Ocular Surface最新文献

{"title":"Inhibition of H3K14 lactylation promotes diabetic corneal nerve regeneration via Wnt1/β-catenin signaling","authors":"Wenqu Chen ,&nbsp;Yuyang Deng ,&nbsp;Danling Liao ,&nbsp;Jianzhang Hu","doi":"10.1016/j.jtos.2026.01.008","DOIUrl":"10.1016/j.jtos.2026.01.008","url":null,"abstract":"<div><h3>Aims</h3><div>This study bridges diabetes-induced metabolic alterations and corneal neuropathy, proposing lactylation as a key mechanistic and therapeutic target in diabetic keratopathy (DK).</div></div><div><h3>Methods</h3><div>We used a streptozotocin-induced Type 1 diabetes mellitus (T1DM) mouse model to examine metabolic reprogramming in trigeminal ganglion (TG) neurons and its effects on corneal nerve regeneration. Glycolysis, lactate levels, and histone lactylation (H3K14la) were analyzed via Western blot, qPCR, immunofluorescence, and enzymatic assays. Genome-wide H3K14la profiling was conducted using CUT&amp;Tag, followed by KEGG pathway analysis. Functional studies involved AAV-mediated gene modulation to evaluate lactate and Wnt1/β-catenin signaling roles, with outcomes assessed by corneal sensitivity tests, epithelial wound healing assays, and β-tubulin III–based nerve density quantification.</div></div><div><h3>Results</h3><div>T1DM mice exhibited enhanced glycolysis in TG neurons, elevated lactate levels, and increased H3K14la enrichment, particularly at the Wnt1 promoter. CUT&amp;Tag revealed genome-wide upregulation of H3K14la peaks, with significant enrichment in the Wnt signaling pathway. Elevated H3K14la repressed Wnt1 transcription, leading to suppression of the Wnt1/β-catenin pathway and downregulation of regenerative targets cyclin D1 and c-myc. LDHA knockdown reduced lactate and H3K14la levels, restored Wnt1/β-catenin activity, and promoted corneal nerve regeneration and wound healing, whereas LDHA overexpression exacerbated deficits. Wnt1 overexpression rescued corneal nerve function in diabetic mice, while Wnt1 knockdown abolished the benefits of LDHA suppression.</div></div><div><h3>Conclusions</h3><div>Hyperglycemia-driven glycolysis increases lactate-mediated H3K14la at the Wnt1 promoter, repressing Wnt1/β-catenin signaling and impairing corneal nerve regeneration. Targeting lactate metabolism or histone lactylation represents a promising therapeutic strategy for DK.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 40-51"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109943","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":"Progranulin restores diabetic corneal healing by modulating NF-κB–Driven inflammation and neuro-regenerative pathways","authors":"Tianyi Zhou ,&nbsp;Yuchen Cai ,&nbsp;Jiaming Sun ,&nbsp;Fei Fang ,&nbsp;Hao Sun ,&nbsp;Yao Fu","doi":"10.1016/j.jtos.2026.02.006","DOIUrl":"10.1016/j.jtos.2026.02.006","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic keratopathy is characterized by delayed epithelial healing and reduced corneal nerve density, however effective treatment remains a significant challenge. Progranulin (PGRN), a secreted anti-inflammatory and neuroprotective factor, has been implicated in ocular homeostasis, but its role in the cornea has not been well defined.</div></div><div><h3>Objective</h3><div>To investigate the function of PGRN in corneal repair under normal and diabetic conditions and to identify underlying mechanisms.</div></div><div><h3>Methods</h3><div>PGRN expression in normal and diabetic mouse corneas was assessed by Western blot, ELISA, and immunohistochemistry. Corneal epithelial debridement models were established in normoglycemic, diabetic, and <em>GRN</em>-KO mice, followed by topical PGRN treatment. Epithelial healing and nerve regeneration were evaluated. In addition, inflammatory cytokines, neurotrophic factors, and transcriptomic changes were assessed in <em>GRN</em>-KO mice.