Corneal infection (microbial keratitis; MK) is most frequently caused by Pseudomonas aeruginosa, which can utilize an array of secreted virulence factors for pathogenesis. Invasive strains of P. aeruginosa possessing the exoS gene, invade mammalian cells, while cytotoxic strains with the exoU gene rapidly kill host cells. This study investigated the presence of the type six secretion system (T6SS) effector genes in exoU and exoS strains isolated from MK. Fourteen different T6SS effector genes within 20 exoU and 19 exoS P. aeruginosa were explored using whole genome sequence data by BLAST search. To confirm the BLAST search result, PCR was used to detect exoU, exoS and those genes significantly different in the BLAST search, in a separate set of 56 MK isolates from India (24) and Australia (32). The phospholipase D (PLD) activity was measured using the Amplex Red Phospholipase D Assay kit. Three effector genes, tse7, tle1, and pldA, were differentially possessed in the exoU and exoS strains in the BLAST search (p < 0.05). When combining the BLAST search and PCR results, pldA was significantly more common in exoU (81.8%) than the exoS strains (37.3%) (p < 0.01) and trends were similar in Indian (81% exoU vs 45.5% exoS) and Australian (82.6% exoU vs 23% exoS) isolates. PldA expression was associated with detectable PLD activity. Irrespective of geographical region, pldA was more commonly found in exoU P. aeruginosa. While MK due to exoU is generally more severe than those due to exoS, the association between expression of pldA and its function requires further investigation.
角膜感染(微生物角膜炎;MK)最常见的是由铜绿假单胞菌引起的,它可以利用一系列分泌的毒力因子来致病。带有exoS基因的铜绿假单胞菌侵袭性菌株侵入哺乳动物细胞,而带有exoU基因的细胞毒菌株则能迅速杀死宿主细胞。本研究对MK分离株exoU和exoS中6型分泌系统(T6SS)效应基因的存在进行了研究,利用BLAST搜索方法,在20株exoU和19株exoS中发现了14个不同的T6SS效应基因。为了证实BLAST搜索结果,我们在来自印度(24)和澳大利亚(32)的56株MK分离株中使用PCR检测exoU、exoS和BLAST搜索中显著不同的基因。采用Amplex Red phospholipase D Assay kit测定磷脂酶D (PLD)活性。在BLAST搜索中,exoU和exoS菌株中存在三个不同的效应基因,即tse7、tle1和pldA
{"title":"Differential possession of type 6 secretion system effector genes in exoU and exoS Pseudomonas aeruginosa in microbial keratitis","authors":"Tanzina Akter , Abrar Maswood Haider , Fiona Stapleton , Mark Willcox","doi":"10.1016/j.exer.2026.110868","DOIUrl":"10.1016/j.exer.2026.110868","url":null,"abstract":"<div><div>Corneal infection (microbial keratitis; MK) is most frequently caused by <em>Pseudomonas aeruginosa,</em> which can utilize an array of secreted virulence factors for pathogenesis. Invasive strains of <em>P. aeruginosa</em> possessing the <em>exoS</em> gene, invade mammalian cells, while cytotoxic strains with the <em>exoU</em> gene rapidly kill host cells. This study investigated the presence of the type six secretion system (T6SS) effector genes in <em>exoU</em> and <em>exoS</em> strains isolated from MK. Fourteen different T6SS effector genes within 20 <em>exoU</em> and 19 <em>exoS P. aeruginosa</em> were explored using whole genome sequence data by BLAST search. To confirm the BLAST search result, PCR was used to detect <em>exoU, exoS</em> and those genes significantly different in the BLAST search, in a separate set of 56 MK isolates from India (24) and Australia (32). The phospholipase D (PLD) activity was measured using the Amplex Red Phospholipase D Assay kit. Three effector genes, <em>tse7</em>, <em>tle1</em>, and <em>pldA,</em> were differentially possessed in the <em>exoU</em> and <em>exoS</em> strains in the BLAST search (<em>p</em> < 0.05). When combining the BLAST search and PCR results, <em>pldA</em> was significantly more common in <em>exoU</em> (81.8%) than the <em>exoS</em> strains (37.3%) (<em>p</em> < 0.01) and trends were similar in Indian (81% <em>exoU</em> vs 45.5% <em>exoS</em>) and Australian (82.6% <em>exoU</em> vs 23% <em>exoS)</em> isolates. <em>PldA</em> expression was associated with detectable PLD activity. Irrespective of geographical region, <em>pldA</em> was more commonly found in <em>exoU P. aeruginosa.</em> While MK due to <em>exoU</em> is generally more severe than those due to <em>exoS</em>, the association between expression of <em>pldA</em> and its function requires further investigation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110868"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997777","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}
Pub Date : 2026-04-01Epub Date: 2026-01-24DOI: 10.1016/j.exer.2026.110881
Zhaoying Cai , Zhiyang Wang , Ying Zhu , Na Li , Mo Wang , Bei Du , Ruihua Wei
