Experimental eye research最新文献

{"title":"Sodium-iodate injection can replicate retinal and choroid degeneration in pigmented mice: Using multimodal imaging and label-free quantitative proteomics analysis","authors":"Shijing Wu ,&nbsp;Fang Zheng ,&nbsp;Ailing Sui ,&nbsp;Di Wu ,&nbsp;Zhiqing Chen","doi":"10.1016/j.exer.2024.110050","DOIUrl":"10.1016/j.exer.2024.110050","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO₃), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO₃-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO₃ injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO₃-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110050"},"PeriodicalIF":3.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992990","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}

{"title":"Research on the role of exosomes secreted by immortalized adipose-derived mesenchymal stem cells differentiated into pericytes in the repair of high glucose-induced retinal vascular endothelial cell damage","authors":"Sihui Wu ,&nbsp;Yunnan Zhang ,&nbsp;Yaru Hou ,&nbsp;Jing Zhu ,&nbsp;Hongling Yang ,&nbsp;Yan Cui","doi":"10.1016/j.exer.2024.110046","DOIUrl":"10.1016/j.exer.2024.110046","url":null,"abstract":"<div><p>Diabetic retinopathy, a leading cause of vision impairment, is marked by microvascular complications in the retina, including pericyte loss, a key indicator of early-stage disease. This study explores the therapeutic potential of exosomes derived from immortalized adipose-mesenchymal stem cells differentiated into pericyte-like cells in restoring the function of mouse retinal microvascular endothelial cells damaged by high glucose conditions, thereby contributing to the understanding of early diabetic retinopathy intervention strategies. To induce immortalized adipose-mesenchymal stem cells differentiation into pericyte-like cells, the study employed pericyte growth supplement. And confirmed the success of cell differentiation through the detection of α-smooth muscle actin and neural/glial antigen 2 expression by Western blot and immunofluorescence. Exosomes were isolated from the culture supernatant of immortalized adipose-mesenchymal stem cells using ultracentrifugation and characterized through Western blot for exosomal markers (CD9, CD81, and TSG101), transmission electron microscopy, and nanoparticle tracking analysis. Their influence on mouse retinal microvascular endothelial cells under high glucose stress was assessed through various functional assays. Findings revealed that exosomes, especially those from pericyte-like immortalized adipose-mesenchymal stem cells, were efficiently internalized by retinal microvascular endothelial cells and effectively counteracted high glucose-induced apoptosis. These exosomes also mitigated the rise in reactive oxygen species levels and suppressed the migratory and angiogenic properties of retinal microvascular endothelial cells, as demonstrated by Transwell and tube formation assays, respectively. Furthermore, they preserved endothelial barrier function, reducing hyperglycemia-induced permeability. At the molecular level, qRT-PCR analysis showed that exosome treatment modulated the expression of critical genes involved in angiogenesis (VEGF-A, ANG2, MMP9), inflammation (IL-1β, TNF-α), gap junction communication (CX43), and cytoskeletal regulation (ROCK1), with the most prominent effects seen with exosomes from pericyte-like immortalized adipose-mesenchymal stem cells. High glucose increased the expression of pro-angiogenic and pro-inflammatory markers, which were effectively normalized post-exosome treatment. In conclusion, this research highlights the reparative capacity of exosomes secreted by pericyte-like differentiated immortalized adipose-mesenchymal stem cells in reversing the detrimental effects of high glucose on retinal microvascular endothelial cells. By reducing apoptosis, oxidative stress, inflammation, and abnormal angiogenic behavior, these exosomes present a promising avenue for therapeutic intervention in early diabetic retinopathy. Future studies can focus on elucidating the precise molecular mechanisms and exploring their translational potential in vivo.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110046"},"PeriodicalIF":3.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014483524002677/pdfft?md5=b451b58bca981374d5022c7deea86e0a&pid=1-s2.0-S0014483524002677-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987747","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}

