Ocular Surface最新文献

{"title":"Application of stem cell-derived exosomes in anterior segment eye diseases: A comprehensive update review","authors":"Masoud Khorrami-Nejad ,&nbsp;Hesam Hashemian ,&nbsp;Ali Majdi ,&nbsp;Khosrow Jadidi ,&nbsp;Hossein Aghamollaei ,&nbsp;Ali Hadi","doi":"10.1016/j.jtos.2025.01.012","DOIUrl":"10.1016/j.jtos.2025.01.012","url":null,"abstract":"<div><div>Mesenchymal stem cell (MSC) therapy has emerged as a promising approach for addressing various eye-related conditions. Yet, its clinical application faces challenges due to issues such as limited biocompatibility and difficulties in effectively delivering treatment to specific ocular tissues. Recent studies have shifted attention towards MSC-derived exosomes, which share similar regenerative, reparative, and immunomodulatory capabilities with their origin cells. This review delves into the latest research on the use of MSC-derived exosomes for treating anterior segment diseases of the eye. It explores the exosomes' composition, biological functions, and the methods used for their isolation, as well as their roles in disease progression, diagnosis, and therapy. The review critically assesses the therapeutic advantages and mechanisms of action of MSC-derived exosomes in treating conditions like dry eye disease, Sjogren's syndrome, keratoconus, corneal lesions, and corneal allograft rejection. Additionally, it discusses the obstacles and future prospects of employing MSC-derived exosomes as innovative therapies for anterior segment eye diseases. This comprehensive overview underscores the significant potential of MSC-derived exosomes in transforming the treatment paradigm for anterior segment eye disorders, while also highlighting the necessity for further research to enhance their clinical application.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 209-219"},"PeriodicalIF":5.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070467","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}

{"title":"Label-free quantitative imaging of conjunctival goblet cells","authors":"Noseong Park ,&nbsp;Suil Jeon ,&nbsp;Seonghan Kim ,&nbsp;Jungbin Lee ,&nbsp;Jin Suk Ryu ,&nbsp;Wan Jae Choi ,&nbsp;Chang Ho Yoon ,&nbsp;Chulmin Joo ,&nbsp;Ki Hean Kim","doi":"10.1016/j.jtos.2025.01.009","DOIUrl":"10.1016/j.jtos.2025.01.009","url":null,"abstract":"<div><h3>Purpose</h3><div>To introduce and validate quantitative oblique back-illumination microscopy (qOBM) as a label-free, high-contrast imaging technique for visualizing conjunctival goblet cells (GCs) and assessing their functional changes.</div></div><div><h3>Methods</h3><div>qOBM was developed in conjunction with moxifloxacin-based fluorescence microscopy (MBFM), which was used for validating GC imaging. Initial validation was conducted with polystyrene beads, followed by testing on normal mouse conjunctiva under both <em>ex-vivo</em> and <em>in-vivo</em> conditions. Longitudinal qOBM imaging was performed on <em>ex-vivo</em> mouse conjunctiva exposed to hyperosmotic stress (induced by 1000 mOsm/kg NaCl solution) and normal saline (300 mOsm/kg balanced salt solution, BSS). Imaging was conducted at baseline and at 15- and 30-min instillation. Results were compared to those of MBFM and periodic acid-Schiff (PAS) staining. A similar longitudinal study was performed <em>in-vivo</em>, and the outcomes were analyzed.</div></div><div><h3>Results</h3><div>qOBM accurately imaged polystyrene beads, with measured phase delays matching theoretical predictions. In normal mouse conjunctiva, qOBM visualized GCs in high contrast, confirmed by MBFM, and the average phase delay was 0.59 ± 0.25 radians. Under hyperosmotic stress, qOBM detected a significant reduction in GC phase delays, decreasing to levels of the surrounding tissue (−0.07 ± 0.14 radians). In normal conditions, no notable changes were observed in GCs. <em>In</em>-<em>vivo</em> imaging results were consistent with <em>ex-vivo</em> findings. Statistical analysis further characterized these changes. The results were consistent with MBFM and PAS staining.</div></div><div><h3>Conclusions</h3><div>qOBM is a high-contrast, label-free imaging modality that enables the functional assessment of GCs. This technique holds significant potential for advancing research and clinical diagnostics related to ocular surface diseases.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 156-163"},"PeriodicalIF":5.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043998","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}

