Ocular Surface最新文献_第10页

Pipeline: Therapeutics – Two views of off-label use 管道：治疗学-超说明书使用的两种观点

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-10 DOI: 10.1016/j.jtos.2025.04.005

Gary D. Novack

引用次数: 0

Acanthamoeba keratitis treatment outcomes compared for drug delivery by protocol versus physician's individualised treatment 棘阿米巴角膜炎的治疗结果比较方案给药与医生个体化治疗。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-07 DOI: 10.1016/j.jtos.2025.03.008

John K.G. Dart , Vincenzo Papa , Paolo Rama , Karl Anders Knutsson , Saj Ahmad , Scott Hau , Sara Sanchez , Antonella Franch , Federica Birattari , Pia Leon , Adriano Fasolo , Ewa Mrukwa-Kominek , Katarzyna Jadczyk-Sorek , Fiona Carley , Hossain Parwez , Darwin C. Minassian

Purpose

To compare Acanthamoeba keratitis (AK) outcomes for treatment delivered using a detailed protocol versus physician's individualised treatment.

Methods

This double cohort study compared the outcomes of these different delivery methods for PHMB 0.02 % and diamidine 0.1 % dual therapy. The primary outcome was the medical cure rate without surgery within 12 months (MCR_12) and the secondary was visual acuity. Any change of treatment, any surgery, or treatment for >12 months was a failure. Outcomes were both unadjusted and adjusted, using multivariable analysis, for baseline differences affecting outcomes. Patients were from two centres in Milan and London treated at different times; the individualised cohort (1991–2012) and per-protocol cohort (2017–2021).

Results

The individualised cohort included 96 and the per-protocol 47 patients. Both unadjusted and adjusted results were similar. The unadjusted outcomes for both centres combined showed significantly improved outcomes for per-protocol treatment with a 1.59-fold improvement in MCR_12 (95 % CI 1.40–1.80, p < 0.001) and a 2.1-fold increase in visual acuity ≥20/25 (95 % CI 1.34–3.29, p < 0.001). Amongst potential confounding factors examined, neither baseline AK disease stage, treatment centre nor the type of diamidine significantly influenced outcomes.

Conclusions

This study shows significant advantages for the use of protocol delivered versus individualised treatment for AK. The use of evidence-based treatment delivery protocols, like the one used here for AK, might improve outcomes for all causes of microbial keratitis and could offer practitioners and patients the benefit of having an easy-to-follow drug delivery protocol, with known outcomes.

目的：比较棘阿米巴角膜炎（AK）的治疗结果提供了一个详细的方案和医生的个体化治疗。方法：本双队列研究比较了0.02% PHMB和0.1%二胺双重治疗的不同给药方式的结果。主要观察指标为12个月内不手术治愈率（MCR_12），次要观察指标为视力。任何治疗方法的改变，任何手术，或长达12个月的治疗都是失败的。采用多变量分析，对影响结果的基线差异进行了未调整和调整。来自米兰和伦敦两个中心的患者在不同时间接受治疗；个体化队列（1991-2012）和按方案队列（2017-2021）。结果：个体化队列96例，按方案47例。未调整和调整后的结果相似。两个中心未经调整的合并结果显示，按方案治疗的结果显著改善，MCR_12改善1.59倍（95% CI 1.40 - 1.80, p < 0.001），视力≥20/25增加2.1倍（95% CI 1.34 - 3.29, p < 0.001）。在检查的潜在混杂因素中，基线AK疾病分期、治疗中心和二胺类型均未显著影响结果。结论：这项研究显示了使用方案传递与个性化治疗AK的显著优势。使用循证治疗方案，如这里使用的AK，可能会改善所有原因的微生物角膜炎的结果，并可以为医生和患者提供一个易于遵循的药物给药方案，已知的结果。

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引用次数: 0

Expert consensus on pediatric dry eye: Insights from a European Delphi study 专家对儿童干眼症的共识：来自欧洲德尔菲研究的见解

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-05 DOI: 10.1016/j.jtos.2025.04.004

Edoardo Villani , Paolo Nucci , Jose Manuel Benitez-del-Castillo , Annegret Dahlmann-Noor , Wolf Alexander Lagrèze , Dominique Bremond-Gignac , PeDED Delphi Group

Context

Dry Eye Disease (DED) is a symptomatic multifactorial condition of the ocular surface, primarily characterized by tear film instability, which can lead to ocular surface damage. While traditionally associated with adults, recent studies have shown a significant prevalence of DED in pediatric populations, exacerbated by modern lifestyle changes such as increased screen time and environmental factors. Pediatric DED (PeDED) often goes underdiagnosed due to a lack of tailored diagnostic tools and the misattribution of symptoms to other conditions.