</div></div><div><h3>Results</h3><div>PGRN was found significantly reduced in diabetic corneas, and topical exogenous PGRN accelerated epithelial closure and nerve regrowth in normal and diabetic mice. <em>GRN</em>-KO mice exhibited delayed healing and impaired nerve regeneration after wounding. RNA-seq revealed enrichment of neuroinflammation related pathways. <em>GRN</em>-KO corneas showed increased NF-κB activation and elevated IL-1β, IL-6, and TNF-α levels, whereas PGRN supplementation suppressed these inflammatory responses and enhanced IL-10, Arg-1, and NGF expression.</div></div><div><h3>Conclusion</h3><div>PGRN is essential for maintaining corneal epithelial–neural–immune homeostasis. Its deficiency reproduces key features of diabetic keratopathy, while exogenous PGRN promotes repair and reduces neuroinflammation, supporting its potential as a therapeutic target.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 105-116"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160447","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":"Australasian consensus recommendations on stem cell therapies for managing ocular surface diseases","authors":"Rhys J.P. Skelton ,&nbsp;Himal Kandel ,&nbsp;Maria Cabrera-Aguas ,&nbsp;Nick Di Girolamo ,&nbsp;Fred K. Chen ,&nbsp;Alice Pébay ,&nbsp;Stephanie L. Watson","doi":"10.1016/j.jtos.2026.02.004","DOIUrl":"10.1016/j.jtos.2026.02.004","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 86-88"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160449","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":"Serum inflammatory biomarkers in ocular pemphigoid closely resemble that of dry eye disease: A cross-sectional study","authors":"Yulu Wang ,&nbsp;Adrian P. Mansini ,&nbsp;Jing Li ,&nbsp;Haley Gainer ,&nbsp;Claudia Lasalle ,&nbsp;Sanjana Chandran ,&nbsp;Sumaiya Shahjahan ,&nbsp;Hajirah N. Saeed ,&nbsp;Ali Djalilian ,&nbsp;Kyle T. Amber","doi":"10.1016/j.jtos.2026.01.004","DOIUrl":"10.1016/j.jtos.2026.01.004","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 9-11"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014639","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":"High-resolution high-contrast in vivo phase imaging of corneal nerves and immune cells in mice","authors":"Suil Jeon ,&nbsp;Noseong Park ,&nbsp;Seong Han Kim ,&nbsp;Chang Ho Yoon ,&nbsp;Kyoung Woo Kim ,&nbsp;Ki Hean Kim","doi":"10.1016/j.jtos.2026.01.009","DOIUrl":"10.1016/j.jtos.2026.01.009","url":null,"abstract":"<div><h3>Purpose</h3><div>Interactions between corneal nerves and immune cells are essential for corneal homeostasis and inflammation regulation. Although simultaneous imaging has been demonstrated, existing in vivo techniques often provide limited contrast for resolving fine cellular morphology. This study evaluates a label-free, high-resolution phase contrast microscopy approach for simultaneous visualization of corneal nerves and immune cells in mouse model.</div></div><div><h3>Methods</h3><div>A high-resolution differential phase contrast (DPC) microscopy system was developed using highly angled oblique illumination and a high numerical aperture objective. The system was applied to mouse corneas (<em>n</em> = 5) before and 6 h after partial circular corneal nerve cut (CNC). Three-dimensional and time-lapse imaging were performed and compared with in vivo confocal microscopy (IVCM). Immunofluorescence (IF) imaging of ex vivo corneas provided structural validation. Immune cell density in the central cornea was quantified before and after injury.</div></div><div><h3>Results</h3><div>DPC microscopy enabled clear visualization of the sub-basal nerve plexus (SBNP) and cellular structures in naïve corneas. Compared with IVCM, DPC provided more continuous visualization of nerve fibers and revealed fine immune cell structures based on refractive index variation. Following CNC, reduced visibility of SBNP fibers and an increase in cell density were observed, from 50 ± 18 to 226 ± 59 cells/mm². Time-lapse DPC imaging enabled distinction of cells with intracellular activity. Structural features observed with DPC imaging were corroborated by IF imaging.