Ocular SurfacePub Date : 2025-05-30DOI: 10.1016/j.jtos.2025.05.010
Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu
{"title":"Fenofibrate ameliorates ocular surface inflammation in diabetic keratopathy","authors":"Hassan Mansoor , Isabelle Xin Yu Lee , Chang Liu , Mingyi Yu , Charmaine Jan Li Toh , Victor Wei-Tsu Hsu , Fengyi Liu , Daqian Lu , Thomas Chuen Lam , Hong Chang Tan , Lei Zhou , Yu-Chi Liu","doi":"10.1016/j.jtos.2025.05.010","DOIUrl":"10.1016/j.jtos.2025.05.010","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the efficacy of oral fenofibrate in the amelioration of ocular surface inflammation in diabetes mellitus (DM).</div></div><div><h3>Methods</h3><div>In this open-label interventional study, 41 participants with type 2 DM received oral fenofibrate for 30 days. Forty age-matched healthy controls were recruited. Ocular surface objective and subjective assessment, in-vivo confocal microscopy (IVCM) imaging and quantification for corneal dendritic cells (DCs), epithelium and neuromas were performed. Tear inflammatory markers and proteomics were analyzed with enzyme-linked immunosorbent assay (ELISA) and Data Independent Acquisition experiments before and after treatment.</div></div><div><h3>Results</h3><div>Oral fenofibrate treatment significantly improved tear film breakup time (p = 0.004), corneal staining evaluated with National Eye Institute-Corneal Fluorescein Staining scores (p = 0.005), and ocular surface symptoms assessed with the Ocular Surface Disease Index scores (p = 0.003), in DM patients. On IVCM, fenofibrate significantly reduced mean DC area (p = 0.01) and mean DC density (p = 0.02), while increasing mean DC elongation (p = 0.004) and length (p = 0.01), suggesting less DC activities. Fenofibrate also significantly increased corneal epithelial cell density (p = 0.04). 192 tear proteins were significantly altered after treatment. Fenofibrate significantly up-regulated the expression of anti-inflammatory interleukin-1 receptor antagonist, while significantly reduced the concentrations of pro-inflammatory and inflammatory proteins, including tumour necrosis factor α, nuclear factor kappa B, complement 4 B, cytochrome B5 Type A, and cytochrome B5 Type B (all p < 0.05) in tears, via regulation of tricarboxylic acid cycle, oxidative phosphorylation and liver X receptor/retinoid X receptor activation.</div></div><div><h3>Conclusion</h3><div>This first clinical trial demonstrated that oral fenofibrate ameliorates diabetic ocular surface inflammation, providing a novel therapeutic option for diabetic keratopathy.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 31-40"},"PeriodicalIF":5.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195330","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}
Ocular SurfacePub Date : 2025-05-23DOI: 10.1016/j.jtos.2025.05.009
Grace C. Tu , Farshad Abedi , Arthur Y. Chang , Xiang Shen , Mohammad Soleimani , Iskra Araujo , Rebecca Jung , Jeonghyun Kwon , Khandeker N. Anwar , Zohreh Arabpour , Nadim Mahmud , Elmer Y. Tu , Reza Dana , Peiman Hematti , Charlotte E. Joslin , Ali R. Djalilian
{"title":"Safety of subconjunctival injection of mesenchymal stromal cells in persistent corneal epithelial disease – A phase 1b clinical trial","authors":"Grace C. Tu , Farshad Abedi , Arthur Y. Chang , Xiang Shen , Mohammad Soleimani , Iskra Araujo , Rebecca Jung , Jeonghyun Kwon , Khandeker N. Anwar , Zohreh Arabpour , Nadim Mahmud , Elmer Y. Tu , Reza Dana , Peiman Hematti , Charlotte E. Joslin , Ali R. Djalilian","doi":"10.1016/j.jtos.2025.05.009","DOIUrl":"10.1016/j.jtos.2025.05.009","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the safety and tolerability of subconjunctival injection of three escalating doses of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in patients with persistent corneal epithelial defect/disease (PCED).</div></div><div><h3>Design</h3><div>Prospective single-center open label phase 1b clinical trial.</div></div><div><h3>Participants</h3><div>Patients with PCED in the setting of neurotrophic keratitis and/or limbal stem cell deficiency.</div></div><div><h3>Methods</h3><div>A dose escalation study design was used. The first three patients received a subconjunctival injection of 1 × 10<sup>6</sup> MSCs/50 μL suspension; subsequently, three participants were treated with 1 subconjunctival injection of 3 × 10<sup>6</sup> MSCs/150 μL; and two participants received 2 subconjunctival injections of 3 × 10<sup>6</sup> MSCs/150 μl in 2 conjunctival sites.</div></div><div><h3>Main outcome measures</h3><div>The primary outcome was the safety of the treatment determined on day 28 post-injection. Ocular surface toxicity and other ocular or systemic treatment emergent adverse events (TEAEs) were assessed at 1, 7, 14, 28 and 90 days. Demonstration of safety on day 28 was required before escalating to the next higher dose. Changes in the PCED were also monitored.