Methods

This Delphi study, conducted by a European panel of six ophthalmology experts sought to address expert consensus in pending challenges of PeDED.

Results

Over two rounds of surveys, 34 experts reached consensus on 39 of 46 statements, highlighting the need for age-specific diagnostic criteria and treatment protocols. The study identified environmental and lifestyle factors, such as screen time and ocular allergies, as significant risk factors for PeDED. There was strong consensus on the importance of adapting adult DED definitions and treatment approaches to better suit pediatric patients. The study also emphasized the cautious use of treatments like topical steroids or oral macrolides, especially in younger children.

Conclusion

The findings underscore the necessity for standardized clinical practices in diagnosing and managing PeDED, with a focus on improving the quality of life for affected children. Further research is required to validate these findings and develop comprehensive guidelines that cater to the unique needs of the pediatric population.

干眼病（DED）是一种有症状的多因素眼表疾病，主要特征是泪膜不稳定，可导致眼表损伤。虽然传统上与成人有关，但最近的研究表明，儿童人群中DED的患病率很高，并且由于现代生活方式的改变（如屏幕时间增加和环境因素）而加剧。由于缺乏量身定制的诊断工具以及将症状错误地归因于其他疾病，儿科DED经常被误诊。该德尔菲研究由6名欧洲眼科专家组成的小组进行，旨在解决PeDED面临的挑战中的专家共识。结果在两轮调查中，34位专家对46项声明中的39项达成共识，强调了针对年龄的诊断标准和治疗方案的必要性。该研究确定了环境和生活方式因素，如屏幕时间和眼部过敏，是ed的重要风险因素。对于调整成人DED的定义和治疗方法以更好地适应儿科患者的重要性，人们达成了强烈的共识。该研究还强调了局部类固醇或口服大环内酯类药物等治疗方法的谨慎使用，特别是在年幼的儿童中。结论本研究结果强调了在诊断和管理PeDED时标准化临床实践的必要性，重点是提高患儿的生活质量。需要进一步的研究来验证这些发现，并制定全面的指导方针，以满足儿科人群的独特需求。

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引用次数: 0

Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function Pard3 通过调节顶端-基底极性、细胞骨架组织和紧密连接介导的屏障功能，促进角膜上皮分层和平衡。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-04 DOI: 10.1016/j.jtos.2025.04.001

Mehak Vohra , Simran Kumar , Peri Sohnen , Satinder Kaur , Sudha Swamynathan , Tomonori Hirose , Zbynek Kozmik , Shivalingappa K. Swamynathan

Purpose

To document the expression of apical-basal polarity (ABP) determinants in the mouse corneal epithelium (CE) and elucidate the functions of Pard3 in establishment and maintenance of ABP, stratification, homeostasis, and barrier function in the CE.

Methods

Pard3^Δ/ΔC mice (Pard3^LoxP/LoxP; Aldh3A1-Cre/+) with cornea-specific Pard3 ablation were generated by breeding Aldh3A1-Cre/+ with Pard3^LoxP/LoxP mice. The control (Aldh3A1-Cre/+ or Pard3^LoxP/LoxP alone) and Pard3^Δ/ΔC corneal histology, ocular surface properties, barrier function, and actin cytoskeleton were assessed by Haematoxylin and Eosin staining of paraformaldehyde-fixed, paraffin-embedded tissues, scanning electron microscopy, fluorescein staining, and phalloidin staining, respectively. The expression of specific markers of interest was evaluated by qRT-PCR, immunoblots and immunofluorescent staining.

Results

Dynamic changes were observed in the expression and localization of ABP determinants as the CE stratified and matured between post-natal day 5 (PN5) and PN52. Adult Pard3^Δ/ΔC CE contained fewer cell layers with rounded basal cells, and loosely adherent superficial cells lacking microplicae. Adult Pard3^Δ/ΔC CE also displayed impaired barrier function with decreased expression of tight junction, adherens junction, and desmosome components, disrupted actin cytoskeletal organization, increased proliferation, and upregulation of transcription factors that drive epithelial-mesenchymal transition (EMT).