Myopia is the most prevalent eye disease globally with currently no safe and accessible treatments available. Bone morphogenetic protein 2 (BMP2) is located in multiple eye tissues and is crucial for eye development and differentiation. Nonetheless, the precise roles of BMP2 in myopia still unclear. In this investigation, we observed a marked decrease in scleral BMP2 levels in form-deprivation myopia (FDM) guinea pigs. Subconjunctival injections of exogenous BMP2 recombinant protein could partially counteract the decline in choroidal blood perfusion (ChBP) and myopia development. Subsequent investigations revealed that BMP2 alleviates the myopia-induced reduction in scleral Collagen type I alpha 1 expression and the elevation of scleral hypoxia-inducible factor-1α (HIF-1α) levels. In an in vitro hypoxia model, the inhibition of peroxisome proliferator-activated receptor γ (PPARγ) counteracts the influence of BMP2 on scleral extracellular matrix (ECM) remodeling in human scleral fibroblasts. In conclusion, our findings demonstrate that BMP2 inhibits myopia development and regulates scleral ECM remodeling through the enhancement of PPARγ, highlighting BMP2 as a viable and easily obtainable candidate for myopia management.
近视是全球最普遍的眼病,目前尚无安全、可获得的治疗方法。骨形态发生蛋白2 (Bone morphogenetic protein 2, BMP2)存在于多种眼部组织中,对眼部发育和分化至关重要。尽管如此,BMP2在近视中的确切作用仍不清楚。在这项研究中,我们观察到形态剥夺性近视(FDM)豚鼠巩膜BMP2水平显著下降。结膜下注射外源性BMP2重组蛋白可以部分抵消脉络膜血灌注(ChBP)下降和近视的发展。随后的研究发现,BMP2减轻了近视引起的巩膜I型胶原α 1表达的降低和巩膜缺氧诱导因子-1α (HIF-1α)水平的升高。在体外缺氧模型中,过氧化物酶体增殖物激活受体γ (PPARγ)的抑制抵消了BMP2对人巩膜成纤维细胞巩膜细胞外基质(ECM)重塑的影响。总之,我们的研究结果表明,BMP2通过增强PPARγ抑制近视发展并调节巩膜ECM重塑,强调BMP2是一种可行且易于获得的近视治疗候选者。
{"title":"BMP2 inhibits myopia progression by upregulating PPARγ in guinea pigs","authors":"Zhaoying Cai , Zhiyang Wang , Ying Zhu , Na Li , Mo Wang , Bei Du , Ruihua Wei","doi":"10.1016/j.exer.2026.110881","DOIUrl":"10.1016/j.exer.2026.110881","url":null,"abstract":"<div><div>Myopia is the most prevalent eye disease globally with currently no safe and accessible treatments available. Bone morphogenetic protein 2 (BMP2) is located in multiple eye tissues and is crucial for eye development and differentiation. Nonetheless, the precise roles of BMP2 in myopia still unclear. In this investigation, we observed a marked decrease in scleral BMP2 levels in form-deprivation myopia (FDM) guinea pigs. Subconjunctival injections of exogenous BMP2 recombinant protein could partially counteract the decline in choroidal blood perfusion (ChBP) and myopia development. Subsequent investigations revealed that BMP2 alleviates the myopia-induced reduction in scleral Collagen type I alpha 1 expression and the elevation of scleral hypoxia-inducible factor-1α (HIF-1α) levels. In an in vitro hypoxia model, the inhibition of peroxisome proliferator-activated receptor γ (PPARγ) counteracts the influence of BMP2 on scleral extracellular matrix (ECM) remodeling in human scleral fibroblasts. In conclusion, our findings demonstrate that BMP2 inhibits myopia development and regulates scleral ECM remodeling through the enhancement of PPARγ, highlighting BMP2 as a viable and easily obtainable candidate for myopia management.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110881"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050595","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}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.exer.2026.110865
Pengfei Li , Rong wang , Xiaoxi Qian , Mengqi Wen , Zihao Yan , Xiao Cheng , Yuxin Dai , Leyu Zhou , Xi Zhu , Wei Chen , Huaijin Guan , Min Ji
Diabetic cataract (DC) represents a predominant cause of vision impairment among individuals with diabetes, characterized by a multifaceted pathogenesis that encompasses immune-mediated mechanisms. Our objective was to utilize multiomic data to investigate the characteristics of immune cells present in diabetic lenses and to elucidate their underlying mechanisms. Single-cell RNA sequencing (scRNA-seq) was employed to identify cell types and their proportions in lens samples from diabetic and normal rats. Tandem mass tag based quantitative proteomics was then used to screen the in-depth immune targets and mechanism of lens pathological. For the analysis of differential proteins, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed in pathway enrichment assays. Anterior segment optical coherence tomography (AS-OCT) can be used to identify hyperreflective points in diabetic cataract patients. Immunofluorescence staining was performed on anterior capsule membranes from age-related cataract (ARC) and DC patients. scRNA-seq identified five cell types, mononuclear phagocytes as a significant immune cell type in the lens, with increased proportions in diabetic rats compared to normal rats. Further, UCell analysis of macrophage subsets showed that pro-inflammatory M1 macrophages increased significantly and anti-inflammatory M2 macrophages decreased. Subsequently, immunofluorescence staining for the immune cell marker protein CD45 and CD11B on the anterior capsule further confirmed a significantly greater presence of immune cells in DC patients than in ARC patients. AS-OCT findings indicate that the hyper-reflective point on the anterior lens capsule in patients with