Ocular Surface最新文献

{"title":"Metabolic reprogramming in lacrimal gland GVHD: Stage-specific shifts in acinar cells as drivers of disease progression","authors":"Kaifeng Jin ,&nbsp;Ning Wang ,&nbsp;Chongyang Mou ,&nbsp;Kelan yuan ,&nbsp;Chunyang Wang ,&nbsp;Jiajia Yuan ,&nbsp;Fang Zheng ,&nbsp;Zhi Fang ,&nbsp;Xiuming Jin ,&nbsp;Jingliang He ,&nbsp;Qingqing Wang ,&nbsp;Shuo Yang","doi":"10.1016/j.jtos.2026.02.003","DOIUrl":"10.1016/j.jtos.2026.02.003","url":null,"abstract":"<div><h3>Purpose</h3><div>Ocular graft-versus-host disease (oGVHD) progresses through inflammatory and fibrotic phases, yet the temporal dynamics of the lacrimal gland (LG) cellular ecosystem remain unclear. This study aims to delineate the phase-specific alterations driving oGVHD pathogenesis.</div></div><div><h3>Methods</h3><div>We performed integrated single-cell RNA sequencing on murine LGs at acute (7-day) and chronic (28-day) GVHD stages. Transcriptional profiling was combined with pseudotime trajectory analysis, computationally inferred cell-cell communication networks, and immunofluorescence validation.</div></div><div><h3>Results</h3><div>Temporal analysis revealed extensive phase-specific cellular reprogramming. Acute GVHD was characterized by expansion of globulin-specific acinar cells with altered glycan metabolism, alongside inflammatory fibroblasts predicted to license cytotoxic T-cell responses via H2-k1-Cd8 interactions. Chronic GVHD featured metabolic diversification of acinar subtypes, including upregulated N-glycan biosynthesis in lipid-associated cells and activated α-linolenic acid metabolism in water/electrolyte-secreting cells, along with emergent myeloid-epithelial crosstalk. Computational analyses identified novel ligand-receptor pairs, suggesting plasmacytoid dendritic cells engage water/electrolyte-secreting acinar cells via Gm-Sort1, and mast cells target lipid-associated subtypes via Ptprc-Cd22. Infiltration of pDCs and mast cells was validated by immunofluorescence. Trajectory analysis indicated acinar plasticity reflects environment-instructed adaptation rather than hierarchical differentiation.</div></div><div><h3>Conclusions</h3><div>These results define a phase-shift mechanism in oGVHD: acute damage involves a fibroblast–T cell–epithelium triad, while chronic dysfunction is driven by acinar metabolic reprogramming and myeloid-mediated epithelial dysregulation. Our temporal single-cell atlas integrates computational predictions with morphological validation to reveal stage-specific therapeutic targets for intervening in disease progression.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 89-104"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152651","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":"Cattle to Cornea: A series of C. bovis eye cultures","authors":"Carla G. Dias ,&nbsp;Tobin B.T. Thuma ,&nbsp;Jamie Marino ,&nbsp;Matthew S. Simon ,&nbsp;Grace Sun","doi":"10.1016/j.jtos.2026.01.001","DOIUrl":"10.1016/j.jtos.2026.01.001","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 1-4"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950133","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":"IL-24 regulates corneal inflammation and fibrosis in fungal keratitis via the caspase-11/gasdermin D pathway","authors":"Hua Yang ,&nbsp;Wenting Liu ,&nbsp;Dawei Zhang ,&nbsp;Qiang Xu ,&nbsp;Jieun Lee ,&nbsp;Jintao Sun ,&nbsp;Shasha Xue ,&nbsp;Xiaoyan Sun ,&nbsp;Chengye Che","doi":"10.1016/j.jtos.2026.01.005","DOIUrl":"10.1016/j.jtos.2026.01.005","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate the role of interleukin-24 (IL-24) in the inflammatory response and repair of corneal damage caused by fungal keratitis (FK).</div></div><div><h3>Methods</h3><div>Mouse model was infected with <em>Aspergillus fumigatus</em> (<em>A. fumigatus</em>) to induce FK. An <em>in vitro</em> model was established by stimulating THP-1 cells and human corneal epithelial cells (HCECs) with <em>A. fumigatus</em> spores. IL-24 expression was inhibited by small interfering RNA (siRNA). The production and role of IL-24 in FK were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence, clinical scoring, anterior segment optical coherence tomography (OCT), hematoxylin and eosin (HE) staining, confocal corneal microscopy, and myeloperoxidase (MPO) assays.