Conclusions

Disruption of ABP in Pard3^Δ/ΔC CE, altered expression of cell junction complex components and disorganized actin cytoskeleton, increased cell proliferation, and upregulated EMT transcription factors suggest that the ABP-determinant Pard3 promotes CE features while suppressing mesenchymal cell fate. Collectively, these results elucidate that Pard3-mediated ABP is essential for CE stratification, homeostasis and barrier function.

目的：研究小鼠角膜上皮（CE）中顶基极性（ABP）决定因子的表达，并阐明par3在角膜上皮中ABP的建立和维持、分层、稳态和屏障功能中的作用。方法：Pard3Δ/ΔC小鼠(Pard3LoxP/LoxP；Aldh3A1-Cre/+与Pard3LoxP/LoxP小鼠杂交产生具有角膜特异性par3消融的Aldh3A1-Cre/+。对照（Aldh3A1-Cre/+或Pard3LoxP/LoxP单独）和Pard3Δ/ΔC分别通过多聚甲醛固定组织、石蜡包埋组织的Haematoxylin和Eosin染色、扫描电镜、荧光素染色和phalloidin染色来评估角膜组织学、眼表特性、屏障功能和肌动蛋白细胞骨架。通过qRT-PCR、免疫印迹和免疫荧光染色评价感兴趣的特异性标志物的表达。结果：在出生后第5天（PN5）和第52天之间，随着CE的分层和成熟，ABP决定因子的表达和定位发生了动态变化。成人Pard3Δ/ΔC CE的细胞层较少，基底细胞为圆形，表面细胞贴壁松散，缺乏微皱褶。成人Pard3Δ/ΔC CE也表现出屏障功能受损，紧密连接、粘附连接和桥粒成分的表达减少，肌动蛋白细胞骨架组织被破坏，增殖增加，驱动上皮-间质转化（EMT）的转录因子上调。结论：Pard3Δ/ΔC CE中ABP的破坏，细胞连接复合物组分和无组织肌动蛋白细胞骨架的表达改变，细胞增殖增加，EMT转录因子上调，表明ABP决定因子par3促进CE特征，同时抑制间充质细胞的命运。总的来说，这些结果阐明了pard3介导的ABP对CE分层、体内平衡和屏障功能至关重要。

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引用次数: 0

Prevalence and antimicrobial susceptibility pattern of coagulase-negative Staphylococci isolated from ocular infections: A systematic review and meta-analysis 眼部感染中分离的凝固酶阴性葡萄球菌的患病率和抗菌药物敏感性模式：一项系统综述和荟萃分析。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-04 DOI: 10.1016/j.jtos.2025.03.006

Abolfazl Rafati Zomorodi , Maryam Mohammadi , Zahra Gholizadeh Farshi , Mohammad Hassan Parvizi Mashhadi , Sasan Pourbagher Benam , Mohammad Motamedifar

Bacteria are the leading cause of ocular infections (OIs), accounting for 32 %–74 % of cases globally. Coagulase-negative Staphylococci (CoNS) are frequently identified as the main causative pathogens of all types of OIs. This study systematically reviewed the prevalence of CoNS and their resistance rates to ciprofloxacin, chloramphenicol, tetracycline, and trimethoprim/sulfamethoxazole in OIs worldwide.

We conducted a comprehensive search of publications from January 1, 2000, to May 19, 2024, using three major databases: Scopus, Web of Science, and PubMed. Statistical analyses were performed with Stata 14.0, employing the Metaprop package to calculate pooled prevalence and confidence intervals. A random-effects model with double arcsine transformations stabilized variance in meta-analyses, and publication bias was evaluated using the “metabias” command. If bias was detected, we adjusted prevalence using the trim-and-fill method. A significant level of 0.05 was set for all analyses.

Out of 2116 articles, 214 were eligible for data extraction. The pooled prevalence of CoNS isolates in OIs was 25 % (95 % CI: 21–28; I² = 99.7 %), with Europe showing the highest prevalence at 30 % (95 % CI: 15–46; I²: 99.9 %) and Asia the lowest at 21 % (95 % CI: 19–24; I²: 98.68 %). The pooled prevalence of resistance among CoNS isolates from patients with OIs was 27 % (95 % CI: 19–35) for ciprofloxacin, 23 % (95 % CI: 12–34) for chloramphenicol, 41 % (95 % CI: 33–49) for tetracycline, and 40 % (95 % CI: 29–51) for trimethoprim/sulfamethoxazole.