{"title":"CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway","authors":"Hong Yang ,&nbsp;Ru-yi Han ,&nbsp;Ruo-wen Gong ,&nbsp;Ya-juan Zhang ,&nbsp;Shi-shi Yang ,&nbsp;Ge-zhi Xu ,&nbsp;Wei Liu","doi":"10.1016/j.exer.2024.110042","DOIUrl":"10.1016/j.exer.2024.110042","url":null,"abstract":"<div><p>Retinal vascular leakage is a major event in several retinal diseases, including diabetic retinopathy (DR). In a previous study, we demonstrated that the aqueous humor concentration of Cystatin C (CST3), a physiological inhibitor of cysteine protease, is negatively correlated with the severity of diabetic macular edema. However, its function in the retina has not been clearly elucidated. In this study, we found a significant decrease in the aqueous humor concentration of CST3 with DR progression. Furthermore, we found that CST3 was expressed in retinal endothelial cells and that its expression was significantly downregulated in high glucose-treated human retinal microvascular endothelial cells <strong>(</strong>HRMECs) and the retinal vessels of oxygen-induced retinopathy (OIR) mice. Silencing CST3 expression resulted in decreased HRMEC migration and tubule formation ability. Exogenous addition of the CST3 protein significantly improved HRMEC migration and tubular formation. <em>In-vivo</em> experiments demonstrated that CST3 silencing induced retinal vascular leakage in WT mice, while its intravitreal injection significantly reduced retinal leakage in OIR mice. Mechanistically, CST3 promoted the expression of the downstream adhesion molecules, claudin5, VE-cadherin, and ZO-1, in retinal vascular cells by regulating the Rap1 signaling pathway. Therefore, this study revealed a novel mechanism by which CST3 improves retinal vascular function and provided evidence that it is a potential therapeutic target for retinal vascular leakage.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110042"},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987745","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}

{"title":"M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye","authors":"Chao Yang ,&nbsp;Qi Gao ,&nbsp;Jing Liu ,&nbsp;Yan Wu ,&nbsp;Xufeng Hou ,&nbsp;Lijuan Sun ,&nbsp;Xuhui Zhang ,&nbsp;Yao Lu ,&nbsp;Yingxin Yang","doi":"10.1016/j.exer.2024.110041","DOIUrl":"10.1016/j.exer.2024.110041","url":null,"abstract":"<div><p>Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110041"},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987746","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}

{"title":"Inducible RPE-specific GPX4 knockout causes oxidative stress and retinal degeneration with features of age-related macular degeneration","authors":"Alaina M. Wojciechowski,&nbsp;Brent A. Bell,&nbsp;Ying Song,&nbsp;Brandon D. Anderson,&nbsp;Alexa Conomikes,&nbsp;Cecilia Petruconis,&nbsp;Joshua L. Dunaief","doi":"10.1016/j.exer.2024.110028","DOIUrl":"10.1016/j.exer.2024.110028","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. This disease involves oxidative stress burden in the retina leading to death of retinal pigment epithelial (RPE) cells and photoreceptors. The retina is susceptible to oxidative stress, in part due to high metabolic activity and high concentration of polyunsaturated fatty acids that undergo lipid peroxidation chain reactions. Antioxidant enzymes exist in the retina to combat this stress, including glutathione peroxidase 4 (GPX4). GPX4 specifically reduces oxidized lipids, protecting against lipid peroxidation-induced oxidative stress, which is noted in dry AMD. We hypothesize that <em>Gpx4</em> knockout within the RPE will result in an environment of chronic oxidative stress yielding degeneration akin to AMD. C57BL/6J mice with a floxed <em>Gpx4</em> gene were mated with <em>Rpe65Cre/ER</em> mice. Offspring containing <em>Rpe65Cre</em> ± alleles and either <em>Gpx4</em> WT or <em>Gpx4 fl/fl</em> alleles were administered tamoxifen to induce <em>Gpx4</em> knockout in <em>Gpx4 fl/fl</em> mice. At sequential timepoints, retinal phenotypes were assessed via <em>in vivo</em> imaging utilizing confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT), and visual function was probed by electroretinography. Retinas were studied post-mortem by immunohistochemical analyses, electron microscopy, plastic sectioning, and quantitative polymerase chain reaction and Western analyses. The RPE-specific <em>Gpx4</em> knockout model was validated via Western analysis indicating diminished GPX4 protein only within the RPE and not the neural retina. Following <em>Gpx4</em> knockout, RPE cells became dysfunctional and died, with significant cell loss occurring 2 weeks post-knockout. Progressive thinning of the photoreceptor layer followed RPE degeneration and was accompanied by loss of visual function. OCT and light microscopy showed hyperreflective foci and enlarged, pigmented cells in and above the RPE layer. Electron microscopy revealed decreased mitochondrial cristae and loss of basal and apical RPE ultrastructure. Finally, there was increased carboxyethylpyrrole staining, indicating oxidation of docosahexaenoic acid, and increased levels of mRNAs encoding oxidative stress-associated genes in the RPE and photoreceptors. Overall, we show that RPE-localized GPX4 is necessary for the health of the RPE and outer retina, and that knockout recapitulates phenotypes of dry AMD.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110028"},"PeriodicalIF":3.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916486","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}