DC is significantly more pronounced compared to those with ARC. Additionally, AS-OCT is utilized to differentiate between the opacity and clear zone of the LFCs in the enrolled DC patients. Proteomics analysis identified 38 differentially expressed proteins in the opacity zone of LFCs compared to the clear zone in DC patients, comprising 17 upregulated and 21 downregulated. Among them, the significantly upregulated protein MIF is an important macrophage chemokine, which may play a crucial regulatory role in mediating lens immunity. GO and KEGG pathway analyses revealed associations with immune regulation and protein ubiquitination pathways, particularly in the activation of lymphocytes and leukocytes, and K63 ubiquitination. Our study provides evidence for the involvement of immune mechanisms, particularly mononuclear phagocytes, in the development of DC. The upregulation of immune regulation and alterations in protein ubiquitination pathways suggest potential therapeutic targets for DC. Further investigation is essential to understand the specific functions of these immune cells and to design targeted therapies.
{"title":"Single-cell transcriptomics combined with spatial proteomics defines phagocytes type-specific immune regulation in diabetic cataract","authors":"Pengfei Li , Rong wang , Xiaoxi Qian , Mengqi Wen , Zihao Yan , Xiao Cheng , Yuxin Dai , Leyu Zhou , Xi Zhu , Wei Chen , Huaijin Guan , Min Ji","doi":"10.1016/j.exer.2026.110865","DOIUrl":"10.1016/j.exer.2026.110865","url":null,"abstract":"<div><div>Diabetic cataract (DC) represents a predominant cause of vision impairment among individuals with diabetes, characterized by a multifaceted pathogenesis that encompasses immune-mediated mechanisms. Our objective was to utilize multiomic data to investigate the characteristics of immune cells present in diabetic lenses and to elucidate their underlying mechanisms. Single-cell RNA sequencing (scRNA-seq) was employed to identify cell types and their proportions in lens samples from diabetic and normal rats. Tandem mass tag based quantitative proteomics was then used to screen the in-depth immune targets and mechanism of lens pathological. For the analysis of differential proteins, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed in pathway enrichment assays. Anterior segment optical coherence tomography (AS-OCT) can be used to identify hyperreflective points in diabetic cataract patients. Immunofluorescence staining was performed on anterior capsule membranes from age-related cataract (ARC) and DC patients. scRNA-seq identified five cell types, mononuclear phagocytes as a significant immune cell type in the lens, with increased proportions in diabetic rats compared to normal rats. Further, UCell analysis of macrophage subsets showed that pro-inflammatory M1 macrophages increased significantly and anti-inflammatory M2 macrophages decreased. Subsequently, immunofluorescence staining for the immune cell marker protein CD45 and CD11B on the anterior capsule further confirmed a significantly greater presence of immune cells in DC patients than in ARC patients. AS-OCT findings indicate that the hyper-reflective point on the anterior lens capsule in patients with DC is significantly more pronounced compared to those with ARC. Additionally, AS-OCT is utilized to differentiate between the opacity and clear zone of the LFCs in the enrolled DC patients. Proteomics analysis identified 38 differentially expressed proteins in the opacity zone of LFCs compared to the clear zone in DC patients, comprising 17 upregulated and 21 downregulated. Among them, the significantly upregulated protein MIF is an important macrophage chemokine, which may play a crucial regulatory role in mediating lens immunity. GO and KEGG pathway analyses revealed associations with immune regulation and protein ubiquitination pathways, particularly in the activation of lymphocytes and leukocytes, and K63 ubiquitination. Our study provides evidence for the involvement of immune mechanisms, particularly mononuclear phagocytes, in the development of DC. The upregulation of immune regulation and alterations in protein ubiquitination pathways suggest potential therapeutic targets for DC. Further investigation is essential to understand the specific functions of these immune cells and to design targeted therapies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110865"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017971","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":"Comment on “Investigation of the biomechanical changes at the iris-lens interface after vitrectomy with silicone oil tamponade: Insights from ultrasound biomicroscopy”","authors":"Kanishka Harariya , Thakur Rohit Singh , Ankita Kalra , Swarupanjali Padhi , Fayaz Ahamed","doi":"10.1016/j.exer.2026.110884","DOIUrl":"10.1016/j.exer.2026.110884","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110884"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097027","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}
Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and a leading cause of vision loss. Circular RNAs (circRNAs) have emerged as promising biomarkers, yet their role in DR remains unclear. In this study, peripheral blood mononuclear cells (PBMCs) and aqueous humor samples from patients with diabetes mellitus and DR were analyzed by circRNA microarray, with candidate transcripts validated by real-time quantitative PCR. Receiver operating characteristic analysis was performed to assess diagnostic performance. Functional assays using human retinal microvascular endothelial cells (hRMECs), together with bioinformatic prediction and experimental validation, were employed to explore mechanistic pathways. Among the differentially expressed circRNAs, hsa_circ_0053004 was the most significantly upregulated in DR. Its elevated expression was confirmed in both PBMCs and aqueous humor, and gain-of-function studies demonstrated that hsa_circ_0053004 promotes endothelial dysfunction in hRMECs, at least in part through interactions with miR-139-5p and miR-23a-5p. ROC analysis further revealed its strong discriminative capacity between DR and diabetes mellitus. These findings suggest that hsa_circ_0053004 from PBMCs could serve as a potential diagnostic marker for DR and revealed that it is possibly associated with the pathological mechanisms of DR by affecting endothelial dysfunction.
{"title":"Elevated expression of hsa_circ_0053004 in peripheral blood mononuclear cells correlates with endothelial dysfunction in diabetic retinopathy","authors":"Xixi Zhang , Jiahui Jiang , Ying Chen , Juntao Zhang , Jinglin Zhu , Zai-Long Chi , Yufei Wu , Qinkang Lu","doi":"10.1016/j.exer.2026.110880","DOIUrl":"10.1016/j.exer.2026.110880","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus and a leading cause of vision loss. Circular RNAs (circRNAs) have emerged as promising biomarkers, yet their role in DR remains unclear. In this study, peripheral blood mononuclear cells (PBMCs) and aqueous humor samples from patients with diabetes mellitus and DR were analyzed by circRNA microarray, with candidate transcripts validated by real-time quantitative PCR. Receiver operating characteristic analysis was performed to assess diagnostic performance. Functional assays using human retinal microvascular endothelial cells (hRMECs), together with bioinformatic prediction and experimental validation, were employed to explore mechanistic pathways. Among the differentially expressed circRNAs, hsa_circ_0053004 was the most significantly upregulated in DR. Its elevated expression was confirmed in both PBMCs and aqueous humor, and gain-of-function studies demonstrated that hsa_circ_0053004 promotes endothelial dysfunction in hRMECs, at least in part through interactions with miR-139-5p and miR-23a-5p. ROC analysis further revealed its strong discriminative capacity between DR and diabetes mellitus. These findings suggest that hsa_circ_0053004 from PBMCs could serve as a potential diagnostic marker for DR and revealed that it is possibly associated with the pathological mechanisms of DR by affecting endothelial dysfunction.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110880"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040785","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}
Pub Date : 2026-04-01Epub Date: 2026-01-16DOI: 10.1016/j.exer.2026.110870
Ellen Townes-Anderson , Éva Halász , Ilene Sugino , Amy L. Davidow , Luke Fritzky , Fawad A.K. Yousufzai , Marco Zarbin
Using the powerful technique of stimulated emission depletion (STED) confocal microscopy in combination with 3D imaging, we describe the degeneration of cone and rod synapses after one week of retinal detachment in a porcine model. Synaptic invaginations are lost, ribbons change size and shape, and bipolar dendrites sprout. Spontaneous reattachment after hours up to 2 days after detachment appears to restore cone pedicles but does not repair rod spherules one week later. Disjunction of rod synapses remains, both at the point of initial detachment and in areas that were not detached. Moreover, electroretinographic recording of photopic and scotopic b-waves and the flicker response demonstrate that synaptic function of both cone and rod cells remains impaired, even though a-wave function has returned to baseline. The beneficial effects of subretinal injection of the Rho kinase (ROCK) inhibitor AR13503 at the time of detachment, previously shown to reduce injury 2 days after detachment, are now shown to remain for one week. Structural and functional synaptic degeneration is significantly reduced for both cone and rod photoreceptors with ROCK inhibition.