In conclusion, CoNS are significant pathogens in OIs, highlighting the need for improved diagnostic tests and updated management guidelines globally.

细菌是眼部感染的主要原因，占全球病例的32%至74%。凝固酶阴性葡萄球菌（con）常被认为是所有类型oi的主要致病病原体。本研究系统回顾了全球oi中con的患病率及其对环丙沙星、氯霉素、四环素和甲氧苄啶/磺胺甲恶唑的耐药率。我们对2000年1月1日至2024年5月19日的出版物进行了全面的检索，使用了三个主要数据库：Scopus， Web of Science和PubMed。采用Stata 14.0进行统计分析，采用Metaprop软件包计算总患病率和置信区间。采用双反正弦变换的随机效应模型稳定了meta分析中的方差，并使用“meta”命令评估发表偏倚。如果检测到偏倚，我们使用修整填充法调整患病率。所有分析的显著水平为0.05。在2,116篇文章中，214篇符合数据提取条件。在oi中，con分离株的总患病率为25% (95% CI: 21-28；I2 = 99.7%)，欧洲的患病率最高，为30% (95% CI: 15-46；I2: 99.9%)，亚洲最低，为21% (95% CI: 19-24；I2: 98.68%)。来自OIs患者的con分离株的总耐药率为环丙沙星27% (95% CI: 19-35)，氯霉素23% (95% CI: 12-34)，四环素41% (95% CI: 33-49)，甲氧苄啶/磺胺甲恶唑40% （95% CI: 29-51）。总之，con是oi的重要病原体，这突出了全球改进诊断检测和更新管理指南的必要性。

{"title":"Prevalence and antimicrobial susceptibility pattern of coagulase-negative Staphylococci isolated from ocular infections: A systematic review and meta-analysis","authors":"Abolfazl Rafati Zomorodi , Maryam Mohammadi , Zahra Gholizadeh Farshi , Mohammad Hassan Parvizi Mashhadi , Sasan Pourbagher Benam , Mohammad Motamedifar","doi":"10.1016/j.jtos.2025.03.006","DOIUrl":"10.1016/j.jtos.2025.03.006","url":null,"abstract":"<div><div>Bacteria are the leading cause of ocular infections (OIs), accounting for 32 %–74 % of cases globally. Coagulase-negative <em>Staphylococci</em> (CoNS) are frequently identified as the main causative pathogens of all types of OIs. This study systematically reviewed the prevalence of CoNS and their resistance rates to ciprofloxacin, chloramphenicol, tetracycline, and trimethoprim/sulfamethoxazole in OIs worldwide.</div><div>We conducted a comprehensive search of publications from January 1, 2000, to May 19, 2024, using three major databases: Scopus, Web of Science, and PubMed. Statistical analyses were performed with Stata 14.0, employing the Metaprop package to calculate pooled prevalence and confidence intervals. A random-effects model with double arcsine transformations stabilized variance in meta-analyses, and publication bias was evaluated using the “metabias” command. If bias was detected, we adjusted prevalence using the trim-and-fill method. A significant level of 0.05 was set for all analyses.</div><div>Out of 2116 articles, 214 were eligible for data extraction. The pooled prevalence of CoNS isolates in OIs was 25 % (95 % CI: 21–28; I<sup>2</sup> = 99.7 %), with Europe showing the highest prevalence at 30 % (95 % CI: 15–46; I<sup>2</sup>: 99.9 %) and Asia the lowest at 21 % (95 % CI: 19–24; I<sup>2</sup>: 98.68 %). The pooled prevalence of resistance among CoNS isolates from patients with OIs was 27 % (95 % CI: 19–35) for ciprofloxacin, 23 % (95 % CI: 12–34) for chloramphenicol, 41 % (95 % CI: 33–49) for tetracycline, and 40 % (95 % CI: 29–51) for trimethoprim/sulfamethoxazole.</div><div>In conclusion, CoNS are significant pathogens in OIs, highlighting the need for improved diagnostic tests and updated management guidelines globally.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 227-235"},"PeriodicalIF":5.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A tribute to Gary N. Foulks, M.D. (1944–2025) and his contributions to the ocular surface 致敬Gary N. Foulks， M.D.（1944-2025）和他对《眼表》的贡献。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-02 DOI: 10.1016/j.jtos.2025.03.009