{"title":"Relative importance of tear homeostatic signs for the diagnosis of dry eye disease","authors":"James S. Wolffsohn ,&nbsp;Sònia Travé-Huarte ,&nbsp;Fiona Stapleton ,&nbsp;Laura E. Downie ,&nbsp;Marc-Matthias Schulze ,&nbsp;Sarah Guthrie ,&nbsp;Ulrike Stahl ,&nbsp;Michael T.M. Wang ,&nbsp;Jennifer P. Craig","doi":"10.1016/j.jtos.2025.01.010","DOIUrl":"10.1016/j.jtos.2025.01.010","url":null,"abstract":"<div><h3>Aim</h3><div>Disease misdiagnosis is more likely if standardised diagnostic criteria are not used. This study systematically examined the effect on diagnosing dry eye disease (DED), when tests for evaluating tear film homeostasis were included or excluded from a multi-test protocol.</div></div><div><h3>Method</h3><div>For 1,427 participants across five sites, data for the full suite of diagnostic tests defined in the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) Diagnostic Methodology report algorithm were evaluated; diagnostic sensitivity was calculated when individual signs were removed, and when different combinations of signs were required.</div></div><div><h3>Results</h3><div>Evaluating just one of the three TFOS DEWS II homeostatic signs resulted in between 12.3 % and 36.2 % of patients who met the DED diagnostic criteria not being assigned this diagnosis. While comprehensive ocular surface staining evaluation, comprising of corneal, conjunctival and lid margin staining, in combination with symptoms had the highest sensitivity (87.7 %) of the three markers, the sensitivity dropped to 44.6 % if only corneal staining was evaluated. Omitting either non-invasive tear breakup time or tear osmolarity each dropped the sensitivity by &lt;5 %. The prevalence of DED was substantially reduced if a diagnosis required symptoms and two of the three signs to be present (by 43.7 %–61.2 %) and by 65.9 % if all three signs indicating a loss of tear film homeostasis were required. The outcomes of the analysis did not change significantly across differing severities of DED symptoms.</div></div><div><h3>Conclusions</h3><div>The TFOS DEWS II diagnostic algorithm of symptoms plus assessing for a tear film (non-invasive tear breakup time or tear osmolarity) and ocular surface sign can be considered a robust and appropriate approach for DED diagnosis.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 151-155"},"PeriodicalIF":5.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics and single-cell RNA-sequencing revealed dendritic cell-mediated inflammation in keratoconus","authors":"Shiqi Luo ,&nbsp;Jingying Li ,&nbsp;Yan Yang ,&nbsp;Yang Jiang ,&nbsp;Ying Jie ,&nbsp;Wei Ge","doi":"10.1016/j.jtos.2025.01.008","DOIUrl":"10.1016/j.jtos.2025.01.008","url":null,"abstract":"<div><div>Keratoconus (KC) is a corneal disorder characterized by central corneal protrusion and thinning. In this study, spatial transcriptomics was employed to investigate molecular and cellular variations in KC, revealing a distinct pattern of inflammatory responses across the cornea. Upregulation of inflammatory processes was observed in the central cornea, while downregulation was noted in the periphery, indicating complex regional inflammatory changes in the KC cornea. Integration with single-cell RNA sequencing (scRNA-seq) further identified enhanced interactions between dendritic cells (DCs) and stromal cells, particularly mediated via the IL-1β pathway, alongside increased matrix metalloproteinase (MMP) production by corneal stromal cells, underscoring the role of inflammation in KC pathogenesis. <em>In vitro</em> and <em>in vivo</em> experiments confirmed that activated DCs promoted the matrix degradation activity of stromal cells, thereby exacerbating KC pathology. Notably, inhibition of the IL-1β pathway effectively mitigated the progression of KC. These findings provide a comprehensive spatial, cellular, and molecular characterization of KC, demonstrating its inflammatory nature. The results also highlight the importance of inflammation in the peripheral cornea for early diagnosis and suggest that anti-inflammatory treatments could serve as potential adjuvant therapy for KC.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 134-150"},"PeriodicalIF":5.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018578","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}

