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Differential possession of type 6 secretion system effector genes in exoU and exoS Pseudomonas aeruginosa in microbial keratitis 微生物性角膜炎exoU和exoS铜绿假单胞菌6型分泌系统效应基因的差异
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.exer.2026.110868
Tanzina Akter , Abrar Maswood Haider , Fiona Stapleton , Mark Willcox
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
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引用次数: 0
BMP2 inhibits myopia progression by upregulating PPARγ in guinea pigs BMP2通过上调豚鼠PPARγ抑制近视进展。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-24 DOI: 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。
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引用次数: 0
Single-cell transcriptomics combined with spatial proteomics defines phagocytes type-specific immune regulation in diabetic cataract 单细胞转录组学联合空间蛋白质组学定义糖尿病性白内障吞噬细胞类型特异性免疫调节。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 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.
糖尿病性白内障(DC)是糖尿病患者视力损害的主要原因,其特点是多方面的发病机制,包括免疫介导的机制。我们的目的是利用多组学数据来研究糖尿病晶状体中存在的免疫细胞的特征并阐明其潜在的机制。采用单细胞RNA测序(scRNA-seq)技术鉴定糖尿病大鼠和正常大鼠晶状体样品中的细胞类型和比例。基于串联质量标签的定量蛋白质组学技术,深入筛选晶状体病变的免疫靶点和机制。对于差异蛋白的分析,采用基因本体(GO)和京都基因与基因组百科全书(KEGG)进行途径富集分析。前段光学相干断层扫描(AS-OCT)可用于识别糖尿病性白内障患者的高反射点。对年龄相关性白内障(ARC)和DC患者的前囊膜进行免疫荧光染色。scRNA-seq鉴定出五种细胞类型,单核吞噬细胞是晶状体中重要的免疫细胞类型,与正常大鼠相比,糖尿病大鼠的比例增加。此外,巨噬细胞亚群的UCell分析显示,促炎M1巨噬细胞显著增加,抗炎M2巨噬细胞显著减少。随后,前囊免疫细胞标记蛋白CD45和CD11B的免疫荧光染色进一步证实DC患者中免疫细胞的存在明显高于ARC患者。AS-OCT结果显示,DC患者的前晶状体囊超反射点明显比ARC患者更明显。此外,AS-OCT用于区分入组DC患者lfc的不透明区和清晰区。蛋白质组学分析发现,与DC患者的透明区相比,lfc的不透明区有38个差异表达蛋白,其中17个上调,21个下调。其中,显著上调的蛋白MIF是一种重要的巨噬细胞趋化因子,可能在介导晶状体免疫中发挥重要的调节作用。GO和KEGG通路分析揭示了与免疫调节和蛋白质泛素化通路的关联,特别是在淋巴细胞和白细胞的激活以及K63泛素化中。我们的研究为免疫机制,特别是单核吞噬细胞参与DC的发展提供了证据。免疫调节的上调和蛋白泛素化途径的改变提示了DC的潜在治疗靶点。进一步的研究对于了解这些免疫细胞的特定功能和设计靶向治疗是必不可少的。
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引用次数: 0
Comment on “Investigation of the biomechanical changes at the iris-lens interface after vitrectomy with silicone oil tamponade: Insights from ultrasound biomicroscopy” 超声生物显微观察玻璃体切除术后虹膜-晶状体界面生物力学变化
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 10.1016/j.exer.2026.110884
Kanishka Harariya , Thakur Rohit Singh , Ankita Kalra , Swarupanjali Padhi , Fayaz Ahamed
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引用次数: 0
Elevated expression of hsa_circ_0053004 in peripheral blood mononuclear cells correlates with endothelial dysfunction in diabetic retinopathy Hsa_circ_0053004在糖尿病视网膜病变患者外周血单核细胞中的表达升高与内皮功能障碍相关
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-21 DOI: 10.1016/j.exer.2026.110880
Xixi Zhang , Jiahui Jiang , Ying Chen , Juntao Zhang , Jinglin Zhu , Zai-Long Chi , Yufei Wu , Qinkang Lu
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.