Michael H. Goldstein , Deepinder Dhaliwal , Ed Isbey , Stephen Pflugfelder , Mark J. Mannis , Gary D. Novack

引用次数: 0

Smad4 deficiency ameliorates the progressive corneal stroma thinning caused by the loss of Tbr1 Smad4缺乏可改善由Tbr1缺失引起的进行性角膜基质变薄。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-01 Epub Date: 2025-01-31 DOI: 10.1016/j.jtos.2025.01.013

Yong Yuan , Shingo Yasuda , Kaitlyn L. Funk , Winston Kao , Shizuya Saika , Adam Kaufman , Chia-Yang Liu

Purpose

To understand how Tbr1 and Smad4 play a pivotal role in controlling ECM synthesis versus degradation for maintaining corneal stromal homeostasis and otherwise leading to corneal ectasia.

Methods

Keratocyte-specific and inducible knockout (iKO) of Tbr1, Smad4, or Tbr1/Smad4 double KO (iDKO) mice were generated. OCT was used to assess corneal thickness in vivo. Masson's trichrome and collagen hybridizing peptide stainings were performed to examine collagen expression. Immunostaining with an anti-cathepsin B antibody was used to assess ECM degradation. Cathepsin B inhibitor, CA-074Me, eyedrop was conducted to test its effect on treating stromal thinning in Tbr1 iKO mice.

Results

Tbr1 iKO and Smad4 iKO displayed corneal thinning, but Tbr1 iKO revealed a progressive and more severe pathology than Smad4 iKO. Tbr1 iKO cornea lost most of its stroma and thus a dome shape. Collagen ECM is evenly distributed in Smad4 iKO as well as control littermates but was lost mainly in the anterior stroma of the Tbr1 iKO. Interestingly, Tbr1/Smad4 iDKO ameliorated Tbr1 iKO phenotype. The basal level of Cathepsin b (Ctsb) could be detected in the control stroma but was significantly increased in the Tbr1 iKO stromal cells and this effect was canceled in Tbr1/Smad4 iDKO. CA-074Me eyedrops administration significantly inhibited progressive corneal thinning caused by the Tbr1 iKO.

Conclusion

Our data from Tbr1/Smad4 iDKO argued that Smad4 played a pivotal role in controlling Tbr1-dependent ECM synthesis and Tbr1-independent ECM degradation to maintain corneal stromal integrity and homeostasis.

目的：了解Tbr1和Smad4如何在控制ECM合成和降解中发挥关键作用，从而维持角膜基质稳态，从而导致角膜扩张。方法：制备角化细胞特异性诱导敲除（iKO） Tbr1、Smad4或Tbr1/Smad4双KO （iDKO）小鼠。OCT在体内评估角膜厚度。马松三色染色和胶原杂交肽染色检测胶原蛋白表达。用抗组织蛋白酶B抗体免疫染色来评估ECM的降解。采用组织蛋白酶B抑制剂CA-074Me滴眼液，观察其对tbr1iko小鼠间质变薄的治疗作用。结果：Tbr1 iKO和Smad4 iKO表现为角膜变薄，但Tbr1 iKO比Smad4 iKO表现为进行性且更严重的病理。tbr1ko角膜失去了大部分基质，因此呈圆顶状。胶原蛋白ECM在Smad4和对照幼崽中均匀分布，但主要在Tbr1幼崽的前间质中丢失。有趣的是，Tbr1/Smad4 iDKO改善了Tbr1 iKO表型。在对照基质中可以检测到组织蛋白酶b （Ctsb）的基础水平，但在Tbr1 iKO基质细胞中显著升高，而在Tbr1/Smad4 iDKO中这种影响被消除。CA-074Me滴眼液可显著抑制由Tbr1 iKO引起的进行性角膜变薄。结论：我们来自Tbr1/Smad4 iDKO的数据表明，Smad4在控制Tbr1依赖性ECM合成和Tbr1非依赖性ECM降解中发挥关键作用，以维持角膜基质的完整性和稳态。

