Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.08.009
Jennifer P. Craig , Monica Alves , James S. Wolffsohn , Laura E. Downie , Nathan Efron , Anat Galor , José Alvaro P. Gomes , Lyndon Jones , Maria Markoulli , Fiona Stapleton , Christopher E. Starr , Amy Gallant Sullivan , Mark D.P. Willcox , David A. Sullivan
The Tear Film & Ocular Surface Society (TFOS) Workshop entitled ‘A Lifestyle Epidemic: Ocular Surface Disease’ was a global initiative undertaken to establish the direct and indirect impacts of everyday lifestyle choices and challenges on ocular surface health. This article presents an executive summary of the evidence-based conclusions and recommendations of the 10-part TFOS Lifestyle Workshop report. Lifestyle factors described within the report include contact lenses, cosmetics, digital environment, elective medications and procedures, environmental conditions, lifestyle challenges, nutrition, and societal challenges. For each topic area, the current literature was summarized and appraised in a narrative-style review and the answer to a key topic-specific question was sought using systematic review methodology. The TFOS Lifestyle Workshop report was published in its entirety in the April 2023 and July 2023 issues of The Ocular Surface journal. Links to downloadable versions of the document and supplementary material, including report translations, are available on the TFOS website: http://www.TearFilm.org.
{"title":"TFOS Lifestyle Report Executive Summary: A Lifestyle Epidemic - Ocular Surface Disease","authors":"Jennifer P. Craig , Monica Alves , James S. Wolffsohn , Laura E. Downie , Nathan Efron , Anat Galor , José Alvaro P. Gomes , Lyndon Jones , Maria Markoulli , Fiona Stapleton , Christopher E. Starr , Amy Gallant Sullivan , Mark D.P. Willcox , David A. Sullivan","doi":"10.1016/j.jtos.2023.08.009","DOIUrl":"10.1016/j.jtos.2023.08.009","url":null,"abstract":"<div><p>The Tear Film & Ocular Surface Society (TFOS) Workshop entitled ‘A Lifestyle Epidemic: Ocular Surface Disease’ was a global initiative undertaken to establish the direct and indirect impacts of everyday lifestyle choices and challenges on ocular surface health. This article presents an executive summary of the evidence-based conclusions and recommendations of the 10-part <em>TFOS Lifestyle Workshop</em> report. Lifestyle factors described within the report include contact lenses, cosmetics, digital environment, elective medications and procedures, environmental conditions, lifestyle challenges, nutrition, and societal challenges. For each topic area, the current literature was summarized and appraised in a narrative-style review and the answer to a key topic-specific question was sought using systematic review methodology. The <em>TFOS Lifestyle Workshop</em> report was published in its entirety in the April 2023 and July 2023 issues of <em>The Ocular Surface</em> journal. Links to downloadable versions of the document and supplementary material, including report translations, are available on the TFOS website: <span>http://www.TearFilm.org</span><svg><path></path></svg>.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137973","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.09.008
Mohammad Soleimani , Reza Mirshahi , Kasra Cheraqpour , Seyed Mahbod Baharnoori , Hamed Massoumi , Collin Chow , Sumaiya Shahjahan , Bita Momenaei , Mohammad Javad Ashraf , Raghuram Koganti , Mahmood Ghassemi , Khandaker N. Anwar , Elmira Jalilian , Ali R. Djalilian
Purpose
Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model.
Methods
Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining.
Results
hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks).
Conclusions
Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.
{"title":"Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair","authors":"Mohammad Soleimani , Reza Mirshahi , Kasra Cheraqpour , Seyed Mahbod Baharnoori , Hamed Massoumi , Collin Chow , Sumaiya Shahjahan , Bita Momenaei , Mohammad Javad Ashraf , Raghuram Koganti , Mahmood Ghassemi , Khandaker N. Anwar , Elmira Jalilian , Ali R. Djalilian","doi":"10.1016/j.jtos.2023.09.008","DOIUrl":"10.1016/j.jtos.2023.09.008","url":null,"abstract":"<div><h3>Purpose</h3><p>Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries<span> have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model.</span></p></div><div><h3>Methods</h3><p><span>Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement<span>. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp<span> and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and </span></span></span>immunostaining.</p></div><div><h3>Results</h3><p><span>hBM-MSC injection successfully healed epithelial defects<span><span><span> regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced </span>corneal opacity and </span>neovascularization<span> and improved ASOCT parameters compared to subconjunctival injection or no treatment<span> (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by </span></span></span></span><em>in vivo</em> (up to 2 weeks) and <em>in vitro</em> assessments (up to 4 weeks).</p></div><div><h3>Conclusions</h3><p>Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144412","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.09.009
Damien Tuan-Man Le , Himal Kandel , Stephanie L. Watson
Aim
To identify and assess the quality of current validated questionnaires that could be used to evaluate ocular neuropathic pain and its associated aetiologies.