The persistence of synaptic injury after these relatively small detachments that is followed by rapid reattachment indicates the vulnerability of photoreceptor synapses to injury, in part due to increased Rho signaling. Further, the data suggest that visual dysfunction seen in patients after detachment and otherwise successful reattachment can be a result of synaptopathy. Finally, the results reinforce the potential for ROCK inhibition to reduce injury due to iatrogenic detachment in procedures such as gene therapy.
{"title":"Synaptopathy in cone and rod cells after retinal detachment and reattachment","authors":"Ellen Townes-Anderson , Éva Halász , Ilene Sugino , Amy L. Davidow , Luke Fritzky , Fawad A.K. Yousufzai , Marco Zarbin","doi":"10.1016/j.exer.2026.110870","DOIUrl":"10.1016/j.exer.2026.110870","url":null,"abstract":"<div><div>Using the powerful technique of stimulated emission depletion (STED) confocal microscopy in combination with 3D imaging, we describe the degeneration of cone and rod synapses after one week of retinal detachment in a porcine model. Synaptic invaginations are lost, ribbons change size and shape, and bipolar dendrites sprout. Spontaneous reattachment after hours up to 2 days after detachment appears to restore cone pedicles but does not repair rod spherules one week later. Disjunction of rod synapses remains, both at the point of initial detachment and in areas that were not detached. Moreover, electroretinographic recording of photopic and scotopic b-waves and the flicker response demonstrate that synaptic function of both cone and rod cells remains impaired, even though a-wave function has returned to baseline. The beneficial effects of subretinal injection of the Rho kinase (ROCK) inhibitor AR13503 at the time of detachment, previously shown to reduce injury 2 days after detachment, are now shown to remain for one week. Structural and functional synaptic degeneration is significantly reduced for both cone and rod photoreceptors with ROCK inhibition.</div><div>The persistence of synaptic injury after these relatively small detachments that is followed by rapid reattachment indicates the vulnerability of photoreceptor synapses to injury, in part due to increased Rho signaling. Further, the data suggest that visual dysfunction seen in patients after detachment and otherwise successful reattachment can be a result of synaptopathy. Finally, the results reinforce the potential for ROCK inhibition to reduce injury due to iatrogenic detachment in procedures such as gene therapy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110870"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997697","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}
Pub Date : 2026-04-01Epub Date: 2026-02-03DOI: 10.1016/j.exer.2026.110901
Xiaofang Wang , Zhiyuan Zhang , Huihui Wu , Yinru Wang , Mengru Su , Xinghong Sun
The objective of this study was to explore the lipid metabolic changes in the active thyroid-associated ophthalmopathy (TAO) through tear lipidomics analysis, screen for biomarkers related to disease activity, and analyze their correlation with clinical features. The study included 32 patients with active TAO and 30 patients with inactive TAO. Liquid chromatography-mass spectrometry (LC-MS) was used to perform lipidomics analysis on tear samples to identify differential lipid molecules. Multivariate statistical analyses, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were conducted, and machine learning algorithms were employed to evaluate the predictive ability of lipid biomarkers. Additionally, clinical characteristics and blood indicators of the patients were collected to analyze their correlation with the lipid biomarkers. The study identified 247 significantly different lipids in the tears of patients with active TAO, of which 104 were upregulated, mainly involving sphingolipids, glycerophospholipids, and glycerolipids. Through machine learning, four lipids (BisMePA(36:6e), MGMG(38:0), PC(38:3), SM(d38:1)) were selected, which showed good predictive ability for TAO activity (AUC >0.8 for all). Moreover, these lipids were significantly correlated with blood lipid indicators, exophthalmos degree, Schirmer I test, and the area of the foveal avascular zone (FAZ) of the retina. This tear lipidomics analysis provides a new approach for screening biomarkers in the active phase of TAO. The identified lipid biomarkers are significantly correlated with clinical features and have potential clinical application value.