</div></div><div><h3>Conclusions</h3><div>High-resolution DPC microscopy enables label-free visualization of corneal nerves and immune cells with improved structural continuity compared with conventional IVCM. This approach provides a versatile platform for studying corneal neuro-immune interactions, with further development, may support translational research and clinical diagnostics.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 63-70"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109944","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":"Lacrimal gland duct obstruction and dacryops: Unravelling its pathogenesis with proteomics and cellular profiling","authors":"Swati Singh","doi":"10.1016/j.jtos.2026.01.007","DOIUrl":"10.1016/j.jtos.2026.01.007","url":null,"abstract":"<div><h3>Purpose</h3><div>To understand the pathogenesis of the main lacrimal gland dacryops (ductular cyst) using proteomics and cellular profiling.</div></div><div><h3>Methods</h3><div>Four patients (mean age, 42.2 ± 18.4 years) with dacryops underwent cyst excision following the aspiration of the cyst contents. Cyst contents were processed using mass spectrometry and compared with eight healthy tear samples. The cyst wall was processed for histology (H&amp;E, Masson trichrome), epithelial (Aquaporin 5, CK15, CK19), stromal (Vimentin), neural (beta-III tubulin, NCAM), and immune cell markers (CD3, CD20, CD138, myeloperoxidase, CD68).</div></div><div><h3>Results</h3><div>The cyst lining was cuboidal to squamous in three cases (CK19+, ductal origin), and exhibited goblet cell metaplasia in one case. Compared to normal ducts, the dacryops cyst wall lacked expression of AQP5 and beta-III tubulin. Subepithelial fibrosis and strong vimentin positivity were observed in all specimens, along with mild to moderate inflammation. Infiltrating immune cells were CD20⁺ and CD138+, with a few macrophages and neutrophils noted perivascularly. The visible few lacrimal gland acini within the cyst wall showed inflammation, IgA-positive plasma cells, and focal acinar atrophy. The cyst fluid and tear samples were widely separated on the PCA plot, with 190 proteins upregulated and 52 downregulated. The upregulated proteins were involved in immunoglobulin-mediated immune responses, complement activation, apolipoproteins, extracellular matrix components (including matrix metalloproteinases 7 and 10), and glycosaminoglycan binding.</div></div><div><h3>Conclusion</h3><div>Dacryops involves reactive ductular ectasia secondary to inflammation, resulting in increased MMPs, fibrosis, and loss of the periductal neural network. The cyst fluid is rich in apolipoproteins, immunoglobulins, and complement factors. Future research could focus on the lipidomics of the cyst fluid.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 31-39"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072211","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":"Video frame rate influences the accuracy of blink dynamics measurement","authors":"Maria Navascues-Cornago,&nbsp;Carole Maldonado-Codina,&nbsp;Philip B. Morgan,&nbsp;Michael L. Read","doi":"10.1016/j.jtos.2026.01.003","DOIUrl":"10.1016/j.jtos.2026.01.003","url":null,"abstract":"<div><h3>Purpose</h3><div>High-speed imaging is required to capture the rapid eyelid motion during blinking. However, the minimum frame rate necessary for accurate measurement remains unclear. This study investigated how video frame rate affects the accuracy of blink metrics.</div></div><div><h3>Methods</h3><div>Spontaneous blinks were recorded in 20 participants and reflex blinks were recorded in an additional 10 participants using a 500 frames per second (fps) high-speed infrared camera. Videos were downsampled to simulate acquisition at 250, 100, 50 and 25 fps. Blink metrics were extracted at each frame rate: average and maximum closing/opening velocities, closed-phase duration, total duration, and amplitude. Percentage differences from the 500-fps reference were calculated and agreement was assessed using Bland-Altman analysis with limits of agreement (LoA).