Methods
A literature search was performed on MEDLINE, PubMed, EMBASE, PsycINFO and The Cochrane Library. Articles evaluating questionnaires for ocular neuropathic pain and its associated aetiologies were included. Data on psychometric properties, validity, and reliability of the questionnaires was extracted and analysed using a set of quality criteria. Clinical and demographical associations with ocular neuropathic pain were also reviewed.
Results
The search generated 1738 results with 61 publications meeting the inclusion criteria. The 61 publications covered 28 questionnaires including 3 ocular pain, 12 dry eye disease, 2 blepharitis, 2 refractive surgery, 3 contact lens wear, 3 Sjogren's Syndrome, and 3 that were non-disease-specific. Only 57 publications provided enough data on psychometric properties and validity of the questionnaire to be included for quality assessment. The Contact Lens Discomfort Index (CLDI) had the highest rated psychometric properties, whereas the English version of the Ocular Comfort Index (OCI) provided the most data on psychometric properties (9 out of 10 criteria). Most ocular pain and disease-specific questionnaires contained appropriate items to assess ocular pain in specific populations. However, non-disease-specific ophthalmic questionnaires demonstrated poor reliability and validity when evaluating ocular pain.
Conclusion
Ocular pain questionnaires can potentially diagnose ocular neuropathic pain. Disease-specific questionnaires were limited to their target populations, and non-disease-specific ophthalmic questionnaires were unreliable. Further studies are required to determine the most appropriate questionnaire to evaluate ocular neuropathic pain.
{"title":"Evaluation of ocular neuropathic pain","authors":"Damien Tuan-Man Le , Himal Kandel , Stephanie L. Watson","doi":"10.1016/j.jtos.2023.09.009","DOIUrl":"10.1016/j.jtos.2023.09.009","url":null,"abstract":"<div><h3>Aim</h3><p>To identify and assess the quality of current validated questionnaires that could be used to evaluate ocular neuropathic pain and its associated aetiologies.</p></div><div><h3>Methods</h3><p>A literature search was performed on MEDLINE, PubMed, EMBASE, PsycINFO and The Cochrane Library. Articles evaluating questionnaires for ocular neuropathic pain and its associated aetiologies were included. Data on psychometric properties, validity, and reliability of the questionnaires was extracted and analysed using a set of quality criteria. Clinical and demographical associations with ocular neuropathic pain were also reviewed.</p></div><div><h3>Results</h3><p>The search generated 1738 results with 61 publications meeting the inclusion criteria. The 61 publications covered 28 questionnaires including 3 ocular pain, 12 dry eye disease, 2 blepharitis, 2 refractive surgery, 3 contact lens wear, 3 Sjogren's Syndrome, and 3 that were non-disease-specific. Only 57 publications provided enough data on psychometric properties and validity of the questionnaire to be included for quality assessment. The Contact Lens Discomfort Index (CLDI) had the highest rated psychometric properties, whereas the English version of the Ocular Comfort Index (OCI) provided the most data on psychometric properties (9 out of 10 criteria). Most ocular pain and disease-specific questionnaires contained appropriate items to assess ocular pain in specific populations. However, non-disease-specific ophthalmic questionnaires demonstrated poor reliability and validity when evaluating ocular pain.</p></div><div><h3>Conclusion</h3><p>Ocular pain questionnaires can potentially diagnose ocular neuropathic pain. Disease-specific questionnaires were limited to their target populations, and non-disease-specific ophthalmic questionnaires were unreliable. Further studies are required to determine the most appropriate questionnaire to evaluate ocular neuropathic pain.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160178","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.08.007
Guoliang Wang , Lina Xu , Ruize Shi , Yingyue Ye , Baihui Zeng , Xiuqin Yang , Zeyu Liu , Zhen Liu , Shurong Wang , Yuhua Xue , Cheng Li
Purpose
Meibomian glands (MGs) are crucial for maintaining tear film stability and ocular surface health. Here, we aim to establish a novel organotypic culture model of MGs and explore the risk factors of MG dysfunction (MGD).