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引用次数: 0

Corneal epithelial cells upregulate macropinocytosis to engulf metabolically active axonal mitochondria released by injured axons 角膜上皮细胞上调巨噬细胞吞噬受损轴突释放的代谢活跃的轴突线粒体

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-01 DOI: 10.1016/j.jtos.2025.03.007

Sonali Pal-Ghosh , Himani Datta-Majumdar , Soneha Datta , Shelly Dimri , Jordan Hally , Hugo Wehmeyer , Zhong Chen , Mitchell Watsky , Jian-Xing Ma , Wentao Liang , Mary Ann Stepp

Purpose

To determine the mechanisms used to internalize mitochondria by corneal epithelial cells after in vivo corneal trephine injury and in vitro in corneal epithelial cells.

Methods

Male and female mice were subjected to trephine injury and euthanized immediately, 6, and 24 h after injury. Macropinocytosis was quantified in vivo using 70 kD fluorescent dextran. Mitochondrial content was assessed by immunofluorescence and metabolic activity quantified by Seahorse assay immediately and 6 h after injury. In vitro experiments using human corneal and limbal epithelial (HCLE) cells and isolated mitochondria were performed to assess mitochondrial transfer in the presence of the gap junction inhibitor 18α-glycyrrhetinc acid and the macropincytosis inhibitor ethylisopropylamiloride.

Results

Mitochondria accumulate within apical epithelial cell layers within minutes of trephine injury. Macropinocytosis also increases within minutes of trephine injury. Oxygen Consumption Rates increase in the corneal epithelium 6 h after trephine injury in males and females. Inhibiting gap junctions increases mitochondrial engulfment while inhibiting macropinocytosis prevents engulfment of mitochondria by corneal epithelial cells in vitro.

Conclusions

Molecules released by injured cells and severed axons induce macropinocytosis in corneal epithelial cells within minutes of trephine injury. An increase in oxygen consumption rate in the corneal epithelium after trephine injury indicates that axonal mitochondria can evade lysosomal degradation for at least 6 h. In vitro studies using isolated labeled and unlabeled mitochondria and control and mechanically stressed human corneal epithelial cells confirm the involvement of macropinocytosis in the engulfment of free and vesicle bound mitochondria by corneal epithelial cells.

目的探讨活体角膜环钻损伤和体外角膜上皮细胞内化线粒体的机制。方法将雄性和雌性小鼠分别于伤后即刻、6和24 h实施安乐死。用70kd荧光葡聚糖定量体内巨量红细胞增多。损伤后立即及6 h，用免疫荧光法测定线粒体含量，用海马法测定代谢活性。利用人角膜和角膜缘上皮（HCLE）细胞和分离的线粒体进行体外实验，以评估间隙连接抑制剂18α-甘草次酸和巨噬细胞症抑制剂乙基异丙基酰胺存在下的线粒体转移。结果环钻损伤后几分钟内，线粒体在顶端上皮细胞层内积累。环钻损伤后几分钟内巨噬细胞增多。环钻损伤后6小时，男性和女性角膜上皮耗氧量增加。抑制间隙连接增加线粒体吞噬，而抑制巨噬细胞作用可防止角膜上皮细胞对线粒体的吞噬。结论角膜环钻损伤后数分钟内，损伤细胞和断轴突释放的分子可诱导角膜上皮细胞巨噬细胞增多。角膜外伤后角膜上皮耗氧量的增加表明轴突线粒体可以逃避溶酶体降解至少6小时。使用分离的标记和未标记线粒体以及对照和机械应激的人角膜上皮细胞进行的体外研究证实，大胞饮作用参与角膜上皮细胞吞噬游离和囊泡结合的线粒体。

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引用次数: 0

Differential homing of monocytes and neutrophils in the epithelial layer of HSV-1 infected cornea regulates viral dissemination and wound healing 单核细胞和中性粒细胞在HSV-1感染角膜上皮层的差异归巢调节病毒传播和伤口愈合。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-01 Epub Date: 2025-01-08 DOI: 10.1016/j.jtos.2025.01.002

Mizumi Setia, Pratima Krishna Suvas, Mashidur Rana, Anish Chakraborty, Susmit Suvas

Purpose

To ascertain the homing of monocytes and neutrophils in the epithelium versus stroma of HSV-1 infected corneas at different stages of infection and functional significance of their anatomical location in virus-infected corneas.