{"title":"Hyperosmotic stress-induced NLRP3 inflammasome activation via the mechanosensitive PIEZO1 channel in dry eye corneal epithelium","authors":"Lili Lian ,&nbsp;Xuanqiao Ye ,&nbsp;Zimo Wang ,&nbsp;Jiuxiao Li ,&nbsp;Jiahe Wang ,&nbsp;Letong Chen ,&nbsp;Peter S. Reinach ,&nbsp;Xiaoyin Ma ,&nbsp;Wei Chen ,&nbsp;Qinxiang Zheng","doi":"10.1016/j.jtos.2025.01.005","DOIUrl":"10.1016/j.jtos.2025.01.005","url":null,"abstract":"<div><div>The activation of the NLRP3 inflammasome by hyperosmotic stress is a critical pathophysiological response in dry eye disease (DED), driving the chronic cycle of inflammation on the ocular surface. The specific mechanism underlying hyperosmotic mechanical stimulation activates the NLRP3 inflammasome remains unclear. This study provides evidence that PIEZO1, a mechanosensitive ion channel, functions as the primary receptor for corneal epithelial cells in sensing mechanical stimulation induced by tear hyperosmolarity. Inhibition of PIEZO1 significantly reduces NLRP3 inflammasome-associated pyroptosis in corneal epithelial cells. These findings suggest a therapeutic strategy targeting mechanosensitive ion channels to manage chronic ocular surface inflammation in DED patients.</div><div>Structured Abstract.</div></div><div><h3>Purpose</h3><div>PIEZO1 modulates the inflammatory response by translating mechanical signals from osmotic pressure into biological processes. This study investigates the functional role of PIEZO1 in activating the NLRP3 inflammasome in corneal epithelial cells under hyperosmotic stress and evaluates its contribution to the pathogenesis of dry eye disease (DED).</div></div><div><h3>Methods</h3><div>In the in vitro experiments, immortalized human corneal epithelial cells (HCECs) were cultured under hyperosmotic conditions (450mOsm). For in vivo studies, a dry eye disease mouse model was established by subcutaneous injection of scopolamine (SCOP) in C57BL/6 mice. After successfully inducing the dry eye model, corneal epithelial cell damage was assessed through corneal fluorescein staining scores and TUNEL assays. Protein expression levels were examined via western blotting and immunofluorescence staining, while mRNA expression was analyzed using quantitative RT-PCR. Activation of the NLRP3 inflammasome was evaluated by measuring IL-1β protein cleavage and the formation of ASC speckles.</div></div><div><h3>Results</h3><div>In the DED model, activation of the NLRP3 inflammasome was detected in corneal epithelial cells, along with increased expression of PIEZO1. The PIEZO1-specific agonist Yoda1 induced upregulation of NLRP3 inflammasome-related gene expression and triggered NLRP3 inflammasome activation. Conversely, silencing PIEZO1 using siRNA or inhibiting its activity suppressed hyperosmotic stress-induced changes in NLRP3 inflammasome-related gene expression and activation. In vivo, PIEZO1 inhibition effectively prevented NLRP3 inflammasome activation in corneal epithelial cells and restored the damaged phenotype associated with dry eye disease.</div></div><div><h3>Conclusion</h3><div>Hyperosmotic stress-induced activation of the NLRP3 inflammasome in corneal epithelial cells is mediated through PIEZO1 activation. The identification of PIEZO1's role in this DED-related pathophysiological response highlights its potential as a therapeutic target for mitigating inflammation in clinical settings.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 106-118"},"PeriodicalIF":5.9,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019455","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}

{"title":"Prevalence of dry eye disease in Spain: A population-based survey (PrevEOS)","authors":"José M. Benítez-del-Castillo ,&nbsp;Bárbara Burgos-Blasco","doi":"10.1016/j.jtos.2025.01.006","DOIUrl":"10.1016/j.jtos.2025.01.006","url":null,"abstract":"<div><h3>Purpose</h3><div>To determine the countrywide prevalence of dry eye disease (DED) at the population level in Spain, and associated risks.</div></div><div><h3>Methods</h3><div>This was a cross-sectional study based on a telephone survey conducted in 2022. Participants from the general population were selected by sex, age, region, and population of residence to ensure the representativeness of the Spanish population. Participants responded to 42 questions on sociodemographic characteristics, clinical diagnosis of DED, DED-related symptoms, comorbidities, prior eye surgery, current intake of specific drugs, use of contact lenses or artificial tears, and the use of digital screens. The criteria from the Women's Health Study (WHS) and the Beijing Eye Study (BES) were used to determine DED.