{"title":"Predictive value of tear lipidomics biomarkers for TAO activity and relationship with clinical characteristics","authors":"Xiaofang Wang , Zhiyuan Zhang , Huihui Wu , Yinru Wang , Mengru Su , Xinghong Sun","doi":"10.1016/j.exer.2026.110901","DOIUrl":"10.1016/j.exer.2026.110901","url":null,"abstract":"<div><div>The objective of this study was to explore the lipid metabolic changes in the active thyroid-associated ophthalmopathy (TAO) through tear lipidomics analysis, screen for biomarkers related to disease activity, and analyze their correlation with clinical features. The study included 32 patients with active TAO and 30 patients with inactive TAO. Liquid chromatography-mass spectrometry (LC-MS) was used to perform lipidomics analysis on tear samples to identify differential lipid molecules. Multivariate statistical analyses, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were conducted, and machine learning algorithms were employed to evaluate the predictive ability of lipid biomarkers. Additionally, clinical characteristics and blood indicators of the patients were collected to analyze their correlation with the lipid biomarkers. The study identified 247 significantly different lipids in the tears of patients with active TAO, of which 104 were upregulated, mainly involving sphingolipids, glycerophospholipids, and glycerolipids. Through machine learning, four lipids (BisMePA(36:6e), MGMG(38:0), PC(38:3), SM(d38:1)) were selected, which showed good predictive ability for TAO activity (AUC >0.8 for all). Moreover, these lipids were significantly correlated with blood lipid indicators, exophthalmos degree, Schirmer I test, and the area of the foveal avascular zone (FAZ) of the retina. This tear lipidomics analysis provides a new approach for screening biomarkers in the active phase of TAO. The identified lipid biomarkers are significantly correlated with clinical features and have potential clinical application value.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110901"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124320","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}
Pub Date : 2026-04-01Epub Date: 2026-01-27DOI: 10.1016/j.exer.2026.110892
Ke Liu , Wang-yang Xu , Ruiqing Fu , Yiwen Wang
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. While aberrant DNA methylation may contribute, a genome-wide profile in trabecular meshwork (TM) is lacking. This study performed reduced-representation bisulfite sequencing (RRBS) on TM samples from 42 POAG patients and 20 non-glaucomatous controls, identifying 8885 significant differentially methylated CpG sites (DMCs) and 3148 differentially methylated regions (DMRs), revealing a pronounced hypomethylation pattern in POAG. Hypomethylated genes were associated with ossification, collagen fibril organization, and the RhoA/ROCK signaling, whereas hypermethylated genes were enriched in androgen receptor signaling, the NABA core matrisome, and actin filament processes—collectively highlighting extracellular matrix (ECM) dysregulation as a central theme. Integrated methylome-transcriptome analysis identified four high-priority genes (COL5A1, COL5A2, JAM3, and HTRA1) among hypomethylated-upregulated candidates, implicating them in pathogenic ECM remodeling in POAG. This study presents the first RRBS-based methylome profile of POAG, revealing significant epigenetic alterations in pathways and genes related to TM dysfunction. These findings enhance our understanding of the molecular mechanisms underlying POAG and may inform future therapeutic strategies.