Methods

The corneas of C57BL/6J mice were infected with HSV-1 McKrae. Mice were euthanized on different days post-infection. The epithelium and stroma were separated from the infected corneas, and flow cytometry was performed to characterize the myeloid cell subsets in the epithelium versus the stromal layers of an infected cornea. MACS columns were used to purify neutrophils or deplete myeloid cells from infected corneas. Corneal epithelial scratch assay was performed to ascertain the impact of neutrophils on epithelium wound healing.

Results

Our results showed a biphasic influx of monocytes in the epithelial but not the stromal layer of HSV-1-infected corneas. Furthermore, we noted the predominance of monocytes over neutrophils in the epithelium and the stromal layer of the cornea during the pre-clinical stage of corneal HSV-1 infection. However, neutrophils were the major myeloid cell subset in the epithelium and stroma during the clinical disease period of infection. Removal of monocytes from the infected epithelial layer during the pre-clinical stage promotes the dissemination of the virus. Interestingly, neutrophils localized in the corneal epithelium inhibit corneal epithelial wound healing.

Conclusions

Together, our data suggest that differential kinetics of monocytes and neutrophils homing in the epithelial layer regulate viral dissemination and epithelial wound healing in HSV-1-infected corneas.

目的：探讨1型单纯疱疹病毒感染角膜不同感染阶段单核细胞和中性粒细胞在上皮和间质中的归巢情况及其在病毒感染角膜中解剖位置的功能意义。方法：C57BL/6J小鼠角膜感染HSV-1 McKrae。小鼠在感染后的不同天数被安乐死。从感染的角膜中分离上皮和间质，用流式细胞术表征感染角膜上皮和间质层中的髓样细胞亚群。用MACS柱从感染的角膜中纯化中性粒细胞或清除髓样细胞。采用角膜上皮划伤实验确定中性粒细胞对角膜上皮创面愈合的影响。结果：我们的结果显示单核细胞双期内流于hsv -1感染的角膜上皮层而非间质层。此外，我们注意到在角膜HSV-1感染的临床前阶段，单核细胞在角膜上皮和间质层中的优势大于中性粒细胞。然而，在感染的临床疾病期间，中性粒细胞是上皮和间质中主要的骨髓细胞亚群。在临床前阶段从受感染的上皮层去除单核细胞会促进病毒的传播。有趣的是，角膜上皮内的中性粒细胞抑制角膜上皮伤口愈合。结论：总之，我们的数据表明，单核细胞和中性粒细胞在上皮层归巢的差异动力学调节了hsv -1感染角膜的病毒传播和上皮伤口愈合。

{"title":"Differential homing of monocytes and neutrophils in the epithelial layer of HSV-1 infected cornea regulates viral dissemination and wound healing","authors":"Mizumi Setia, Pratima Krishna Suvas, Mashidur Rana, Anish Chakraborty, Susmit Suvas","doi":"10.1016/j.jtos.2025.01.002","DOIUrl":"10.1016/j.jtos.2025.01.002","url":null,"abstract":"<div><h3>Purpose</h3><div>To ascertain the homing of monocytes and neutrophils in the epithelium versus stroma of HSV-1 infected corneas at different stages of infection and functional significance of their anatomical location in virus-infected corneas.</div></div><div><h3>Methods</h3><div>The corneas of C57BL/6J mice were infected with HSV-1 McKrae. Mice were euthanized on different days post-infection. The epithelium and stroma were separated from the infected corneas, and flow cytometry was performed to characterize the myeloid cell subsets in the epithelium versus the stromal layers of an infected cornea. MACS columns were used to purify neutrophils or deplete myeloid cells from infected corneas. Corneal epithelial scratch assay was performed to ascertain the impact of neutrophils on epithelium wound healing.</div></div><div><h3>Results</h3><div>Our results showed a biphasic influx of monocytes in the epithelial but not the stromal layer of HSV-1-infected corneas. Furthermore, we noted the predominance of monocytes over neutrophils in the epithelium and the stromal layer of the cornea during the pre-clinical stage of corneal HSV-1 infection. However, neutrophils were the major myeloid cell subset in the epithelium and stroma during the clinical disease period of infection. Removal of monocytes from the infected epithelial layer during the pre-clinical stage promotes the dissemination of the virus. Interestingly, neutrophils localized in the corneal epithelium inhibit corneal epithelial wound healing.</div></div><div><h3>Conclusions</h3><div>Together, our data suggest that differential kinetics of monocytes and neutrophils homing in the epithelial layer regulate viral dissemination and epithelial wound healing in HSV-1-infected corneas.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 69-82"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of a biweekly novel selenium sulfide-containing topical treatment in symptomatic contact lens wearers: An exploratory study 两周一次新型含硫化硒局部治疗对有症状的隐形眼镜佩戴者的影响：一项探索性研究。