Methods
We developed a novel organotypic culture model for MGs at the air-liquid interface. The viability and cell proliferation of MGs were assessed using CCK-8, immunofluorescence, and qPCR. Lipid accumulation was evaluated by Nile red staining and microscopic examination. Protein expression levels were evaluated by immunofluorescence and Western blot assay. EdU assay was employed to track the proliferation of acinar cells. The validity of the model was confirmed through culturing MGs from mice of different ages and incorporating certain drugs (Dex) into the culture system.
Results
Utilizing the novel culture model, the MG tissue exhibited sustained viability, cellular division, and continuous production of lipids for a duration of 7 days. Lipid droplets formed were directly visualized using light field microscopy. Through the cultivation of aged mice's MGs, it was discovered that aging resulted in diminished proliferation and lipid synthesis, along with an aberrant increase in Krt10 expression. Further application of this model showed that Dex treatment diminished MG's proliferation and lipid synthesis. Finally, an in vivo study was conducted to provide additional confirmation of the phenomenon of Dex-induced abnormalities.
Conclusions
In this study, a stable organotypic culture model of the MGs was established. The organotypic culture model offers a valuable tool to investigate the pathophysiological mechanisms and facilitate drug screening for MG-related diseases.
{"title":"Organotypic culture model of mouse meibomian gland as a screening platform for risk factors related to meibomian gland dysfunction","authors":"Guoliang Wang , Lina Xu , Ruize Shi , Yingyue Ye , Baihui Zeng , Xiuqin Yang , Zeyu Liu , Zhen Liu , Shurong Wang , Yuhua Xue , Cheng Li","doi":"10.1016/j.jtos.2023.08.007","DOIUrl":"10.1016/j.jtos.2023.08.007","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Meibomian glands (MGs) are crucial for maintaining tear film stability and </span>ocular surface<span> health. Here, we aim to establish a novel organotypic culture model of MGs and explore the risk factors of MG dysfunction (MGD).</span></p></div><div><h3>Methods</h3><p><span><span><span>We developed a novel organotypic culture model for MGs at the air-liquid interface. The viability and cell proliferation of MGs were assessed using CCK-8, </span>immunofluorescence<span><span>, and qPCR. Lipid accumulation was evaluated by </span>Nile red<span> staining and microscopic examination. Protein expression levels were evaluated by immunofluorescence and </span></span></span>Western blot assay. </span>EdU<span><span> assay was employed to track the proliferation of acinar cells. The validity of the model was confirmed through culturing MGs from mice of different ages and incorporating certain </span>drugs (Dex) into the culture system.</span></p></div><div><h3>Results</h3><p>Utilizing the novel culture model, the MG tissue exhibited sustained viability, cellular division, and continuous production of lipids for a duration of 7 days. Lipid droplets<span><span> formed were directly visualized using light field microscopy. Through the cultivation of aged mice's MGs, it was discovered that aging resulted in diminished proliferation and lipid synthesis<span>, along with an aberrant increase in Krt10 expression. Further application of this model showed that Dex </span></span>treatment diminished MG's proliferation and lipid synthesis. Finally, an in vivo study was conducted to provide additional confirmation of the phenomenon of Dex-induced abnormalities.</span></p></div><div><h3>Conclusions</h3><p>In this study, a stable organotypic culture model of the MGs was established. The organotypic culture model offers a valuable tool to investigate the pathophysiological mechanisms and facilitate drug screening for MG-related diseases.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101367","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.08.004
Yashaswini Kelagere , Kaitlin K. Scholand , Erica N. DeJong , Andrea I. Boyd , Zhiyuan Yu , Roger A. Astley , Michelle C. Callegan , Dawn ME. Bowdish , Helen P. Makarenkova , Cintia S. de Paiva
Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), IFN-γ, IL-12p40, IL-17, and IL-10 proteins in tears of aged mice. Moreover, genetic loss of the Tnf−/− in mice decreased goblet cell loss and the development of ectopic lymphoid structures in the lacrimal gland compared to wild-type mice. This was accompanied by a decrease in cytokine production. Treatment of mice at an early stage of aging (12-14-month-old) with TNF inhibitor tanfanercept eye drops for eight consecutive weeks decreased cytokine levels in tears, improved goblet cell density, and decreased the marginal zone B cell frequency in the lacrimal gland compared to vehicle-treated animals. Our studies indicate that modulation of TNF during aging could be a novel strategy for age-related dry eye disease.