{"title":"PRMT1 mediates the proliferation of Y79 retinoblastoma cells by regulating the p53/p21/CDC2/cyclin B pathway","authors":"Yanyan Zhang ,&nbsp;Longbing Mao ,&nbsp;Alan Jiang ,&nbsp;Jingchao Liu ,&nbsp;Yongan Lu ,&nbsp;Chunyue Yao ,&nbsp;Guofu Huang","doi":"10.1016/j.exer.2024.110040","DOIUrl":"10.1016/j.exer.2024.110040","url":null,"abstract":"<div><p>Retinoblastoma (RB) is the most common intraocular malignancy among children and presents a certain mortality risk, especially in low- and middle-income countries. Clarifying the molecular mechanisms underlying the onset and progression of retinoblastoma is vital for devising effective cancer treatment approaches. PRMT1, a major type I PRMT, plays significant roles in cancer development. However, its expression and role in retinoblastoma are still unclear. Our research revealed a marked increase in PRMT1 levels in both retinoblastoma tissues and Y79 cells. The overexpression of PRMT1 in Y79 cells promoted their growth and cell cycle progression. Conversely, the suppression of PRMT1 hindered the growth of Y79 cells and impeded cell cycle progression. Mechanistically, PRMT1 mediated the growth of Y79 retinoblastoma cells by targeting the p53/p21/CDC2/Cyclin B pathway. Additionally, the ability of PRMT1 knockdown to suppress cell proliferation was also observed <em>in vivo</em>. Overall, PRMT1 could function as a potential target for therapeutic treatment in individuals with retinoblastoma.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110040"},"PeriodicalIF":3.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970927","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}