</div></div><div><h3>Results</h3><div>Eight participants completed the 90-day study. All 3 doses of subconjunctival MSCs were well tolerated. No participant developed ocular surface toxicity or other ocular or systemic TEAEs. The size of the PCED improved in 5 (63 %) patients; it increased in 2 (25 %) patients; and no progressive improvement was observed with dose escalation.</div></div><div><h3>Conclusion</h3><div>Subconjunctival administration of MSCs was safe and well tolerated with no systemic or ocular toxicity in patients with PCED. Improvement in epithelial defect size was observed in 63 % of the participants.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 8-13"},"PeriodicalIF":5.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145335","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}
Ocular SurfacePub Date : 2025-05-22DOI: 10.1016/j.jtos.2025.05.007
Liangbo Chen , Shiding Li , Yao Fu
{"title":"MicroRNAs in corneal Diseases: Emerging roles as biomarkers, regulators, and therapeutics","authors":"Liangbo Chen , Shiding Li , Yao Fu","doi":"10.1016/j.jtos.2025.05.007","DOIUrl":"10.1016/j.jtos.2025.05.007","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in regulating gene expression. Emerging evidence suggests that miRNAs are closely involved in the pathophysiology of various corneal diseases, particularly in regulating corneal wound healing, inflammation and neovascularization. In this review, we summarized the recent progress of miRNAs in corneal diseases, especially focused on their application as diagnostic biomarkers, regulators of cell biology, and therapeutic targets. Recent advances in miRNA detection technology have made it possible to analyze minimal miRNAs in samples such as tears or exosomes, further enhancing the ability to identify disease-specific miRNA profiles and providing potential objective indicators for the early diagnosis of disease. Meanwhile, we summarized the mechanisms and pathways of multiple miRNAs in regulating various biological processes of corneal cells, as well as the advantages of studying miRNA compared to proteins or genes. Furthermore, we explore the potential of miRNAs-based therapies, especially introduce various miRNA delivery systems and challenges associated with clinical translation. This review highlights the need for further research to harness the full potential of miRNAs in treating various corneal diseases.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 14-30"},"PeriodicalIF":5.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145331","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}
Ocular SurfacePub Date : 2025-05-12DOI: 10.1016/j.jtos.2025.05.001
Natalie Phan , Yi Li , Menglu Yang , Fei Liu
{"title":"Tear fluid derived extracellular vesicles for new biomarker discovery","authors":"Natalie Phan , Yi Li , Menglu Yang , Fei Liu","doi":"10.1016/j.jtos.2025.05.001","DOIUrl":"10.1016/j.jtos.2025.05.001","url":null,"abstract":"<div><div>Various cell types release extracellular vesicles (EVs) containing proteins, DNA, and RNA essential for intercellular communication. The bioactive molecules from EVs can reflect disease status and monitor progression, while their communication abilities suggest therapeutic potential. We will review various EV isolation methods, EV-enriched fluids, and studies analyzing differential mi-RNA and protein levels extracted from EVs. Specifically, tear-derived EVs, which protect their molecular content and allow for real-time monitoring of ocular conditions such as Dry Eye Disease (DED), Sjögren's disease (SJD), Ocular graft-versus-host disease (oGVHD), and Diabetic Retinopathy (DR), which all currently remain undiagnosed in patients. EVs also provide potential as carriers for gene transfer, and mesenchymal stem cell (MSCs)-derived EVs are shown to be immunomodulatory, demonstrating promise for autoimmune ocular diseases. Through the multi-omic analysis of tear-fluid content, EVs are promising biomarkers and therapeutic agents in ocular diseases.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 314-322"},"PeriodicalIF":5.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082990","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}
Ocular SurfacePub Date : 2025-05-12DOI: 10.1016/j.jtos.2025.05.002
Celine Nguyen , Ebuka Eziama , Arturo R. Dominguez , Jennifer H. Cao
