Pub Date : 2024-06-29DOI: 10.1016/j.jtos.2024.06.006
{"title":"Scrambler therapy as a novel treatment for unilateral ocular neuropathic pain","authors":"","doi":"10.1016/j.jtos.2024.06.006","DOIUrl":"10.1016/j.jtos.2024.06.006","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478302","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 : 2024-06-28DOI: 10.1016/j.jtos.2024.06.005
Duliurui Huang , Xinwei Jiao , Shenzhen Huang , Jiangman Liu , Hongli Si , Di Qi , Xiaoting Pei , Dingli Lu , Yimian Wang , Zhijie Li
Purpose
The lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting an aqueous layer of the tear film. However, a healthy lacrimal gland's inventory of cell types and heterogeneity remains understudied.
Methods
Here, 10X Genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 43,850 high-quality cells, we produced an atlas of cell heterogeneity and defined cell types using classic marker genes. The possible functions of these cells were analyzed through bioinformatics analysis. Additionally, the CellChat was employed for a preliminary analysis of the cell-cell communication network in the ELG.
Results
Over 37 subclasses of cells were identified, including seven types of glandular epithelial cells, three types of fibroblasts, ten types of myeloid-derived immune cells, at least eleven types of lymphoid-derived immune cells, and five types of vascular-associated cell subsets. The cell-cell communication network analysis revealed that fibroblasts and immune cells play a pivotal role in the dense intercellular communication network within the mouse ELG.
Conclusions
This study provides a comprehensive transcriptome atlas and related database of the mouse ELG.
{"title":"Analysis of the heterogeneity and complexity of murine extraorbital lacrimal gland via single-cell RNA sequencing","authors":"Duliurui Huang , Xinwei Jiao , Shenzhen Huang , Jiangman Liu , Hongli Si , Di Qi , Xiaoting Pei , Dingli Lu , Yimian Wang , Zhijie Li","doi":"10.1016/j.jtos.2024.06.005","DOIUrl":"10.1016/j.jtos.2024.06.005","url":null,"abstract":"<div><h3>Purpose</h3><p>The lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting an aqueous layer of the tear film. However, a healthy lacrimal gland's inventory of cell types and heterogeneity remains understudied.</p></div><div><h3>Methods</h3><p>Here<strong><em>,</em></strong> 10X Genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 43,850 high-quality cells, we produced an atlas of cell heterogeneity and defined cell types using classic marker genes. The possible functions of these cells were analyzed through bioinformatics analysis. Additionally, the CellChat was employed for a preliminary analysis of the cell-cell communication network in the ELG.</p></div><div><h3>Results</h3><p>Over 37 subclasses of cells were identified, including seven types of glandular epithelial cells, three types of fibroblasts, ten types of myeloid-derived immune cells, at least eleven types of lymphoid-derived immune cells, and five types of vascular-associated cell subsets. The cell-cell communication network analysis revealed that fibroblasts and immune cells play a pivotal role in the dense intercellular communication network within the mouse ELG.</p></div><div><h3>Conclusions</h3><p>This study provides a comprehensive transcriptome atlas and related database of the mouse ELG.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474250","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 : 2024-06-28DOI: 10.1016/j.jtos.2024.06.004
Maija Kauppila , Meri Vattulainen , Teemu O. Ihalainen , Anni Mörö , Tanja Ilmarinen , Heli Skottman
Purpose
Human donor corneas are an essential control tissue for corneal research. We utilized whole mount immunofluorescence (WM-IF) to evaluate how the storage affects the tissue integrity and putative limbal stem cells in human and porcine corneas. Moreover, we compare this information with the marker expression patterns observed in human pluripotent stem cell (hPSC)-derived LSCs.
Methods
The expression of putative LSC markers was analyzed with WM-IF and the fluorescence intensity was quantified in human donor corneas stored for 1–30 days, and in porcine corneas processed 0–6 h after euthanasia. The results were compared with the staining of human and porcine corneal cryosections and with both primary and hPSC-derived LSC cultures.