{"title":"TNF is a critical cytokine in age-related dry eye disease","authors":"Yashaswini Kelagere , Kaitlin K. Scholand , Erica N. DeJong , Andrea I. Boyd , Zhiyuan Yu , Roger A. Astley , Michelle C. Callegan , Dawn ME. Bowdish , Helen P. Makarenkova , Cintia S. de Paiva","doi":"10.1016/j.jtos.2023.08.004","DOIUrl":"10.1016/j.jtos.2023.08.004","url":null,"abstract":"<div><p><span><span>Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and </span>lacrimal gland<span><span><span>. Tumor necrosis factor<span> (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as </span></span>cathepsin S<span><span>, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the </span>ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 </span></span>receptor alpha (CD25), IFN-γ, IL-12p40, IL-17, and IL-10 proteins in tears of aged mice. Moreover, genetic loss of the </span></span><em>Tnf</em><sup>−/−</sup><span><span> in mice decreased goblet cell loss and the development of ectopic lymphoid structures in the lacrimal gland compared to wild-type mice. This was accompanied by a decrease in </span>cytokine production<span>. Treatment<span> of mice at an early stage of aging (12-14-month-old) with TNF inhibitor tanfanercept eye drops for eight consecutive weeks decreased cytokine levels in tears, improved goblet cell density, and decreased the marginal zone B cell frequency in the lacrimal gland compared to vehicle-treated animals. Our studies indicate that modulation of TNF during aging could be a novel strategy for age-related dry eye disease.</span></span></span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229912","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.11.001
M. Desira, E. Gabison, P.V. Jacomet, D. Denis, F. Dalmas, T. David, A. Aziz
{"title":"A new treatment changes the game: An innovative management of a child suffering from severe ligneous conjunctivitis with type 1 plasminogen deficiency","authors":"M. Desira, E. Gabison, P.V. Jacomet, D. Denis, F. Dalmas, T. David, A. Aziz","doi":"10.1016/j.jtos.2023.11.001","DOIUrl":"10.1016/j.jtos.2023.11.001","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296882","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}
Part of the lacrimal functional unit, the cornea protects the ocular surface from numerous environmental aggressions and xenobiotics. Toxicological evaluation of compounds remains a challenge due to complex interactions between corneal nerve endings and epithelial cells. To this day, models do not integrate the physiological specificity of corneal nerve endings and are insufficient for the detection of low toxic effects essential to anticipate Toxicity-Induced Dry Eye (TIDE).
Using high-content imaging tool, we here characterize toxicity-induced cellular alterations using primary cultures of mouse trigeminal sensory neurons and corneal epithelial cells in a compartmentalized microfluidic chip.
We validate this model through the analysis of benzalkonium chloride (BAC) toxicity, a well-known preservative in eyedrops, after a single (6h) or repeated (twice a day for 15 min over 5 days) topical 5.10−4% BAC applications on the corneal epithelial cells and nerve terminals.
In combination with high-content image analysis, this advanced microfluidic protocol reveal specific and tiny changes in the epithelial cells and axonal network as well as in trigeminal cells, not directly exposed to BAC, with ATF3/6 stress markers and phospho-p44/42 cell activation marker. Altogether, this corneal neuroepithelial chip enables the evaluation of toxic effects of ocular xenobiotics, distinguishing the impact on corneal sensory innervation and epithelial cells. The combination of compartmentalized co-culture/high-content imaging/multiparameter analysis opens the way for the systematic analysis of toxicants but also neuroprotective compounds.