糖尿病视网膜病变(DR)是糖尿病的主要微血管并发症,也是导致视力丧失的主要原因。环状rna (circRNAs)已成为有前景的生物标志物,但它们在DR中的作用尚不清楚。在这项研究中,我们用circRNA芯片分析了糖尿病和DR患者的外周血单个核细胞(PBMCs)和房水样本,并通过实时定量PCR验证了候选转录本。进行受试者工作特征分析以评估诊断表现。利用人视网膜微血管内皮细胞(hRMECs)进行功能分析,结合生物信息学预测和实验验证,探索其机制途径。在差异表达的circRNAs中,hsa_circ_0053004在dr中表达上调最为显著,其表达升高在pbmc和房水中都得到证实,功能获得研究表明,hsa_circ_0053004促进hRMECs的内皮功能障碍,至少部分是通过与miR-139-5p和miR-23a-5p的相互作用。ROC分析进一步显示DR与糖尿病之间有较强的判别能力。这些发现提示pbmc中的hsa_circ_0053004可作为DR的潜在诊断标志物,并揭示其可能通过影响内皮功能障碍与DR的病理机制相关。
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引用次数: 0
Synaptopathy in cone and rod cells after retinal detachment and reattachment 视网膜脱离和再附着后锥体和杆状细胞的突触病变。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 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.
利用强大的刺激发射损耗(STED)共聚焦显微镜技术结合3D成像,我们描述了猪模型视网膜脱离一周后锥体和杆突触的变性。突触内陷消失,带状改变大小和形状,双极树突发芽。在脱离后2天内,数小时内自发再附着似乎可以恢复椎弓根,但一周后不能修复杆状小球体。杆状突触的分离仍然存在,无论是在最初的分离点还是在未分离的区域。此外,视网膜电图记录的光性和暗性b波以及闪烁反应表明,尽管a波功能已经恢复到基线,但锥细胞和杆状细胞的突触功能仍然受损。在脱离时视网膜下注射Rho激酶(ROCK)抑制剂AR13503的有益作用,先前显示在脱离后2天减少损伤,现在显示持续一周。结构和功能突触变性显著减少锥体和杆状光感受器与ROCK抑制。在这些相对较小的分离之后,突触损伤的持续存在,随后是快速的再附着,这表明光感受器突触容易受到损伤,部分原因是Rho信号的增加。此外,数据表明,在脱离或成功再附着的患者中看到的视觉功能障碍可能是突触病的结果。最后,研究结果强化了ROCK抑制在基因治疗等过程中减少医源性脱离造成的损伤的潜力。
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引用次数: 0
Predictive value of tear lipidomics biomarkers for TAO activity and relationship with clinical characteristics 泪脂组学标志物对TAO活性的预测价值及其与临床特征的关系。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 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.
本研究旨在通过泪液脂质组学分析,探讨活动性甲状腺相关眼病(TAO)患者的脂质代谢变化,筛选与疾病活动性相关的生物标志物,并分析其与临床特征的相关性。该研究包括32例活动性TAO患者和30例非活动性TAO患者。采用液相色谱-质谱联用(LC-MS)对泪液样品进行脂质组学分析,鉴别不同的脂质分子。进行多元统计分析,包括主成分分析(PCA)和偏最小二乘判别分析(PLS-DA),并采用机器学习算法评估脂质生物标志物的预测能力。收集患者的临床特征和血液指标,分析其与脂质生物标志物的相关性。本研究发现活跃TAO患者泪液中有247种脂质存在显著差异,其中有104种脂质上调,主要涉及鞘脂、甘油磷脂和甘油脂。通过机器学习筛选出4种脂质(BisMePA(36:6e)、MGMG(38:0)、PC(38:3)、SM(d38:1),对TAO活性具有较好的预测能力(AUC均为>.8)。血脂与血脂指标、眼球突出度、Schirmer I试验、视网膜中央凹无血管区(FAZ)面积有显著相关性。这种泪液脂质组学分析为TAO活动期生物标志物的筛选提供了一种新的方法。所鉴定的脂质生物标志物与临床特征显著相关,具有潜在的临床应用价值。
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引用次数: 0
Methylome profiling reveals epigenetic alterations in the trabecular meshwork of primary open-angle glaucoma 甲基组分析揭示原发性开角型青光眼小梁网的表观遗传改变。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 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.