Results
WM-IF analyses emerged as a more effective method when compared to tissue sections for visualizing the expression of LSC markers within human and porcine corneas. Storage duration was a significant factor influencing the expression of LSC markers, as human tissues stored longer exhibited notable epithelial degeneration and lack of LSC markers. Porcine corneas replicated the expression patterns observed in fresh human tissue. We validated the diverse expression patterns of PAX6 in the limbal-corneal region, which aligned with findings from hPSC-LSC differentiation experiments.
Conclusions
WM-IF coupled with quantification of fluorescence intensities proved to be a valuable tool for investigating LSC marker expression in both human and porcine tissues ex vivo. Prolonged storage significantly influences the expression of LSC markers, underscoring the importance of fresh human or substitute control tissue when studying limbal stem cell biology.
{"title":"Whole mount immunofluorescence analysis of fresh and stored human donor corneas highlights changes in limbal characteristics during storage","authors":"Maija Kauppila , Meri Vattulainen , Teemu O. Ihalainen , Anni Mörö , Tanja Ilmarinen , Heli Skottman","doi":"10.1016/j.jtos.2024.06.004","DOIUrl":"10.1016/j.jtos.2024.06.004","url":null,"abstract":"<div><h3>Purpose</h3><p>Human donor corneas are an essential control tissue for corneal research. We utilized whole mount immunofluorescence (WM-IF) to evaluate how the storage affects the tissue integrity and putative limbal stem cells in human and porcine corneas. Moreover, we compare this information with the marker expression patterns observed in human pluripotent stem cell (hPSC)-derived LSCs.</p></div><div><h3>Methods</h3><p>The expression of putative LSC markers was analyzed with WM-IF and the fluorescence intensity was quantified in human donor corneas stored for 1–30 days, and in porcine corneas processed 0–6 h after euthanasia. The results were compared with the staining of human and porcine corneal cryosections and with both primary and hPSC-derived LSC cultures.</p></div><div><h3>Results</h3><p>WM-IF analyses emerged as a more effective method when compared to tissue sections for visualizing the expression of LSC markers within human and porcine corneas. Storage duration was a significant factor influencing the expression of LSC markers, as human tissues stored longer exhibited notable epithelial degeneration and lack of LSC markers. Porcine corneas replicated the expression patterns observed in fresh human tissue. We validated the diverse expression patterns of PAX6 in the limbal-corneal region, which aligned with findings from hPSC-LSC differentiation experiments.</p></div><div><h3>Conclusions</h3><p>WM-IF coupled with quantification of fluorescence intensities proved to be a valuable tool for investigating LSC marker expression in both human and porcine tissues <em>ex vivo</em>. Prolonged storage significantly influences the expression of LSC markers, underscoring the importance of fresh human or substitute control tissue when studying limbal stem cell biology.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000673/pdfft?md5=45543dc75923d02bb52b4130bb59b572&pid=1-s2.0-S1542012424000673-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-18DOI: 10.1016/j.jtos.2024.06.003
Sitong Shen , Yan Zhang
Corneal neovascularization (CoNV) is the second leading common cause of vision impairment worldwide and is a blinding pathological alteration brought on by ocular trauma, infection, and other factors. There are some limitations in the treatment of CoNV, hence it's critical to look into novel therapeutic targets. The corneal epithelial barrier, which is the initial barrier of the ocular surface, is an important structure that shields the eye from changes in the internal environment or invasion by the external environment. This study sought to collate evidence on the regulation of corneal epithelial barrier injury on the activation of vascular endothelial cells (VECs), basement membrane (BM) degradation, differentiation, migration, and proliferation of VECs, vascular maturation and stability, and other key processes in CoNV, so as to provide a novel concept for CoNV therapy targeting corneal epithelial barrier repair.