{"title":"Janus kinase inhibitors in the treatment of refractory cicatrizing conjunctivitis in pemphigoid","authors":"Celine Nguyen , Ebuka Eziama , Arturo R. Dominguez , Jennifer H. Cao","doi":"10.1016/j.jtos.2025.05.002","DOIUrl":"10.1016/j.jtos.2025.05.002","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy of Janus kinase inhibitor (JAKi) therapy in managing cicatrizing conjunctivitis associated with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid with ocular involvement (ocMMP).</div></div><div><h3>Methods</h3><div>Retrospective chart review of patients with cicatrizing conjunctivitis secondary to OCP or ocMMP who underwent treatment with JAKi at a tertiary academic medical center from August 2015 to November 2024 for minimum follow-up of six months. Collected data included demographics, Foster stage of cicatrization, and treatment course.</div></div><div><h3>Results</h3><div>Thirty-two patients met inclusion criteria: 23 (71.9 %) with OCP and 9 (28.1 %) with ocMMP. 96.9 % of patients demonstrated clinical improvement within twelve months of treatment initiation. Best response achieved were as follows: 1 (3.1 %) no response, 17 (53.1 %) partial response, 14 (43.8 %) complete remission, and 12 (37.5 %) steroid-free complete remission. The mean time to partial response, complete remission, steroid-free complete remission was 3.1 ± 1.8 (range, 0.9–8.3), 7.8 ± 3.3 months (range, 2.3–14.7 months), and 10.3 ± 7.4 months, (range, 2.3–31.4 months), respectively. Relapse in disease activity occurred in 8/32 (25.0 %) of patients. Side effects occurred in 8/32 (25.0 %) of patients. Four patients (12.5 %) discontinued therapy due to severe adverse events, including transient ischemic attack, pulmonary embolism, pyelonephritis, and cholecystitis. There was a significant association between lower Foster cicatrization stages and achieving remission (U = 630.0, p = 0.0036), with a rank-biserial correlation of 0.72.</div></div><div><h3>Conclusions</h3><div>JAK inhibitor therapy demonstrates efficacy in the management of recalcitrant cicatrizing conjunctivitis associated with pemphigoid. These findings highlight JAK inhibitors as a promising therapeutic option for refractory cases.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"38 ","pages":"Pages 1-7"},"PeriodicalIF":5.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082988","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":"Ranking the efficacy of topical treatments for ocular allergy: A network meta-analysis of current evidence","authors":"Luksanaporn Krungkraipetch , Taweelarp Tansavadi , Dechathorn Krungkraipetch","doi":"10.1016/j.jtos.2025.05.003","DOIUrl":"10.1016/j.jtos.2025.05.003","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate and rank the comparative effectiveness of topical treatments for different types of ocular allergies through a systematic review and network meta-analysis.</div></div><div><h3>Methods</h3><div>A systematic search of electronic databases identified between January 2000 and December 2024 from PubMed, Cochrane CENTRAL, Google Scholar, and Scopus databases. Study Selection; randomized controlled trials assessing topical treatments for ocular allergy, including antihistamines, corticosteroids, immunomodulators, and combination therapies. Data Extraction and Synthesis; data were independently extracted and analyzed following PRISMA guidelines. Direct and indirect comparisons were evaluated using network meta-analysis, and SUCRA rankings assessed relative efficacy. Main Outcomes and Measures; reduction in ocular itching, redness, and inflammation. PROSPERO Registration number: CRD42025634572.</div></div><div><h3>Results</h3><div>Olopatadine 0.1 % demonstrated highest efficacy in seasonal and perennial allergic conjunctivitis (SUCRA 0.88 and 0.85, respectively), while Tacrolimus 0.1 % showed superior effectiveness in vernal and atopic keratoconjunctivitis (SUCRA 0.92 and 0.89, respectively). Overall treatment effect was significant (OR = 6.95, 95 % CI: 6.24–7.75) with moderate heterogeneity (I<sup>2</sup> = 50.8 %). Subgroup analysis revealed consistent efficacy across different types of allergic conjunctivitis, with seasonal allergic conjunctivitis showing the highest cumulative ranking probability (89.0 %).</div></div><div><h3>Conclusions</h3><div>This network meta-analysis provides strong evidence supporting condition-specific treatment approaches in ocular allergies. Newer antihistamines, particularly Olopatadine, are most effective for mild-moderate conditions, while immunomodulators, especially Tacrolimus, show superior efficacy in severe cases. These findings provide clear evidence-based hierarchies for clinical decision-making in the management of different types of allergic conjunctivitis.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 273-282"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935169","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}