{"title":"MicroRNA-based engineered mesenchymal stem cell extracellular vesicles to treat visual deficits after blast-induced trauma","authors":"Yasaman Anvarinia ,&nbsp;Nobel A. Del Mar ,&nbsp;Ahmed M. Awad ,&nbsp;Shahadat Hossain ,&nbsp;Amritha TM. Seetharaman ,&nbsp;Sriram Ravindran ,&nbsp;Steven Roth ,&nbsp;Rajashekhar Gangaraju","doi":"10.1016/j.exer.2024.110031","DOIUrl":"10.1016/j.exer.2024.110031","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Our previous studies have shown the benefit of intravitreal injection of a mesenchymal stem cell (MSC)- derived secretome to treat visual deficits in a mild traumatic brain injury (mTBI) mouse model. In this study, we have addressed whether MSC-derived extracellular vesicles (EV) overexpressing miR424, which particularly targets neuroinflammation, show similar benefits in the mTBI model. Adult C57BL/6 mice were subjected to a 50-psi air pulse on the left side, overlying the forebrain, resulting in mTBI. Sham-blast mice were controls. Within an hour of blast injury, 3 μl (∼7.5 × 10&lt;sup&gt;8&lt;/sup&gt; particles) of miR424-EVs, native-EVs, or saline was delivered intravitreally. One month later, retinal morphology was observed through optical coherence tomography (OCT); visual function was assessed using optokinetic nystagmus (OKN) and electroretinogram (ERG), followed by immunohistological analysis. A separate study in adult mice tested the dose-response of EVs for safety. Blast injury mice with saline showed decreased visual acuity compared with the sham group (0.30 ± 0.03 vs. 0.39 ± 0.01 c/d, p &lt; 0.02), improved with miR424-EVs (0.39 ± 0.02 c/d, p &lt; 0.01) but not native-EVs (0.33 ± 0.04 c/d, p &gt; 0.05). Contrast sensitivity thresholds of blast mice receiving saline increased compared with the sham group (85.3 ± 5.9 vs. 19.9 ± 4.8, %, p &lt; 0.001), rescued by miR424-EVs (23.6 ± 7.3 %, p &lt; 0.001) and native-EVs (45.6 ± 10.7 %, p &lt; 0.01). Blast injury decreased “b” wave amplitude compared to sham mice (94.6 ± 24.0 vs. 279.2 ± 25.3 μV, p &lt; 0.001), improved with miR424-EVs (173.0 ± 27.2 μV, p &lt; 0.03) and native-EVs (230.2 ± 37.2 μV, p &lt; 0.01) with a similar decrease in a-wave amplitude in blast mice improved with both miR424-EVs and native-EVs. Immunohistology showed increased GFAP and IBA1 in blast mice with saline compared with sham (GFAP: 11.9 ± 1.49 vs. 9.1 ± 0.8, mean intensity/100,000 μm&lt;sup&gt;2&lt;/sup&gt; area, p &lt; 0.03; IBA1: 36.08 ± 4.3 vs. 24.0 ± 1.54, mean intensity/100,000 μm&lt;sup&gt;2&lt;/sup&gt; area, p &lt; 0.01), with no changes with native-EVs (GFAP: 12.6 ± 0.79, p &gt; 0.05; IBA1: 32.8 ± 2.9, p &gt; 0.05), and miR424-EV (GFAP: 13.14 ± 0.76, p &gt; 0.05; IBA1: 31.4 ± 2.7, p &gt; 0.05). Both native-EVs and miR424-EVs exhibited vitreous aggregation, as evidenced by particulates in the vitreous by OCT, and increased vascular structures, as evidenced by αSMA and CD31 immunostainings. The number of capillary lumens in the ganglion cell layer increased with increased particles in the eye, with native EVs showing the worst effects. In conclusion, our study highlights the promise of EV-based therapies for treating visual dysfunction caused by mTBI, with miR424-EVs showing particularly strong neuroprotective benefits. Both miR424-EVs and native-EVs provided similar protection, but issues with EV aggregation and astrogliosis or microglial/macrophage activation at the current dosage call for improved delivery methods and dosage adjust","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110031"},"PeriodicalIF":3.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916487","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}

{"title":"Hyperreflective choroidal foci in diabetic eyes with and without macular edema: Novel insights on diabetic choroidopathy","authors":"Giulia Midena ,&nbsp;Luca Danieli ,&nbsp;Elisabetta Pilotto ,&nbsp;Luisa Frizziero ,&nbsp;Edoardo Midena","doi":"10.1016/j.exer.2024.110020","DOIUrl":"10.1016/j.exer.2024.110020","url":null,"abstract":"<div><p>Histopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p &lt; 0.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC &gt;0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm <em>in vivo</em> the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110020"},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912289","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}