{"title":"Corneal neuroepithelial compartmentalized microfluidic chip model for evaluation of toxicity-induced dry eye","authors":"Noémie Bonneau , Anaïs Potey , Michael-Adrien Vitoux , Romain Magny , Camille Guerin , Christophe Baudouin , Jean-Michel Peyrin , Françoise Brignole-Baudouin , Annabelle Réaux-Le Goazigo","doi":"10.1016/j.jtos.2023.11.004","DOIUrl":"10.1016/j.jtos.2023.11.004","url":null,"abstract":"<div><p><span>Part of the lacrimal functional unit, the cornea protects the ocular surface from numerous environmental aggressions and </span>xenobiotics<span>. Toxicological evaluation of compounds remains a challenge due to complex interactions between corneal nerve endings and epithelial cells. To this day, models do not integrate the physiological specificity of corneal nerve endings and are insufficient for the detection of low toxic effects essential to anticipate Toxicity-Induced Dry Eye (TIDE).</span></p><p>Using high-content imaging tool, we here characterize toxicity-induced cellular alterations using primary cultures of mouse trigeminal sensory neurons and corneal epithelial cells in a compartmentalized microfluidic chip.</p><p>We validate this model through the analysis of benzalkonium chloride (BAC) toxicity, a well-known preservative in eyedrops, after a single (6h) or repeated (twice a day for 15 min over 5 days) topical 5.10<sup>−4</sup>% BAC applications on the corneal epithelial cells and nerve terminals.</p><p><span>In combination with high-content image analysis, this advanced microfluidic protocol reveal specific and tiny changes in the epithelial cells and axonal network as well as in trigeminal cells, not directly exposed to BAC, with ATF3/6 stress markers and phospho-p44/42 cell activation marker. Altogether, this corneal neuroepithelial chip enables the evaluation of toxic effects of ocular xenobiotics, distinguishing the impact on corneal sensory innervation and epithelial cells. The combination of compartmentalized co-culture/high-content imaging/multiparameter analysis opens the way for the systematic analysis of toxicants but also </span>neuroprotective compounds.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138178392","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.09.012
Menglu Yang , Vanessa Delcroix , Anton Lennikov , Nicholas Wang , Helen P. Makarenkova , Darlene A. Dartt
Purpose
Primary Sjögren's syndrome (pSS) is an autoimmune disease that mainly attacks the lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates the DNA sensing mechanism in the pathogenesis of pSS. The purpose of the present study is to determine the pro-inflammatory effect of self-genomic DNA (gDNA) on myoepithelial cells (MECs), which along with acinar and ductal cells is a major cell type of the lacrimal gland.
Method
MECs primary culture was acquired from female C57BL6J mice. Genomic DNA was extracted from the spleen of the same animal. The MECs were challenged with self-gDNA. The cytokine secretion was detected using supernatant by enzyme-linked immunosorbent assay (ELISA). The activation of inflammasomes was determined using FAM-FLICA. Cryosections of NOD.B10.H2b mouse model of pSS were obtained for immunofluorescence microscopy (IF), with Balb/C as control.
Result
Treatment with gDNA activated AIM2 inflammasome assembly and function, leading to secretion of interleukin (IL)-1β and IL-18 in MECs. The stimulation of IL-1β secretion by gDNA appeared to be solely at the post-translational level, whereas IL-18 secretion was a combination of increased protein synthesis and post-translational modification. Genomic DNA also induced the activation of STimulators of INterferon Genes (STING), which correlated to the activation of STING in the lacrimal gland from the NOD.B10.H2b mouse. STING activation led to the secretion of IFN-β via Nuclear Factor-κB (NF-κB). The IFN-β further enhances the secretion of IL-1β. The contractility of MECs was disabled by treatment with gDNA or poly AnT, independent of the level of intracellular [Ca2+].
Conclusion
Self-gDNA induces a proinflammatory response in lacrimal gland MECs by activating both the AIM2 inflammasome and STING and thus may contribute to the pathogenesis of pSS.