{"title":"Restoration of corneal epithelial barrier function: A possible target for corneal neovascularization","authors":"Sitong Shen , Yan Zhang","doi":"10.1016/j.jtos.2024.06.003","DOIUrl":"10.1016/j.jtos.2024.06.003","url":null,"abstract":"<div><p>Corneal neovascularization (CoNV) is the second leading common cause of vision impairment worldwide and is a blinding pathological alteration brought on by ocular trauma, infection, and other factors. There are some limitations in the treatment of CoNV, hence it's critical to look into novel therapeutic targets. The corneal epithelial barrier, which is the initial barrier of the ocular surface, is an important structure that shields the eye from changes in the internal environment or invasion by the external environment. This study sought to collate evidence on the regulation of corneal epithelial barrier injury on the activation of vascular endothelial cells (VECs), basement membrane (BM) degradation, differentiation, migration, and proliferation of VECs, vascular maturation and stability, and other key processes in CoNV, so as to provide a novel concept for CoNV therapy targeting corneal epithelial barrier repair.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433742","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 : 2024-06-11DOI: 10.1016/j.jtos.2024.06.002
Neel D. Pasricha , Ethan S. Lindgren , Rongshan Yan , Yien-Ming Kuo , Matilda Chan , Alan S. Verkman , Tifany Chu , Pattareeya Yottasan , Livia de Souza Goncalves , Onur Cil
Purpose
Ocular surface hydration is critical for eye health and its impairment can lead to dry eye disease. Extracellular calcium-sensing receptor (CaSR) is regulator of ion transport in epithelial cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. CFTR is also a major ion channel in ocular surface epithelia, however the roles of CaSR in ocular surface are not well studied. This study aims to investigate expression and functional roles of CaSR in ocular surface.
Methods
CaSR immunostaining was performed in mouse and human cornea and conjunctiva. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied cinacalcet (CaSR activator) and NPS-2143 (CaSR inhibitor).
Results
CaSR is expressed in corneal and conjunctival epithelia of mice and humans. Topically administered CaSR activator cinacalcet inhibits cAMP agonist forskolin-induced Cl− secretion and CFTR activity up to 90 %. CaSR inhibitor NPS-2143 stimulates CFTR-mediated Cl− secretion in mouse ocular surface, after which cAMP agonist forskolin had minimal additional secretory effects. Single dose NPS-2143 treatment (as an eye drop) increases tear fluid volume in mice by ∼60 % compared to vehicle treatment. NPS-2143 effect on tear volume lasts at least 8 h after single dose.
Conclusions
CaSR is a key regulator of ocular surface ion transport and CaSR inhibition promotes Cl− and tear secretion in the ocular surface. If they are found to be effective in in dry eye models, CaSR inhibitors (currently in clinical development) can potentially be repurposed as novel prosecretory treatments for dry eye disease.
{"title":"Calcium-sensing receptor (CaSR) modulates ocular surface chloride transport and its inhibition promotes ocular surface hydration","authors":"Neel D. Pasricha , Ethan S. Lindgren , Rongshan Yan , Yien-Ming Kuo , Matilda Chan , Alan S. Verkman , Tifany Chu , Pattareeya Yottasan , Livia de Souza Goncalves , Onur Cil","doi":"10.1016/j.jtos.2024.06.002","DOIUrl":"10.1016/j.jtos.2024.06.002","url":null,"abstract":"<div><h3>Purpose</h3><p>Ocular surface hydration is critical for eye health and its impairment can lead to dry eye disease. Extracellular calcium-sensing receptor (CaSR) is regulator of ion transport in epithelial cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) Cl<sup>−</sup> channel. CFTR is also a major ion channel in ocular surface epithelia, however the roles of CaSR in ocular surface are not well studied. This study aims to investigate expression and functional roles of CaSR in ocular surface.</p></div><div><h3>Methods</h3><p>CaSR immunostaining was performed in mouse and human cornea and conjunctiva. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied cinacalcet (CaSR activator) and NPS-2143 (CaSR inhibitor).</p></div><div><h3>Results</h3><p>CaSR is expressed in corneal and conjunctival epithelia of mice and humans. Topically administered CaSR activator cinacalcet inhibits cAMP agonist forskolin-induced Cl<sup>−</sup> secretion and CFTR activity up to 90 %. CaSR inhibitor NPS-2143 stimulates CFTR-mediated Cl<sup>−</sup> secretion in mouse ocular surface, after which cAMP agonist forskolin had minimal additional secretory effects. Single dose NPS-2143 treatment (as an eye drop) increases tear fluid volume in mice by ∼60 % compared to vehicle treatment. NPS-2143 effect on tear volume lasts at least 8 h after single dose.</p></div><div><h3>Conclusions</h3><p>CaSR is a key regulator of ocular surface ion transport and CaSR inhibition promotes Cl<sup>−</sup> and tear secretion in the ocular surface. If they are found to be effective in in dry eye models, CaSR inhibitors (currently in clinical development) can potentially be repurposed as novel prosecretory treatments for dry eye disease.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319443","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 : 2024-06-08DOI: 10.1016/j.jtos.2024.06.001