Ocular SurfacePub Date : 2025-05-08DOI: 10.1016/j.jtos.2025.05.005
Navid Fotovat-Ahmadi , Omer Siddiqui , Joshua Ong , Chanon Thanitcul , Christian Reinhardt , Stephanie M. Cologna , Vinay Kumar Aakalu
{"title":"The ocular surface tear film as a biomarker for systemic health","authors":"Navid Fotovat-Ahmadi , Omer Siddiqui , Joshua Ong , Chanon Thanitcul , Christian Reinhardt , Stephanie M. Cologna , Vinay Kumar Aakalu","doi":"10.1016/j.jtos.2025.05.005","DOIUrl":"10.1016/j.jtos.2025.05.005","url":null,"abstract":"<div><div>The tear film is a complex structure with rich interactions with the human body. A growing body of evidence suggests that measuring changes in protein, lipid, or other metabolite concentration in the tear film can be used to help detect disease. Particularly in the era of precision medicine, the tear film serves as a promising source of non-invasive insights into systemic health for early diagnosis and treatment. This paper analyzes the latest research in tear film biomarkers for systemic diseases. The review was conducted through PubMed and Embase databases using the PRISMA protocol and includes 54 articles. This paper first reviews the anatomy and physiology of tear film, as well as the latest proteomic analysis techniques on the tear film. We then provide a disease-by-disease review on the tear film as a biomarker including 5 articles related to Alzheimer's Disease, 10 articles related to Cancers, 1 article related to Cystic Fibrosis, 1 article related to Migraines, 4 articles related to Multiple Sclerosis, 15 articles related to Parkinson's Disease, 7 articles related to Rheumatoid Arthritis, and 11 articles related to Thyroid Disease. This paper highlights the promising results of these studies yet also reviews the challenges with limited sample sizes, reproducibility, and biological understanding of biomarkers. We conclude this paper with insights for future work to ensure clinical validity and generalizability. Ultimately, the tear film is a clinically accessible, complex structure that provides a wealth of information that may contribute to a more comprehensive understanding of systemic health.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 283-300"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942868","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}
Ocular SurfacePub Date : 2025-05-08DOI: 10.1016/j.jtos.2025.05.006
Ruize Shi , Mengyi Jin , Janbo Jin , Lina Xu , Zeyu Liu , Lan Zheng , Baihui Zeng , Kerui Wang , Xiang Li , Shurong Wang , Cheng Li
{"title":"Retinoic acid promotes conjunctival epithelium differentiation and goblet cell regeneration: evidence from novel 3D conjunctival organoids and whole-mount PAS staining","authors":"Ruize Shi , Mengyi Jin , Janbo Jin , Lina Xu , Zeyu Liu , Lan Zheng , Baihui Zeng , Kerui Wang , Xiang Li , Shurong Wang , Cheng Li","doi":"10.1016/j.jtos.2025.05.006","DOIUrl":"10.1016/j.jtos.2025.05.006","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the differentiation effects of retinoic acid on primary conjunctival epithelium using both 2D and 3D models, and to evaluate its <em>in vivo</em> effects on conjunctival epithelium and goblet cells in mice using a novel goblet cell assessment method.</div></div><div><h3>Methods</h3><div>The differentiation effects of retinoic acid were evaluated <em>in vitro</em> using 2D culture and 3D organoid models. Under 2D conditions, differentiation was assessed using qRT-PCR, light microscopy, immunofluorescence staining, and Western blot analysis for goblet cell markers. In the 3D organoid model, differentiation was confirmed using qRT-PCR, immunofluorescence staining, and AB-PAS staining. <em>In vivo</em>, a novel goblet cell assessment method—whole-mount PAS staining—was introduced, along with H&E staining to evaluate the effects of retinoic acid eye drops.</div></div><div><h3>Results</h3><div>In the 2D culture model, retinoic acid induced cell fusion, decreased stemness marker expression, and increased goblet cell differentiation markers. In the 3D organoid model, retinoic acid treatment led to elevated expression of goblet cell markers, including Muc5ac, Tff1, and Gcnt3, as confirmed by qRT-PCR, AB-PAS staining, and immunofluorescence. <em>In vivo</em>, retinoic acid eye drops promoted goblet cell generation, as demonstrated by the novel assessment method.</div></div><div><h3>Conclusions</h3><div>Retinoic acid promotes conjunctival epithelial differentiation and goblet cell regeneration both <em>in vitro</em> and <em>in vivo</em>. A novel method for goblet cell detection is proposed, providing a more accurate and reliable approach for evaluating conjunctival goblet cells in future research.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 301-313"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942870","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}