{"title":"Lipid profile in the aqueous humor of patients with myopia","authors":"Danyang Che ,&nbsp;Lingfeng Lv ,&nbsp;Yiting Cao ,&nbsp;Yingjie Zhang ,&nbsp;Qi Yu ,&nbsp;Fang Li ,&nbsp;Jibo Zhou","doi":"10.1016/j.exer.2024.110023","DOIUrl":"10.1016/j.exer.2024.110023","url":null,"abstract":"<div><p>We examined the lipid profiles in the aqueous humor (AH) of myopic patients to identify differences and investigate the relationships among dissertating lipids. Additionally, we assessed spherical equivalents and axial lengths to explore the pathogenesis of myopia. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to qualitatively and quantitatively analyze the lipid composition of samples from myopic patients with axial lengths &lt;26 mm (Group A) and &gt;28 mm (Group B). Differences in lipid profiles between the two groups were determined using univariate and multivariate analyses. Receiver operator characteristic (ROC) curves were used to identify discriminating lipids. Spearman correlation analysis explored the associations between lipid concentrations and biometric parameters. Three hundred and nine lipids across 21 lipid classes have been identified in this study. Five lipids showed significant differences between Group B and Group A (VIP &gt;1, P &lt; 0.05): BMP (20:3/22:3), PG (22:1/24:0), PS (14:1/22:4), TG (44:2)_FA18:2, and TG (55:3)_FA18:1. The area under the curve (AUC) for these lipids was &gt;0.75. Notably, the concentrations of BMP (20:3/22:3), PS (14:1/22:4), and TG (55:3)_FA18:1 were correlated with spherical equivalents, while BMP (20:3/22:3) and PS (14:1/22:4) correlated with axial lengths. Our study identified five differential lipids in myopic patients, with three showing significant correlations with the degree of myopia. These findings enhance our understanding of myopia pathogenesis through lipidomic alterations, emphasizing changes in cell membrane composition and function, energy metabolism and storage, and pathways involving inflammation, peroxisome proliferator-activated receptors (PPAR), and metabolic processes related to phosphatidylserine, phosphatidylglycerol, triglycerides, polyunsaturated fatty acids, and cholesterol.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110023"},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912291","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}

{"title":"Necrostatin-1 protects corneal epithelial cells by inhibiting the RIPK1/RIPK3/MLKL cascade in a benzalkonium chloride-induced model of necroptosis","authors":"Xinlin Yan ,&nbsp;Yarong Yan ,&nbsp;Jinghua Liu ,&nbsp;Yapeng Jing ,&nbsp;Peng Hao ,&nbsp;Xi Chen ,&nbsp;Xuan Li","doi":"10.1016/j.exer.2024.110030","DOIUrl":"10.1016/j.exer.2024.110030","url":null,"abstract":"<div><h3>Purpose</h3><p>Benzalkonium chloride (BAC) is commonly used as a preservative in ophthalmic medications, despite its potential to induce chemical injury. Extensive research has demonstrated that BAC can lead to adverse effects, including injuries to the ocular surface. Our study aimed to elucidate the underlying mechanism of necroptosis induced by BAC.</p></div><div><h3>Methods</h3><p>Human corneal epithelial (HCE) cells and mouse corneas were subjected to chemical injury, and the necrostatin-1 (Nec1) group was compared to the dimethylsulfoxide (DMSO) group. The extent of damage to HCE cells was assessed using CCK-8 and flow cytometry. Hematoxylin and eosin staining, as well as fluorescein sodium staining, were used to detect and characterize corneal injury. The activation of inflammatory cytokines and necroptosis-related proteins and genes was evaluated using Western blotting, immunofluorescence staining, and quantitative RT‒PCR.</p></div><div><h3>Results</h3><p>In our study, the induction of necroptosis by a hypertonic solution was not observed. However, necroptosis was observed in HCE cells exposed to NaOH and BAC, which activated the receptor-interacting protein kinase 1 (RIPK1) - receptor-interacting protein kinase 3 (RIPK3) - mixed lineage kinase domain-like protein (MLKL) signaling pathway. In mouse corneal tissues, BAC could induce necroptosis and inflammation. The administration of Nec1 mitigated the inflammatory response and ocular surface damage caused by BAC-induced necroptosis in our experimental models. Furthermore, our in vivo experiments revealed that the severity of necroptosis was greater in the 3-day group than in the 7-day group.</p></div><div><h3>Conclusions</h3><p>Necroptosis plays a role in the pathological development of ocular surface injury caused by exposure to BAC. Furthermore, our study demonstrated that the administration of Nec1 could mitigate the pathological effects of necroptosis induced by BAC in clinical settings.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"247 ","pages":"Article 110030"},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912314","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}