Aravind Roy , Smruti Rekha Priyadarshini , Sujata Das
Filamentary keratitis (FK) is a clinical sign of underlying ocular and systemic conditions. FK can cause significant irritation, tearing, and photophobia in the eye. It is a refractory debilitating condition caused by dry eye that affects the day-to-day activities of patients. The etiopathogenesis of FK is not well known; there are numerous predisposing causes. The condition starts as a sub-epithelial or Bowman's membrane dysfunction and leads to the shedding of epithelial cells that take a strand-like form and attach to the cornea. These strands are surrounded by mucin and continue to elongate to become filaments. The filament formation is further aided by the shearing action caused by eyelid movements. Several management approaches, such as addressing the underlying causes of filamentary keratitis, administering copious lubricants, topical corticosteroids, mucolytic agents, bandage contact lenses, punctal plugs, and mechanical removal of filaments are available. The prognosis is fair, and most cases resolve with occasional recurrences. Traditionally FK has been treated with lubricants, mechanical removal, and bandage contact lenses. The newer treatments are topical immunomodulators especially that treat filamentary keratitis associated with aqueous deficient dry eye. The review describes the treatment as well as pathogenesis.
丝状角膜炎(FK)是眼部和全身潜在疾病的一种临床表现。丝状角膜炎会对眼睛造成严重刺激、流泪和畏光。这是一种由干眼症引起的难治性衰弱症状,影响患者的日常活动。干眼症的发病机制尚不清楚,有许多诱发原因。干眼症的起因是上皮下或鲍曼膜功能障碍,导致上皮细胞脱落,呈股状附着在角膜上。这些股被粘蛋白包围,并继续伸长成为细丝。眼睑运动造成的剪切作用进一步促进了细丝的形成。有几种治疗方法可供选择,如解决丝状角膜炎的根本原因,使用大量润滑剂、外用皮质类固醇、粘液溶解剂、绷带式隐形眼镜、穿刺栓,以及用机械方法去除丝状物。预后尚可,大多数病例可治愈,偶尔复发。传统的 FK 治疗方法是使用润滑剂、机械清除法和绷带隐形眼镜。较新的治疗方法是局部使用免疫调节剂,尤其是治疗与缺水性干眼症相关的丝状角膜炎。这篇综述介绍了治疗方法和发病机理。
{"title":"Filamentary keratitis: A review","authors":"Aravind Roy , Smruti Rekha Priyadarshini , Sujata Das","doi":"10.1016/j.jtos.2024.06.001","DOIUrl":"10.1016/j.jtos.2024.06.001","url":null,"abstract":"<div><p>Filamentary keratitis (FK) is a clinical sign of underlying ocular and systemic conditions. FK can cause significant irritation, tearing, and photophobia in the eye. It is a refractory debilitating condition caused by dry eye that affects the day-to-day activities of patients. The etiopathogenesis of FK is not well known; there are numerous predisposing causes. The condition starts as a sub-epithelial or Bowman's membrane dysfunction and leads to the shedding of epithelial cells that take a strand-like form and attach to the cornea. These strands are surrounded by mucin and continue to elongate to become filaments. The filament formation is further aided by the shearing action caused by eyelid movements. Several management approaches, such as addressing the underlying causes of filamentary keratitis, administering copious lubricants, topical corticosteroids, mucolytic agents, bandage contact lenses, punctal plugs, and mechanical removal of filaments are available. The prognosis is fair, and most cases resolve with occasional recurrences. Traditionally FK has been treated with lubricants, mechanical removal, and bandage contact lenses. The newer treatments are topical immunomodulators especially that treat filamentary keratitis associated with aqueous deficient dry eye. The review describes the treatment as well as pathogenesis.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302360","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 : 2024-05-31DOI: 10.1016/j.jtos.2024.05.003
Fernando Martinez Guasch, Seema Sajjan, Ellis Tibbs, Cassidy Reandeau, Long Wu, Jerry Bohlen, Andrew Li, Amy Plotkin, Xuefang Cao, Sarah B. Sunshine
{"title":"A novel severity scoring system for murine ocular graft versus host disease and its correlation with CD3+ T cells in the cornea","authors":"Fernando Martinez Guasch, Seema Sajjan, Ellis Tibbs, Cassidy Reandeau, Long Wu, Jerry Bohlen, Andrew Li, Amy Plotkin, Xuefang Cao, Sarah B. Sunshine","doi":"10.1016/j.jtos.2024.05.003","DOIUrl":"10.1016/j.jtos.2024.05.003","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187195","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 : 2024-05-29DOI: 10.1016/j.jtos.2024.05.002
Yinglin Liao , Wenxin Zhao , Jing Yang , Jing Li , Juejing Chen , Ziyan Chen , Ling Jin , Longyue Li , Fen Huang , Lingyi Liang
Purpose
To investigate the delayed diagnosis of chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT), and further analyze potential confounding factors.