原发性开角型青光眼(POAG)是世界范围内不可逆失明的主要原因。虽然异常DNA甲基化可能起作用,但缺乏小梁网络(TM)的全基因组谱。本研究对42例POAG患者和20例非青光眼对照的TM样本进行了减少代表性亚硫酸盐测序(RRBS),鉴定出8885个显著差异甲基化CpG位点(DMCs)和3148个差异甲基化区域(DMRs),揭示了POAG中明显的低甲基化模式。低甲基化基因与骨化、胶原纤维组织和RhoA/ROCK信号传导相关,而高甲基化基因则富集于雄激素受体信号传导、NABA核心基质体和肌动蛋白丝过程中,共同突出了细胞外基质(ECM)失调作为中心主题。综合甲基组-转录组分析在低甲基化上调的候选基因中发现了四个高优先级基因(COL5A1, COL5A2, JAM3和HTRA1),这表明它们与POAG致病性ECM重塑有关。这项研究首次提出了基于rrbs的POAG甲基化谱,揭示了与TM功能障碍相关的途径和基因的显著表观遗传改变。这些发现增强了我们对POAG分子机制的理解,并可能为未来的治疗策略提供信息。
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引用次数: 0
Interactions of choroid and sclera in the myopia model of the chicken 鸡近视模型中脉络膜与巩膜的相互作用。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 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.
目的:脉络膜厚度的变化目前被用来预测未来屈光不正的发展,但对脉络膜和巩膜之间的联系尚不完全了解。我们研究了脉络膜厚度变化如何与巩膜厚度变化相互作用,以及当药物改变脉络膜厚度时,合成多巴胺(DA)和全反式维甲酸(atRA)的脉络膜细胞的丰度如何变化。方法:早晨单次玻璃体内注射毒蕈碱拮抗剂阿托品、DA激动剂阿波啡或DA拮抗剂spiperone诱导脉络膜厚度变化。采用光谱域光学相干断层扫描(SD-OCT)测量脉络膜和巩膜层厚度。利用免疫细胞化学方法研究了多巴胺合成结构在脉络膜中的分布及其与atRA合成关键酶视黄醛脱氢酶2 (RADLH2)的共定位。结果:(1)阿托品和阿波啡均使脉络膜厚度增加,而螺泼酮使脉络膜厚度减少。(2)阿扑啡和spiperone的巩膜厚度变化与巩膜软骨层和纤维层厚度变化均呈正相关。使用阿托品,只有软骨层增厚。(3)少数病例中DA与RALDH2在脉络膜基质细胞中共定位,但注射药物后双染细胞数量大量增加。(4)无论脉络膜和巩膜增厚或变薄,raldh2免疫反应性(表明atRA活性)均升高。结论:药物注射后脉络膜与巩膜厚度变化具有相关性,且无相延迟。脉络膜中DA和RALDH2共表达细胞数量增加。合成atRA的脉络膜多巴胺能细胞似乎在巩膜生长刺激和抑制过程中作为巩膜代谢活性的激活剂。
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引用次数: 0
Therapeutic efficacy of nitazoxanide on Acanthamoeba keratitis in an experimental model nitazoxanide治疗棘阿米巴角膜炎的实验模型。
IF 2.7 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-10 DOI: 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.
棘阿米巴角膜炎(AK)是一种由棘阿米巴原虫引起的严重感染,特别是在隐形眼镜佩戴者和免疫功能低下的人群中。目的是评价两种硝唑尼特(NTZ)制剂治疗实验性AK的疗效。将雄性新西兰大白兔31只分为7组:A-s组感染后给予NTZ悬浮液;组(A-c):前一组的对照组;B-s组:感染并给药NTZ液晶形成系统;B-c组:前两组的对照组;C-s组:感染后外用0.02%氯己定;组(C-c):前一组的对照组;组(D):正常对照组。通过日常临床评价、AK评分、角膜组织寄生虫学和组织病理学检查,在30天内评估治疗效果。本研究发现,在诱导角膜炎后,在第3天出现感染迹象,并且所有组在治疗开始前的感染率相似。NTZ液晶形态处理组角膜混浊明显改善,特别是在第18 ~ 30天,其结果与氯己定处理组相当或优于,明显优于NTZ混悬液处理组。组织病理学分析证实了这些发现,NTZ液晶组表现出最小的炎症和未检测到的囊肿,突出了其作为AK有效替代治疗的潜力。
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Experimental eye research
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