{"title":"Methylome profiling reveals epigenetic alterations in the trabecular meshwork of primary open-angle glaucoma","authors":"Ke Liu , Wang-yang Xu , Ruiqing Fu , Yiwen Wang","doi":"10.1016/j.exer.2026.110892","DOIUrl":"10.1016/j.exer.2026.110892","url":null,"abstract":"<div><div>Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. While aberrant DNA methylation may contribute, a genome-wide profile in trabecular meshwork (TM) is lacking. This study performed reduced-representation bisulfite sequencing (RRBS) on TM samples from 42 POAG patients and 20 non-glaucomatous controls, identifying 8885 significant differentially methylated CpG sites (DMCs) and 3148 differentially methylated regions (DMRs), revealing a pronounced hypomethylation pattern in POAG. Hypomethylated genes were associated with ossification, collagen fibril organization, and the RhoA/ROCK signaling, whereas hypermethylated genes were enriched in androgen receptor signaling, the NABA core matrisome, and actin filament processes—collectively highlighting extracellular matrix (ECM) dysregulation as a central theme. Integrated methylome-transcriptome analysis identified four high-priority genes (<em>COL5A1</em>, <em>COL5A2</em>, <em>JAM3</em>, and <em>HTRA1</em>) among hypomethylated-upregulated candidates, implicating them in pathogenic ECM remodeling in POAG. This study presents the first RRBS-based methylome profile of POAG, revealing significant epigenetic alterations in pathways and genes related to TM dysfunction. These findings enhance our understanding of the molecular mechanisms underlying POAG and may inform future therapeutic strategies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110892"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085174","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}
Pub Date : 2026-04-01Epub Date: 2026-02-04DOI: 10.1016/j.exer.2026.110904
Ute Mathis , Gustav Christensen , Marita Feldkaemper , Falk Schroedl , Alexandra Kaser-Eichberger , Frank Schaeffel
Purpose
Changes in choroidal thickness are currently used to predict future refractive error development but there is incomplete knowledge about the communication between choroid and sclera. We studied how choroidal thickness changes interact with scleral thickness changes and how the abundance of dopamine (DA)- and all-trans retinoic acid (atRA)-synthetizing choroidal cells varies when choroidal thickness is altered by drugs.
Methods
Changes in choroidal thickness were induced by a single intravitreal injection in the morning of the muscarinic antagonist atropine, the DA agonist apomorphine or the DA antagonist spiperone. Thickness of the choroid and the scleral layers was measured by spectral domain optical coherence tomography (SD-OCT). Immunocytochemistry was used to study the distribution of dopamine-synthetizing structures in the choroid and their colocalisation with retinaldehyde dehydrogenase 2 (RADLH2), the key synthetizing enzyme of atRA.
Results
(1) Both atropine and apomorphine increased choroidal thickness over the day while spiperone resulted in a decrease. (2) For apomorphine and spiperone, choroidal thickness changes were positively correlated with thickness changes in both the cartilaginous and fibrous layers of the sclera. With atropine, only the cartilaginous layer thickened. (3) DA was co-localized with RALDH2 in stromal cells in the choroid in a few cases but the numbers of double-stained cells increased massively after drug injections. (4) RALDH2-immunoreactivity (indicating atRA activity) increased, no matter whether the choroid and the sclera thickened or thinned.
Conclusions
Following drug injections, thickness changes of choroid and sclera were correlated and occurred without phase delay. Numbers of DA and RALDH2 co-expressing cells in the choroid increased. Choroidal dopaminergic cells that synthesize atRA appear to act as activators of scleral metabolic activity during both scleral growth stimulation and inhibition.
{"title":"Interactions of choroid and sclera in the myopia model of the chicken","authors":"Ute Mathis , Gustav Christensen , Marita Feldkaemper , Falk Schroedl , Alexandra Kaser-Eichberger , Frank Schaeffel","doi":"10.1016/j.exer.2026.110904","DOIUrl":"10.1016/j.exer.2026.110904","url":null,"abstract":"<div><h3>Purpose</h3><div>Changes in choroidal thickness are currently used to predict future refractive error development but there is incomplete knowledge about the communication between choroid and sclera. We studied how choroidal thickness changes interact with scleral thickness changes and how the abundance of dopamine (DA)- and all-trans retinoic acid (atRA)-synthetizing choroidal cells varies when choroidal thickness is altered by drugs.</div></div><div><h3>Methods</h3><div>Changes in choroidal thickness were induced by a single intravitreal injection in the morning of the muscarinic antagonist atropine, the DA agonist apomorphine or the DA antagonist spiperone. Thickness of the choroid and the scleral layers was measured by spectral domain optical coherence tomography (SD-OCT). Immunocytochemistry was used to study the distribution of dopamine-synthetizing structures in the choroid and their colocalisation with retinaldehyde dehydrogenase 2 (RADLH2), the key synthetizing enzyme of atRA.