</div></div><div><h3>Results</h3><div>IL-24 expression was increased in mouse models of FK, fungal-stimulated THP-1 macrophages, and HCECs compared to controls. Compared to controls, siRNA inhibition of IL-24 reduced the inflammatory response, corneal edema, and neutrophil and macrophage recruitment within the corneal stroma. In <em>A. fumigatus</em>-infected keratitis, IL-24 production was induced by hypoxia-inducible factor-1α (HIF-1α). Tumor necrosis factor-α (TNF-α), IL-6, and IL-10 were inflammatory factors regulated by IL-24, which played a role in pyroptosis via the caspase-11/gasdermin D (GSDMD) pathway. Inhibition of IL-24 attenuated corneal neovascularization and fibrosis during long-term FK in mice.</div></div><div><h3>Conclusions</h3><div>This study demonstrated the important role of IL-24 in corneal antifungal immunity. In <em>A. fumigatus</em>-infected keratitis, IL-24 might be crucial for the recruitment of inflammatory cells, induction of cellular pyroptosis, and production of inflammatory cytokines. Furthermore, IL-24 is also involved in the development of fibrosis during corneal repair.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 12-21"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014777","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: The next generation of therapy for ocular surface disease","authors":"Gary D. Novack","doi":"10.1016/j.jtos.2025.12.004","DOIUrl":"10.1016/j.jtos.2025.12.004","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 274-275"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893580","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":"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":"Investigating conjunctival immune pathways in Sjögren and non-Sjögren disease associated dry eye","authors":"Kaitlin K. Scholand ,&nbsp;Laura Schaefer ,&nbsp;Jianming Shao ,&nbsp;Zhiyuan Yu ,&nbsp;Stephen C. Pflugfelder ,&nbsp;Robert A. Britton ,&nbsp;Cintia S. de Paiva","doi":"10.1016/j.jtos.2026.02.001","DOIUrl":"10.1016/j.jtos.2026.02.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Dry eye disease (DED) is classified based on its predominant etiology into aqueous tear-deficient (ATD), evaporative, or mixed. Sjӧgren disease keratoconjunctivitis sicca (SjD-KCS) is a very severe autoimmune form of ATD DED. The purpose of this work was to compare transcriptomic changes in the conjunctiva sampled from patients with ATD, SjD-KCS, and healthy controls (HC) to evaluate distinctions in the immune response on the ocular surface based on diagnosis.</div></div><div><h3>Methods</h3><div>Impression cytology of the temporal bulbar conjunctiva was collected using the EyePrim device. RNA was extracted and submitted with the Nanostring nCounter Human Immunology V2 panel for gene expression analysis. Results were uploaded to ROSALIND and Metascape to identify DEGs by comparison (all DED vs HC; SjD vs HC; ATD vs HC) and associated predicted pathways. A subset of samples (n = 4 per group) were used for immunofluorescent staining of LAMP3 and HLA-DR.</div></div><div><h3>Results</h3><div>49 patients were enrolled in the study (25 HC; 12 SjD; 12 ATD). 100 DEGs were found in the comparison of all DED vs HC. 69 DEGs were found in the SjD vs HC. 11 DEGs were found in the ATD vs HC. There were no DEGs identified in the SjD vs ATD comparison. DEGs were involved in immune pathways related to viral response, adaptive immunity, and cell to cell communication. DED conjunctiva had increased expression of LAMP3 and HLA-DR compared to HC.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that DED, regardless of the diagnosis, have similar immune-related DEGs and associated pathways on the ocular surface.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"40 ","pages":"Pages 52-62"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133782","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}