Ocular SurfacePub Date : 2025-05-07DOI: 10.1016/j.jtos.2025.05.004
Mayelín Pérez-Perdomo , Ana González-López , Laura Ortega-Llamas , David Alba-Molina , Mario Blanco-Blanco , María del Mar Granados , Adrián Guerrero-Moreno , Stephen Carl Pflugfelder , Christoph Ullmer , Sascha Fauser , Yolanda Jiménez-Gómez , Miguel González-Andrades
{"title":"Identification of a translatable animal model for dry eye disease using comparative analysis of tear proteins across species","authors":"Mayelín Pérez-Perdomo , Ana González-López , Laura Ortega-Llamas , David Alba-Molina , Mario Blanco-Blanco , María del Mar Granados , Adrián Guerrero-Moreno , Stephen Carl Pflugfelder , Christoph Ullmer , Sascha Fauser , Yolanda Jiménez-Gómez , Miguel González-Andrades","doi":"10.1016/j.jtos.2025.05.004","DOIUrl":"10.1016/j.jtos.2025.05.004","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).</div></div><div><h3>Methods</h3><div>Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.</div></div><div><h3>Results</h3><div>Among non-primate mammals, the cat (69.7 %) and pig (68.7 %) showed the highest protein sequence similarity to humans. The ruminants and cat showed amino acid content changes for the highest number of proteins (≥3/15). The pig, rabbit, dog and rodents had the closest global pI values to humans, while the cat showed the highest protein number (9/15) with pI values far from humans. GRAVY values for the pig and dog were the closest to humans. Tear-soluble factor study revealed that the pig was the only species with high similarity for all proteins (>60 %). Amino acid content was similar for most species compared to humans, except mouse for IL-6 and rodents and pig for IL-8. The pI and GRAVY values varied across species, though the pig and sheep were the only ones with similar pI to humans for four out of five factors.</div></div><div><h3>Conclusion</h3><div>The pig exhibited the highest similarity to humans in tear protein analysis among non-primate mammals, suggesting that the porcine model may be the most translational for DED research.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 260-272"},"PeriodicalIF":5.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931377","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":"Use of a transgenic mouse model for in vivo monitoring of corneal pathologies following Sulfur Mustard Exposure","authors":"Ariel Gore, Rahav Efrati, Shelly Atanelov, Pnina Glick, Maayan Cohen, Hila Gutman, Relli Gez, Vered Horwitz","doi":"10.1016/j.jtos.2025.04.007","DOIUrl":"10.1016/j.jtos.2025.04.007","url":null,"abstract":"<div><h3>Purpose</h3><div>The dynamic course of sulfur mustard (SM)-induced ocular insult involves an acute phase, which may progress to a chronic phase or a quiescent period, followed by late pathology. Visualizing pathological corneal changes in vivo could enhance understanding of this process and aid treatment development.</div></div><div><h3>Methods</h3><div>SM burn was induced in the right eyes of three transgenic mouse strains—expressing RFP under the VE-Cadherin promoter (blood vessels and hematopoietic cells), GFP under the keratin 15 promoter (limbal stem cells), and YFP under the Thy-1 promoter (mid-stromal nerve fibers, MSNFs)—by vapor exposure. Cell infiltration, neovascularization (NV), innervation loss, and stem cell (SC) depletion were monitored in vivo by stereomicroscopy for up to 8 weeks. Corneal whole-mounts were used to assess 360° structures, infiltrating cells, and subbasal nerve plexus (SNP) loss. Histology included H&E, Masson-Trichrome, and periodic acid-Schiff staining.</div></div><div><h3>Results</h3><div>A 35-s exposure caused minor ocular insult with moderate SNP changes, corneal cell infiltration, and reversible SC loss, mostly resolving by 4 weeks. A 120-s exposure caused severe insult with NV, extensive MSNF and SNP loss, marked CD45<sup>+</sup> and Iba1<sup>+</sup> infiltration, and irreversible SC depletion. NV, stromal inflammation, edema, epithelial changes, and goblet cells were seen in histology and correlated with fluorescence imaging.</div></div><div><h3>Conclusions</h3><div>This study demonstrates the utility of transgenic mice as powerful models for studying SM-induced ocular injury and for developing novel therapeutic strategies.</div></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"37 ","pages":"Pages 247-259"},"PeriodicalIF":5.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886679","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}