</div></div><div><h3>Results</h3><div>A total of 3019 interviews were conducted. The prevalence of DED according to WHS criteria was 16.6 % (10.9 % men versus 21.3 % women, p &lt; 0.001); 12.3 % of respondents reported having a clinical diagnosis of DED. The age group 18–29 years presented a high frequency of symptoms. According to the BES criteria, the prevalence of DED was 22.5 % (20.2 % of men, 24.6 % of women, p = 0.005). Diabetes, glaucoma, and blepharitis, the intake of antidepressants/anxiolytics, blood pressure drugs, and sleeping pills, and prior eye surgery were significant risk factors (p &lt; 0.0001). The use of digital screens for &lt;6 h per day was significantly associated with DED.</div></div><div><h3>Conclusions</h3><div>Prevalence of DED in Spain was high among young adults, who presented a combination of high frequency of symptoms and low rates of clinical diagnosis. Increased awareness should be promoted in this population group.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 126-133"},"PeriodicalIF":5.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective self-controlled study on the alterations of the ocular surface and conjunctival transcriptomic profile associated with prolonged exposure to video display terminals","authors":"Ling Li ,&nbsp;Xinhao Zhu ,&nbsp;Weihao Xu ,&nbsp;Mali Dai ,&nbsp;Zihao Liu ,&nbsp;Yanxiao Li ,&nbsp;Yiting Fang ,&nbsp;Jinyang Li ,&nbsp;Wei Chen","doi":"10.1016/j.jtos.2025.01.007","DOIUrl":"10.1016/j.jtos.2025.01.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the impact of prolonged and intense exposure to video display terminals (VDTs) on ocular surface homeostasis.</div></div><div><h3>Methods</h3><div>30 subjects limited daily VDT usage to less than 3 h for one week, then extended usage to more than 8 h/day for the next three weeks. Ocular symptoms and signs were evaluated weekly using the Ocular Surface Disease Index (OSDI) questionnaire and clinical examinations. Eyelid margins and meibomian glands were examined, and ocular surface samples were collected for transcriptomic analysis.</div></div><div><h3>Results</h3><div>Average daily VDT time increased from 2.55 ± 0.46 h initially to 11.17 ± 2.45, 11.75 ± 2.63, and 10.89 ± 2.41 h over three weeks. The dry eye diagnosis rate rose from 6.67 % to 51.67 %. Total OSDI score (P = 0.008), symptoms score (P = 0.014), and visual function score (P = 0.002) significantly increased. Mean fluorescein break-up time (FBUT) decreased from 6.46s to 3.08s. Corneal fluorescein staining (CFS) score (P &lt; 0.001) and lissamine green conjunctival staining (LCjs) score (P = 0.036) worsened. Ocular redness index (RI) increased at 1 week and 3 weeks (P = 0.007, P = 0.001). Telangiectasia scores of both upper and lower eyelid margins increased at 3 weeks (P = 0.002, P &lt; 0.001). Meibomian gland orifice blockage worsened (P = 0.014, P = 0.002). Transcriptomic analysis revealed dynamic alterations in ocular surface gene expression, including inflammatory and hormonal responses. MUC5AC and TFF1 genes showed negative correlations with OSDI and conjunctival staining score, respectively.</div></div><div><h3>Conclusion</h3><div>Prolonged VDT exposure deteriorates ocular surface symptoms and signs, with significant inflammatory responses and hormonal activity indicating an imbalance in ocular surface homeostasis.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 94-105"},"PeriodicalIF":5.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019452","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}