</div></div><div><h3>Results</h3><div>Agreement with the 500-fps reference varied across metrics. Blink amplitude and duration showed minimal bias and narrow LoA across all frame rates. In contrast, velocity metrics were underestimated at low frame rates, particularly for maximum velocities and reflex blinks. For spontaneous blinks, average closing velocity showed good agreement at 100–250 fps, whereas for reflex blinks, only 250 fps achieved comparable measurements. Average opening velocity was less sensitive to frame rate, with ≥50 fps showing minimal bias. Maximum velocities were markedly underestimated below 250 fps for both blink types.</div></div><div><h3>Conclusion</h3><div>Video frame rate significantly impacts the accuracy of certain blink metrics. Low frame rates may be sufficient for estimating blink amplitude and duration, while velocity metrics require higher sampling. A minimum of 250 fps is recommended for a comprehensive assessment of blink dynamics.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 22-30"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000890","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":"Paediatric Acanthamoeba keratitis: Risk factors, clinical features and treatment outcomes","authors":"A.L. Milligan ,&nbsp;C.B.J. Ashton ,&nbsp;A.C. Randag ,&nbsp;D.F.P. Larkin","doi":"10.1016/j.jtos.2026.01.002","DOIUrl":"10.1016/j.jtos.2026.01.002","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 5-8"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956642","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 comprehensive review of tear fluid proteome alterations in dry eye disease: Insights into pathophysiology and biomarker potential","authors":"Saleh Ahmed ,&nbsp;Steven Safille ,&nbsp;Victoria Clifton ,&nbsp;Shruti Sharma ,&nbsp;Cintia S. de Paiva ,&nbsp;Ashok Sharma","doi":"10.1016/j.jtos.2026.01.010","DOIUrl":"10.1016/j.jtos.2026.01.010","url":null,"abstract":"<div><div>Tear fluid is a highly specialized and dynamic biofluid composed of proteins, lipids, mucins, and electrolytes that is essential for maintaining ocular surface integrity, immune defense, and tear film stability. Growing evidence from tear proteomic studieshas revealed extensive alterations in protein composition in dry eye disease (DED), reflecting a complex interplay between local ocular surface pathology and systemic inflammatory influences. This review summarizes proteomic findings from 50 published studies to identify tear proteins that are consistently upregulated or downregulated in DED and to interpret their biological relevance in the context of ocular surface homeostasis.</div><div>Across studies, proteins upregulated in DED tears predominantly reflect activation of acute-phase and inflammatory pathways, including S100A8/A9, ORM1, APOA2, and proinflammatory cytokines, as well as oxidative stress responses and epithelial remodeling processes. In contrast, downregulated proteins include key protective and homeostatic tear components such as lactoferrin, lysozyme, lipocalin-1, lacritin, and secretoglobins, along with proteins involved in immune transport, epithelial structure, and lipid metabolism that are critical for tear film stability. Overall, these proteomic shifts indicate activation of stress and inflammatory pathways that may perpetuate epithelial barrier damage and tear film instability in DED.</div><div>By integrating proteomic data across diverse methodologies, this review highlights convergent biological pathways underlying DED pathophysiology and suggests the potential of tear-based protein panels as biomarkers for disease stratification, monitoring, and therapeutic targeting.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 71-85"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109938","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":"Pipeline: Pharmacotherapy of dry eye disease in vertebrates","authors":"Gary D. Novack ,&nbsp;Sara M. Thomasy ,&nbsp;Brian Leonard","doi":"10.1016/j.jtos.2025.10.005","DOIUrl":"10.1016/j.jtos.2025.10.005","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"39 ","pages":"Pages 79-81"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461311","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}