{"title":"Genomic DNA activates the AIM2 inflammasome and STING pathways to induce inflammation in lacrimal gland myoepithelial cells","authors":"Menglu Yang , Vanessa Delcroix , Anton Lennikov , Nicholas Wang , Helen P. Makarenkova , Darlene A. Dartt","doi":"10.1016/j.jtos.2023.09.012","DOIUrl":"10.1016/j.jtos.2023.09.012","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Primary Sjögren's syndrome (pSS) is an autoimmune disease that mainly attacks the </span>lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates the DNA sensing mechanism in the pathogenesis of pSS. The purpose of the present study is to determine the pro-inflammatory effect of self-genomic DNA (gDNA) on myoepithelial cells (MECs), which along with acinar and ductal cells is a major cell type of the lacrimal gland.</p></div><div><h3>Method</h3><p><span>MECs primary culture<span> was acquired from female C57BL6J mice. Genomic DNA was extracted from the spleen of the same animal. The MECs were challenged with self-gDNA. The cytokine secretion<span> was detected using supernatant by enzyme-linked immunosorbent assay (ELISA). The activation of inflammasomes was determined using FAM-FLICA. Cryosections of NOD.B10.H2</span></span></span><sup>b</sup><span> mouse model of pSS were obtained for immunofluorescence microscopy (IF), with Balb/C as control.</span></p></div><div><h3>Result</h3><p><span>Treatment<span><span> with gDNA activated AIM2<span> inflammasome assembly and function, leading to secretion of interleukin<span> (IL)-1β and IL-18 in MECs. The stimulation of IL-1β secretion by gDNA appeared to be solely at the post-translational level, whereas IL-18 secretion was a combination of increased protein synthesis and post-translational modification. Genomic DNA also induced the activation of STimulators of </span></span></span>INterferon Genes (STING), which correlated to the activation of STING in the lacrimal gland from the NOD.B10.H2</span></span><sup>b</sup><span> mouse. STING activation led to the secretion of IFN-β via Nuclear Factor-κB (NF-κB). The IFN-β further enhances the secretion of IL-1β. The contractility of MECs was disabled by treatment with gDNA or poly AnT, independent of the level of intracellular [Ca</span><sup>2+</sup>].</p></div><div><h3>Conclusion</h3><p>Self-gDNA induces a proinflammatory response in lacrimal gland MECs by activating both the AIM2 inflammasome and STING and thus may contribute to the pathogenesis of pSS.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173653","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.09.006
Philipp Steven , Victor L. Perez , Ajay Sharma
Graft versus host disease (GVHD) remains a major and serious complication of allogeneic hematopoietic stem cell transplantation. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD. Mouse models have played an important role in understanding the several key elements of GVHD pathobiology. The current review discusses the immunology, pathology, and key phenotypic features of mouse models of systemic GVHD. Furthermore, a critical appraisal of mouse models of ocular GVHD (oGVHD) is provided. The disease mechanisms underlying the ocular surface, meibomian gland, and lacrimal gland injury in these models are reviewed, and the relevance of oGVHD murine models to clinical oGVHD is also included.
{"title":"Murine models of graft versus host disease (GVHD): Focus on ocular GVHD","authors":"Philipp Steven , Victor L. Perez , Ajay Sharma","doi":"10.1016/j.jtos.2023.09.006","DOIUrl":"10.1016/j.jtos.2023.09.006","url":null,"abstract":"<div><p><span>Graft versus host disease (GVHD) remains a major and serious complication of </span>allogeneic hematopoietic stem cell transplantation<span><span>. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology<span>, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD. Mouse models have played an important role in understanding the several key elements of GVHD pathobiology. The current review discusses the immunology, pathology, and key phenotypic features of mouse models of systemic GVHD. Furthermore, a critical appraisal of mouse models of ocular GVHD (oGVHD) is provided. The disease mechanisms underlying the </span></span>ocular surface<span><span>, meibomian gland, and </span>lacrimal gland injury in these models are reviewed, and the relevance of oGVHD murine models to clinical oGVHD is also included.</span></span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171838","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}
Pub Date : 2023-10-01DOI: 10.1016/j.jtos.2023.11.003
Isabel Moreno , Sudhir Verma , Tarsis Ferreira Gesteira , Vivien J. Coulson- Thomas
Meibomian glands (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer inflammatory cell infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.
{"title":"Recent advances in age-related meibomian gland dysfunction (ARMGD)","authors":"Isabel Moreno , Sudhir Verma , Tarsis Ferreira Gesteira , Vivien J. Coulson- Thomas","doi":"10.1016/j.jtos.2023.11.003","DOIUrl":"10.1016/j.jtos.2023.11.003","url":null,"abstract":"<div><p><span><span>Meibomian glands<span> (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction<span> (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology<span> of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, </span></span></span></span>hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer </span>inflammatory cell<span> infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.</span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138049106","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}