Ocular Surface最新文献

{"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}

{"title":"Mechanoreceptor Piezo1 channel-mediated interleukin expression in conjunctival epithelial cells: Linking mechanical stress to ocular inflammation","authors":"Seiya Fukuoka ,&nbsp;Naoki Adachi ,&nbsp;Erika Ouchi ,&nbsp;Hideshi Ikemoto ,&nbsp;Takayuki Okumo ,&nbsp;Fumihiro Ishikawa ,&nbsp;Hidetoshi Onda ,&nbsp;Masataka Sunagawa","doi":"10.1016/j.jtos.2025.01.001","DOIUrl":"10.1016/j.jtos.2025.01.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Mechanical stress on the ocular surface, such as from eye-rubbing, has been reported to lead to inflammation and various ocular conditions. We hypothesized that the mechanosensitive Piezo1 channel in the conjunctival epithelium contributes to the inflammatory response at the ocular surface after receiving mechanical stimuli.</div></div><div><h3>Methods</h3><div>Human conjunctival epithelial cells (HConjECs) were treated with Yoda1, a Piezo1-specific agonist, and various allergens to measure cytokine expression levels using qRT-PCR. Piezo1 activation-induced intracellular signaling pathways were also investigated by Western blot. Mechanical stretching experiments were conducted to simulate Piezo1 activation in HConjECs. Specificity of Piezo1 was confirmed by <em>PIEZO1</em> knockdown and GsMTx4. In <em>in vivo</em> studies, using immunohistochemistry, rats were administered Yoda1 eye drops to examine the inflammatory response in the conjunctiva and Piezo1-induced signaling activation.</div></div><div><h3>Results</h3><div>HConjECs expressed functional Piezo1 channel which was the dominant mechanoreceptor among putative channels and whose activation significantly increased <em>IL-6</em> and <em>IL-8</em> expression through the p38 MAPK-CREB pathway. Piezo1-induced [Ca²⁺]_i elevation was crucial for the production of IL-6. The Yoda1-induced inflammatory responses were blocked by <em>PIEZO1</em> knockdown. Mechanical stretching mimicked these effects, which were suppressed by GsMTx4. <em>In vivo</em>, Yoda1 administration led to increased phospho-p38 MAPK, phospho-CREB, and IL-6 in the rat conjunctival epithelium, with significant neutrophil infiltration.</div></div><div><h3>Conclusion</h3><div>Mechanical stress-induced Piezo1 channel activation in conjunctival epithelial cells can cause ocular inflammation by upregulating pro-inflammatory cytokines via the p38 MAPK-CREB pathway and promoting neutrophil infiltration. These findings suggest that mechanical stimuli on ocular surface tissues are significant risk factors for ocular inflammation.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"36 ","pages":"Pages 56-68"},"PeriodicalIF":5.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960920","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":"Matrix glycosaminoglycans and proteoglycans in human cornea organoids and similarities with fetal corneal stages","authors":"Sean Ashworth ,&nbsp;Manas Dhanuka ,&nbsp;Alireza Khodadadi-Jamayran ,&nbsp;Madhuri Amulya Koduri ,&nbsp;George Maiti ,&nbsp;Shukti Chakravarti","doi":"10.1016/j.jtos.2024.11.007","DOIUrl":"10.1016/j.jtos.2024.11.007","url":null,"abstract":"<div><h3>Purpose</h3><div>We developed human cornea organoids (HCOs) from induced pluripotent stem cells (iPSCs) where single-cell RNA-sequence (scRNA-seq) analysis suggested similarity with developing rather than mature human corneas. We performed immunohistology to determine the presence of corneal glycosaminoglycans as an assessment of maturity.</div><div>We undertook a detailed comparison of the HCO scRNA-seq data with a recent scRNA-seq study of human fetal corneas at different stages to gauge the HCO's maturity.</div></div><div><h3>Methods</h3><div>We generated HCOs from a second iPSC line, NCRM-1, to assess the reproducibility of HCO development. We stained sections from both HCO lines with Alcian blue and picrosirius red to determine deposition of sulfated glycosaminoglycans and fibrillar collagens. We immunolocalized glycosaminoglycan biosynthetic enzymes and proteoglycan core proteins. The scRNA-seq data from IMR90.4 HCOs were compared to that of fetal corneas using MetaNeighbor analysis to assess the similarity of HCOs to different stages of human corneal development.</div></div><div><h3>Results</h3><div>The MetaNeighbor analysis suggests closer alignment of the IMR90.4 HCOs with 17–18 post-conception week fetal human corneas. HCOs from both iPSC lines deposit sulfated glycosaminoglycans and fibrillar collagens. Immunohistology showed chondroitin/dermatan sulfate (CS/DS) and keratan sulfate in the presumptive stromal and some epithelial layers. The NCRM-1-derived HCOs show increased CS/DS staining compared to the IMR90.4 derived HCOs.</div></div><div><h3>Conclusions</h3><div>Both HCO lines show similar developmental patterns and timeline. The NCRM-1 HCO line may have more glycosaminoglycan deposition. Overall, the glycosaminoglycan deposition pattern is consistent with an immature tissue. Optimizations based on our current findings may yield more mature stromal cells and cornea-typical proteoglycans.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"35 ","pages":"Pages 68-80"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776153","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}