjiao Xue , Xiaolin Jia , Xuyan Peng , Yanzhong Hu
{"title":"Genetic mutation in HSF4 is associated with retinal degeneration in mice","authors":"Baixue Liu ,&nbsp;Youfei Lang ,&nbsp;Yujie Li ,&nbsp;MingJun Jiang ,&nbsp;Mengjiao Xue ,&nbsp;Xiaolin Jia ,&nbsp;Xuyan Peng ,&nbsp;Yanzhong Hu","doi":"10.1016/j.exer.2025.110316","DOIUrl":"10.1016/j.exer.2025.110316","url":null,"abstract":"<div><div>Genetic mutations in Hsf4 cause developmental defect of lens at postnatal age. However, the regulatory effect of Hsf4 mutations on retinal homeostasis have not been elucidated. Here we found that HSF4 expresses in retinal and its expression level decrease with age increase. Using Hsf4<sup>del</sup> mice, which express a Hsf4 mutant with deletion of 42 amino acids in-frame- in the N-terminal hydrophobic region and develop cataracts at P27, we found that Hsf4<sup>del</sup> mutation downregulated the expression of visual cycle regulatory proteins, RPE65, RDH5 and RLBP1 and heat shock proteins HSP25 and HSP90, but upregulated retinal gliosis and senescence-associated proteins such as cycle-inhibitors P21 and P16 in P10 retina without change retinal structure. With age increase Hsf4<sup>del</sup> mice undergo retinal degeneration, characterized by thinner ONL, disorganized INL, disconnected RPE, neovascularization, and lipofuscin deposits. ERG results showed that the amplitudes of a- and b-waves at dark adaption were reduced in Hsf4<sup>del</sup> mice at P15, worsening with age. Intravitreal injection of AAV-Flag-Hsf4b in one-month-old Hsf4<sup>del</sup> mice partially restored the expression of visual cycle proteins and ERG responses and reduced the gliosis. Studies in vitro indicated that Hsf4 is able to bind to promoters of RPE65 and RDH5. Altogether, these data suggest that Hsf4 participates in regulating the expression of retinal visual cycle-regulatory proteins in addition to heat shock proteins during early retinal development. Genetic mutations in Hsf4 is associated with not only congenital cataracts but also retinal degeneration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110316"},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PDZK1 regulated by miR-145-5p protects against endothelial cell apoptosis and diabetic retinopathy by targeting mitochondrial function
IF 3 2区 医学
Experimental eye research Pub Date : 2025-02-26 DOI: 10.1016/j.exer.2025.110314
Meixia An , Jialuo Huang , Jian Zhao , Lili Wang , Yanli Liu
{"title":"PDZK1 regulated by miR-145-5p protects against endothelial cell apoptosis and diabetic retinopathy by targeting mitochondrial function","authors":"Meixia An ,&nbsp;Jialuo Huang ,&nbsp;Jian Zhao ,&nbsp;Lili Wang ,&nbsp;Yanli Liu","doi":"10.1016/j.exer.2025.110314","DOIUrl":"10.1016/j.exer.2025.110314","url":null,"abstract":"<div><div>Mitochondria are a focus of biomedical research because of their role in apoptosis and diabetic retinopathy (DR) initiation and progression. However, the detailed mechanisms underlying mitochondrial disorders and endothelial dysfunction during DR remain elusive. We identified PDZ domain containing 1 (PDZK1) as a key factor linking endothelial mitochondrial dysfunction and cell apoptosis during DR progression. PDZK1 was downregulated by high concentrations of glucose in human retinal capillary endothelial cells (HRCECs) and decreased in serum from patients with DR. PDZK1 knockout induced endothelial cell apoptosis and an irregular and disordered arrangement of retinal cells, aggravating DR. Moreover, PDZK1 loss impaired endothelial mitochondrial function with accumulated damaged mitochondria, decreased mitochondrial DNA (mtDNA) content, and increased reactive oxygen species (ROS) production. Mechanistically, mRNA sequencing showed that PDZK1 deficiency in endothelial cells interfered with mitochondrial function by increasing ATF4 (Activating Transcription Factor 4) expression. Further studies showed that PDZK1 was inhibited by miR-145-5p. The expression of miR-145-5p was significantly upregulated in the serum of patients with DR and HRCECs with high glucose concentration, leading to endothelial dysfunction and DR progression. Our results suggested that PDZK1 deficiency is crucial in mediating retinal endothelial cell apoptosis and is associated with mitochondrial dysfunction. PDZK1 overexpression by upstream miRNA, or its downstream molecule, ATF4, may represent novel therapeutic approaches for DR treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110314"},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolomics unveils the role of pipecolic acid in regulating monocytes/macrophages-endothelial cells crosstalk to modulate choroidal neovascularization 代谢组学揭示了哌泊醇酸在调节单核细胞/巨噬细胞-内皮细胞串联以调节脉络膜新生血管中的作用。
IF 3 2区 医学
Experimental eye research Pub Date : 2025-02-26 DOI: 10.1016/j.exer.2025.110315
Chang Liu , Fangcheng Xu , Ruoyan Wei , Yun Cheng , Yunzhe Wang , Yefei Shi , Ke Yang , Wenhui Peng , Weixia Jian , Haixiang Wu , Meiyan Li
{"title":"Metabolomics unveils the role of pipecolic acid in regulating monocytes/macrophages-endothelial cells crosstalk to modulate choroidal neovascularization","authors":"Chang Liu ,&nbsp;Fangcheng Xu ,&nbsp;Ruoyan Wei ,&nbsp;Yun Cheng ,&nbsp;Yunzhe Wang ,&nbsp;Yefei Shi ,&nbsp;Ke Yang ,&nbsp;Wenhui Peng ,&nbsp;Weixia Jian ,&nbsp;Haixiang Wu ,&nbsp;Meiyan Li","doi":"10.1016/j.exer.2025.110315","DOIUrl":"10.1016/j.exer.2025.110315","url":null,"abstract":"<div><div>Choroidal neovascularization (CNV) is a leading cause of vision loss in ocular diseases, including age-related macular degeneration (AMD). Despite extensive research, the underlying mechanisms of CNV remain incompletely understood, with a predominant focus on endothelial dysfunction. CNV, however, is a multi-cellular, multi-stage process involving complex interactions between endothelial cells, monocytes/macrophages, and other immune cells. In this study, we employed a dual-platform metabolomics approach combining liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to identify key metabolic alterations associated with CNV. Our results revealed significant changes in metabolic pathways during CNV progression. Using a myeloid lineage tracing mouse model, we further explored how Pipecolic acid regulates interactions between monocytes/macrophages and endothelial cells, key players in CNV development. We found that Pipecolic acid modulates monocyte/macrophage-endothelial cell crosstalk, inhibiting pathological angiogenesis. These results provide valuable insights into the molecular mechanisms driving CNV and highlight potential therapeutic targets for treating ocular neovascular diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110315"},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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