</div></div><div><h3>Results</h3><div>(1) Both atropine and apomorphine increased choroidal thickness over the day while spiperone resulted in a decrease. (2) For apomorphine and spiperone, choroidal thickness changes were positively correlated with thickness changes in both the cartilaginous and fibrous layers of the sclera. With atropine, only the cartilaginous layer thickened. (3) DA was co-localized with RALDH2 in stromal cells in the choroid in a few cases but the numbers of double-stained cells increased massively after drug injections. (4) RALDH2-immunoreactivity (indicating atRA activity) increased, no matter whether the choroid and the sclera thickened or thinned.</div></div><div><h3>Conclusions</h3><div>Following drug injections, thickness changes of choroid and sclera were correlated and occurred without phase delay. Numbers of DA and RALDH2 co-expressing cells in the choroid increased. Choroidal dopaminergic cells that synthesize atRA appear to act as activators of scleral metabolic activity during both scleral growth stimulation and inhibition.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110904"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131646","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}
Pub Date : 2026-04-01Epub Date: 2026-01-10DOI: 10.1016/j.exer.2026.110858
Toqa Yasser Shakour , Ahmad A. Othman , Iman A. Fahmy , Ahmed Yousef Amin Ali , Asmaa M. Eid , Eman S. El-Wakil , Hager S. Zoghroban
Acanthamoeba keratitis (AK) is a serious sight-threatening infection caused by various species of the opportunistic protozoan Acanthamoeba, especially in contact lens wearers and immunocompromised people. The aim of the study was to assess the therapeutic efficacy of two topical nitazoxanide (NTZ) formulations in experimentally induced AK. Three groups of male New Zealand white rabbits were used: group (A): infected and received NTZ in suspension form; group (B): infected and received NTZ in liquid crystal forming system; and group (C): infected and received topical chlorhexidine 0.02 %. The right eyes of the animals served as their corresponding infected untreated control. The animals were infected by Acanthamoeba isolated from human cases of AK. The effects of treatment were assessed over 30 days through daily clinical evaluation; grading of AK; and parasitological and histopathological examination of corneal tissues. The present work revealed that after inducing keratitis, signs of infection appeared on day 3, and all groups showed similar infection rates before treatment began. Corneal opacity improved significantly in animals treated by NTZ liquid crystal form, especially by days 18–30 post-treatment, scoring therapeutic outcomes comparable or superior to the chlorhexidine-treated group and markedly better than the NTZ suspension-treated group. Histopathological assessment confirmed these findings, with the NTZ liquid crystal group exhibiting minimal inflammation and no detectable cysts, highlighting its potential as an effective alternative agent against Acanthamoeba. In conclusion, NTZ in its liquid crystal form showed promise as a potential therapy for AK. Further studies are needed to establish safety and efficacy of topical NTZ in humans and its possible use in combination with other amoebicidal agents.
{"title":"Therapeutic efficacy of nitazoxanide on Acanthamoeba keratitis in an experimental model","authors":"Toqa Yasser Shakour , Ahmad A. Othman , Iman A. Fahmy , Ahmed Yousef Amin Ali , Asmaa M. Eid , Eman S. El-Wakil , Hager S. Zoghroban","doi":"10.1016/j.exer.2026.110858","DOIUrl":"10.1016/j.exer.2026.110858","url":null,"abstract":"<div><div><em>Acanthamoeba</em> keratitis (AK) is a serious sight-threatening infection caused by various species of the opportunistic protozoan <em>Acanthamoeba</em>, especially in contact lens wearers and immunocompromised people. The aim of the study was to assess the therapeutic efficacy of two topical nitazoxanide (NTZ) formulations in experimentally induced AK. Three groups of male New Zealand white rabbits were used: group (A): infected and received NTZ in suspension form; group (B): infected and received NTZ in liquid crystal forming system; and group (C): infected and received topical chlorhexidine 0.02 %. The right eyes of the animals served as their corresponding infected untreated control. The animals were infected by <em>Acanthamoeba</em> isolated from human cases of AK. The effects of treatment were assessed over 30 days through daily clinical evaluation; grading of AK; and parasitological and histopathological examination of corneal tissues. The present work revealed that after inducing keratitis, signs of infection appeared on day 3, and all groups showed similar infection rates before treatment began. Corneal opacity improved significantly in animals treated by NTZ liquid crystal form, especially by days 18–30 post-treatment, scoring therapeutic outcomes comparable or superior to the chlorhexidine-treated group and markedly better than the NTZ suspension-treated group. Histopathological assessment confirmed these findings, with the NTZ liquid crystal group exhibiting minimal inflammation and no detectable cysts, highlighting its potential as an effective alternative agent against <em>Acanthamoeba</em>. In conclusion, NTZ in its liquid crystal form showed promise as a potential therapy for AK. Further studies are needed to establish safety and efficacy of topical NTZ in humans and its possible use in combination with other amoebicidal agents.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110858"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959223","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}