{"title":"A novel Schirmer strip-based tear matrix metalloproteinase measurement in dry eye evaluation","authors":"Di Chen ,&nbsp;Wubi Li ,&nbsp;Shan Yang ,&nbsp;Hang Song ,&nbsp;Yu Di ,&nbsp;Weixing Zhong ,&nbsp;Miao Zhang ,&nbsp;Qin Long ,&nbsp;Ying Li ,&nbsp;Chan Zhao","doi":"10.1016/j.jtos.2025.01.004","DOIUrl":"10.1016/j.jtos.2025.01.004","url":null,"abstract":"<div><h3>Purpose</h3><div>The diagnosis and evaluation of dry eye require easy-to-use, precise, and consistent tools in clinical setting. Matrix metalloproteinase 9 (MMP-9) has been proven to be a reliable indicator of dry eye inflammation. The aim of this study is to establish an Eu-time resolved fluorescence immunochromatography (Eu-TRFICO) method for quantitative detection of MMP-9 in human tear based upon widely used Schirmer strips.</div></div><div><h3>Methods</h3><div>The Eu-TRFICO method for Schirmer strip-based tear MMP-9 measurements were optimized and assembled. The sensitivity, repeatability and homogeneity were evaluated using MMP-9 standard dilutions. The diagnostic and treatment monitoring performance were evaluated in both dry eye patients and normal subjects.</div></div><div><h3>Results</h3><div>The standard curve equation was y = 0.0037 + 8.0692/[1+ (x/188.322)^−0.8972] (R2 = 0.99998), and the sensitivity was 0.25 ng/mL. The Schirmer strip-based MMP-9 measurements showed acceptable repeatability and homogeneity with different saturation length in both low and high standard solutions. A total of 162 participants (162 eyes) were enrolled in this study, including 41 normal and 121 dry eye subjects. This method exhibited a sensitivity of 74.17 % and specificity of 77.5 % for dry eye diagnosis, with an AUC value of 0.8275, and cutoff value of 150.67 ng/mL, using normal subjects as negative control. The tear MMP-9 concentrations monitored with this method correlated well with the therapeutic response in dry eye patients.</div></div><div><h3>Conclusions</h3><div>This study developed Eu-TRFICO Schirmer strips with high sensitivity, specificity, precision, and satisfactory clinical testing performance, which provides a convenient and quantitative option for clinical testing of tear MMP-9 in dry eye patients.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 119-125"},"PeriodicalIF":5.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019449","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}

{"title":"Destructive and protective effects and therapeutic targets of IL-36 family cytokines in dry eye disease","authors":"Xin Chen ,&nbsp;Na Lin ,&nbsp;Haixia Liu ,&nbsp;Jing Lin ,&nbsp;Ning Gao ,&nbsp;Zhao Liu ,&nbsp;Cintia S. de Paiva ,&nbsp;Stephen C. Pflugfelder ,&nbsp;De-Quan Li","doi":"10.1016/j.jtos.2025.01.003","DOIUrl":"10.1016/j.jtos.2025.01.003","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore the destructive and protective effects and therapeutic targets of IL-36 cytokines in dry eye disease using a murine dry eye model.</div></div><div><h3>Methods</h3><div>A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls. A topical challenge model was performed in normal mice with exogenous rmIL-36α, rhIL-38 and 2 % ectoine, or PBS vehicle. IL-36 cytokine expression was assessed by RT-qPCR and immunofluorescent (IF) staining. Corneal epithelial damage was evaluated by corneal smoothness score, Oregon Green Dextran (OGD) fluorescent staining, and tight junction barrier.</div></div><div><h3>Results</h3><div>All members of the IL-36 family were expressed by murine ocular surface epithelium. The expression of IL-36α and IL-36γ was upregulated while IL-38 and IL-36RN were down regulated in ocular surface of dry eye mice. A topical challenge of rmIL-36α directly destructed corneal surface with distorted smoothness, increased OGD uptake and IF intensity, and disrupted tight junction proteins ZO-1 and occludin. Co-application with rhIL-38 prevented all these corneal damages by rmIL-36α. Ectoine treatment reversed the pathological expression pattern of IL-36 cytokines, protected corneal epithelium from defects, and restored the tight junction barrier in DS mice, and even prevented corneal damage by rmIL-36α.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate the upregulated pro-inflammatory agonists IL-36α and IL-36γ with downregulated antagonists IL-38 and IL-36RA in dry eye model, which provides a previously unknown mechanism and therapeutic targets in dry eye disease. The therapeutic efficacy of ectoine may be through reversing the pathological alteration of IL-36 cytokines in dry eye mice.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 83-93"},"PeriodicalIF":5.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974248","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}

{"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,&nbsp;Pratima Krishna Suvas,&nbsp;Mashidur Rana,&nbsp;Anish Chakraborty,&nbsp;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":"2025-01-08","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}