Methods
This cross-sectional study included 118 patients newly diagnosed as coGVHD after alloHCT at Zhongshan Ophthalmic Center, Sun Yat-sen University. All participants finished the flow path of medical history taking, detailed ophthalmological examination and questionnaire-based survey. coGVHD was diagnosed and graded by International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Lag time of diagnosis was defined as interval between noting of ocular symptoms and confirmed diagnosis of coGVHD (TN-D). We further compared the clinical parameters between groups categorized by the median TN-D as medium and long delay groups.
Results
The median TN-D was 6.3 [IQR 2.8–14.5] months. Most coGVHD patients underwent delayed diagnosis of coGVHD longer than 3 months (70 %, 83 of 118), with 90 of 118 diagnosed as severe coGVHD (76 %). The long delay group exhibited higher ICOGCG scores (10 [IQR 9–10.5] vs. 9 [IQR 8–10], P = 0.039) and more pronounced ocular signs, including conjunctival injection, meibomian gland loss, fibrotic tarsal conjunctiva, symblepharon, and corneal complications (all P < 0.05). Delayed diagnosis was strikingly correlated with seeking ophthalmic medical care twice or more prior to diagnosis (adjusted OR = 5.42, 95%CI: 1.40–21.06, P = 0.015) and accurate knowledge of ocular discomfort symptoms in coGVHD (adjusted OR = 0.29, 95%CI: 0.08–1.00, P = 0.050).
Conclusions
Delayed diagnosis of coGVHD, associated with disease severity, was common among alloHCT recipients in southern China. Improving patient education and the awareness of ophthalmologists may facilitate early diagnosis of coGVHD.
{"title":"Delayed diagnosis of ocular graft-versus-host disease after allogeneic hematopoietic stem cell transplantation","authors":"Yinglin Liao , Wenxin Zhao , Jing Yang , Jing Li , Juejing Chen , Ziyan Chen , Ling Jin , Longyue Li , Fen Huang , Lingyi Liang","doi":"10.1016/j.jtos.2024.05.002","DOIUrl":"10.1016/j.jtos.2024.05.002","url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the delayed diagnosis of chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT), and further analyze potential confounding factors.</p></div><div><h3>Methods</h3><p>This cross-sectional study included 118 patients newly diagnosed as coGVHD after alloHCT at Zhongshan Ophthalmic Center, Sun Yat-sen University. All participants finished the flow path of medical history taking, detailed ophthalmological examination and questionnaire-based survey. coGVHD was diagnosed and graded by International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Lag time of diagnosis was defined as interval between noting of ocular symptoms and confirmed diagnosis of coGVHD (T<sub>N-D</sub>). We further compared the clinical parameters between groups categorized by the median T<sub>N-D</sub> as medium and long delay groups.</p></div><div><h3>Results</h3><p>The median T<sub>N-D</sub> was 6.3 [IQR 2.8–14.5] months. Most coGVHD patients underwent delayed diagnosis of coGVHD longer than 3 months (70 %, 83 of 118), with 90 of 118 diagnosed as severe coGVHD (76 %). The long delay group exhibited higher ICOGCG scores (10 [IQR 9–10.5] vs. 9 [IQR 8–10], P = 0.039) and more pronounced ocular signs, including conjunctival injection, meibomian gland loss, fibrotic tarsal conjunctiva, symblepharon, and corneal complications (all P < 0.05). Delayed diagnosis was strikingly correlated with seeking ophthalmic medical care twice or more prior to diagnosis (adjusted OR = 5.42, 95%CI: 1.40–21.06, P = 0.015) and accurate knowledge of ocular discomfort symptoms in coGVHD (adjusted OR = 0.29, 95%CI: 0.08–1.00, P = 0.050).</p></div><div><h3>Conclusions</h3><p>Delayed diagnosis of coGVHD, associated with disease severity, was common among alloHCT recipients in southern China. Improving patient education and the awareness of ophthalmologists may facilitate early diagnosis of coGVHD.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185083","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 : 2024-05-04DOI: 10.1016/j.jtos.2024.04.008
Brandon Ebright , Zhiyuan Yu , Priyal Dave , Dante Dikeman , Sarah Hamm-Alvarez , Cintia S. de Paiva , Stan Louie
Purpose
Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution.