IF 5.9 1区医学 Q1 OPHTHALMOLOGY

Ocular Surface

Pub Date : 2025-04-01 Epub Date: 2025-01-31 DOI: 10.1016/j.jtos.2025.01.015

Fiona Stapleton , Tianni Jia , Venita DePuy , Charles Bosworth , Marc Gleeson , Jacqueline Tan

Purpose

To explore effects of topical 1 % selenium sulfide on signs and symptoms in symptomatic contact lens-wearers, in an exploratory 4-month prospective placebo-controlled double-masked randomised trial.

Methods

Symptomatic wearers (Contact Lens Dry Eye Questionnaire-8 [CLDEQ-8] score>12) with meibomian gland dysfunction (meibomian gland score (MGS)≤12), were enrolled and received either active (AZR-MD-001-containing 1 % selenium sulfide), or vehicle ointment, to the lower eyelid margin twice-weekly. MGS, meibomian glands-yielding liquid secretion (MGYLS), lipid layer thickness, tear meniscus height, tear break-up time, tear evaporation rate, lid wiper epitheliopathy, CLDEQ-8 and comfortable wear time (CWT) were measured at baseline and to 4-months. Differences between active and placebo were compared to baseline.

Results

Fourteen participants (5M:9 F, 30.8 ± 13.8 years) completed the study. In the active group, change in MGS from baseline improved by 1-month (mean difference 7.9 ± 8.0, p = 0.03), to 4-months (16.0 ± 11.3, p < 0.01). MGYLS improved from baseline by 1.5-months (4.0 ± 3.3) to 4-months (4.1 ± 4.3, p < 0.01). In the vehicle, change in MGS (12.1 ± 10.7) and MGYLS (3.9 ± 3.2) were improved at 4-months only (p < 0.01). CLDEQ-8 score improved at 1-month and 4-months compared to baseline (−4.4 ± 3.2, −5.1 ± 4.7, p ≤ 0.02) in the active and at 4-months only in the vehicle group (−4.4 ± 6.4, p = 0.02). In the active group, CLDEQ-8 visual function scores improved at 1- and 4-months (p ≤ 0.02) and CWT at 4-months (median 7 vs.10 h, p = 0.025). Other signs were unchanged.

Conclusions

This exploratory study indicates that twice-weekly use of AZR-MD-001 ointment can rapidly improve gland patency and secretion in symptomatic contact lens-wearers. AZR-MD-001 reduced changeable/blurry vision and prolonged CWT, suggesting relevant future endpoints.

目的：在一项为期4个月的前瞻性安慰剂对照双盲随机试验中，探讨局部1%硫化硒对有症状隐形眼镜佩戴者体征和症状的影响。方法：纳入睑板腺功能障碍（睑板腺评分(MGS)≤12）的有症状配戴者（隐形眼镜干眼问卷-8 [CLDEQ-8]评分bbbb12），每周两次接受活性（含1%硫化硒的azr - md -001）或载体软膏下睑缘。在基线和4个月时测量MGS、睑板产腺液分泌（MGYLS）、脂质层厚度、泪液半月板高度、泪液破裂时间、泪液蒸发率、擦皮上皮病变、CLDEQ-8和舒适磨损时间（CWT）。与基线比较活性和安慰剂之间的差异。结果：14名参与者（年龄：9岁，30.8±13.8岁）完成了研究。在活性组中，MGS的变化从基线改善了1个月（平均差值7.9±8.0,p=0.03）到4个月（16.0±11.3）。结论：本探索性研究表明，每周两次使用AZR-MD-001软膏可以快速改善有症状的隐形眼镜佩戴者的腺体通畅和分泌。AZR-MD-001减少可变/模糊视力和延长CWT，提示相关的未来终点。

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