Methods
Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids.
Results
Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) were statistically significant. Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs.
Conclusion
In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. A consistent reduction was observed across all detected lipid analytes except for ꞷ-3 docosapentaenoic acid (DPA) and its special pro-resolving mediator (SPM) metabolites in aged mice, suggesting an increased risk for LG inflammation.
目的:多不饱和脂肪酸(PUFA)是调节炎症及其缓解的生物活性脂质的来源:方法:使用靶向脂质组学分析方法比较了年轻和年老 C57BL/6J 小鼠泪腺(LGs)中多不饱和脂肪酸代谢的变化,以及参与这些脂质代谢的酶的基因表达:结果:与年轻对照组相比,老年 LG 中的 PUFAs 及其代谢物全面减少,所有分析物的平均减少率在 25-66% 之间。ꞷ-6花生四烯酸(AA)代谢物在老年 LG 中全部减少,其中前列腺素 E2(PGE2)和脂氧素 A4(LXA4)的变化具有统计学意义。其他几种由 5-脂氧合酶(5-LOX)介导的代谢物在老年 LG 中也明显减少,包括 D 系列 resolvins(如 RvD4、RvD5 和 RvD6)。除了 RvDs 之外,一些ꞷ-3 二十二碳六烯酸(DHA)代谢物,如 14-HDHA、神经保护素 D1(NPD1)、Maresin 2(MaR2)和 MaR1 代谢物(22-COOH-MaR1)也在老化 LG 中明显减少。同样,ꞷ-3二十碳五烯酸(EPA)及其代谢物在老年 LG 中也明显减少,其中减少最明显的是 18-HEPE。利用特定代谢转换的代谢物比率(产物:前体)作为替代酶测量指标,可以确定老化 LG 中 12-LOX 活性降低:在这项研究中,与年轻对照组相比,发现老年雌性 C57BL/6J LG 中的 PUFAs 及其代谢物全面减少。除了ꞷ-3二十二碳五烯酸(DPA)及其特殊的促溶解介质(SPM)外,所有检测到的脂质分析物在老年小鼠中都出现了一致的减少,这表明LG炎症的风险增加了。
{"title":"Effects of age on lacrimal gland bioactive lipids","authors":"Brandon Ebright , Zhiyuan Yu , Priyal Dave , Dante Dikeman , Sarah Hamm-Alvarez , Cintia S. de Paiva , Stan Louie","doi":"10.1016/j.jtos.2024.04.008","DOIUrl":"10.1016/j.jtos.2024.04.008","url":null,"abstract":"<div><h3>Purpose</h3><p>Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution.</p></div><div><h3>Methods</h3><p>Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids.</p></div><div><h3>Results</h3><p>Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) were statistically significant. Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs.</p></div><div><h3>Conclusion</h3><p>In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. A consistent reduction was observed across all detected lipid analytes except for ꞷ-3 docosapentaenoic acid (DPA) and its special pro-resolving mediator (SPM) metabolites in aged mice, suggesting an increased risk for LG inflammation.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856410","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}