{"title":"TGF-β1-mediated upregulation of LMCD1 drives corneal myofibroblast differentiation and corneal fibrosis","authors":"Yunlan Tang , Liyan Xu , Yiran Yang , Fangyuan Qin , Feiying Meng , Lijuan Dai , Zhihong Meng , Shengwei Ren","doi":"10.1016/j.exer.2024.110130","DOIUrl":"10.1016/j.exer.2024.110130","url":null,"abstract":"<div><div>Transforming growth factor β1 (TGF-β1) drives corneal fibroblasts to differentiate into corneal myofibroblasts and plays a key role in corneal fibrosis. However, the role of LIM and cysteine-rich domains-1 (LMCD1) in TGF-β1-induced corneal myofibroblast differentiation and corneal fibrosis remains elusive. Thus, this study aimed to investigate the expression, regulatory mechanism, and role of LMCD1 in TGF-β1-induced corneal myofibroblast differentiation and corneal fibrosis. The expression of LMCD1 in TGF-β1-stimulated corneal fibroblasts was found to be upregulated through mRNA sequencing, quantitative PCR (qPCR), and Western blotting. Moreover, LMCD1 was identified to be upregulated in a mouse model of corneal fibrosis via qPCR and Western blotting. Additionally, our results demonstrated that the increase in LMCD1 expression induced by TGF-β1 in corneal fibroblasts was primarily regulated by the SMAD3 signaling pathway. Furthermore, LMCD1 knockdown significantly inhibited TGF-β1-induced corneal fibroblast-to-myofibroblast differentiation and simultaneously activated SMAD3, JNK, and p38 by promoting <em>TGF-β1</em> transcription. These findings collectively suggest that LMCD1 could upregulate alpha-smooth muscle actin (α-SMA) expression and downregulate TGF-β1 expression in corneal myofibroblast differentiation. Consequently, upregulation of LMCD1 expression could potentially serve as a strategy to mediate the TGF-β1 signaling pathway in corneal myofibroblast differentiation and corneal fibrosis, laying a theoretical reference for corneal fibrosis and contributing to the development of effective therapeutic strategies for corneal fibrosis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110130"},"PeriodicalIF":3.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingjing Cai , Fei Liao , Yandie Mao , Shuyi Liu , Xiong Wu , Shiqi Tang , Simin Wang , Ge Shan , Shengzhou Wu
{"title":"Regulation of LAMTOR1 by oxidative stress in retinal pigment epithelium: Implications for age-related macular degeneration pathogenesis","authors":"Jingjing Cai , Fei Liao , Yandie Mao , Shuyi Liu , Xiong Wu , Shiqi Tang , Simin Wang , Ge Shan , Shengzhou Wu","doi":"10.1016/j.exer.2024.110129","DOIUrl":"10.1016/j.exer.2024.110129","url":null,"abstract":"<div><div>Oxidative stress is a critical pathogenic factor for age-related macular degeneration (AMD). Autophagy serves as a mechanism to counteract oxidative stress. LAMTOR1 regulates mTORC1 activity by recruiting or disassembling it on the lysosome under the addition or deprivation of amino acids. This regulation inhibits or enhances autophagy. Our study investigates whether oxidative stress impacts LAMTOR1, thereby adapting to oxidative conditions. We employed oxidative stressors, menadione (VK3) and 4-hydroxynonenal (4-HNE), and observed a reduction of LAMTOR1 in both human and mouse retinal pigment epithelium (RPE) following short-term (1h) and prolonged exposures (24h). Nrf2 overexpression increased both <em>lamtor1</em> mRNA and LAMTOR1 protein in the RPE. To determine if Nrf2 regulates <em>lamtor1</em> transcription, we cloned the deletion mutants of the <em>lamtor1</em> promoter into a luciferase reporter. Although the promoter contained antioxidant response elements, transcriptional activity depended on the interaction between Nrf2 and the constructs containing the transcriptional start site. Moreover, Nrf2-driven transcription was significantly reduced by an inhibitor of histone acetyltransferase, p300. Correspondingly, Nrf2 overexpression increased levels of acetylated histone 3 and p300. The reduction in LAMTOR1 by 4-HNE was reversed by pepstatin A and NH<sub>4</sub>Cl which block lysosomal degradation. 4-HNE increased TFEB nuclear translocation which was reversed by LAMTOR1 overexpression. <em>In vivo</em>, LAMTOR1 levels decreased in the photoreceptor and RPE layers of NaIO<sub>3</sub>-injected mice, compared to PBS-injected controls. In conclusion, oxidative injury reduces LAMTOR1, predominantly through lysosomal degradation although Nrf2-mediated histone acetylation enhances <em>lamtor1</em> transcription. This study reveals a previously unrecognized regulatory mechanism of <em>lamtor1</em> by oxidative stress, suggesting a novel role for LAMTOR1 in the pathogenesis of AMD.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110129"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuefei Ding , Zhaochuan Liu , Hailong Li , Peilin Yue , Yuxuan Jia , Enjie Li , Ningxin Lv , Ting Chen , Rui Fang , Honggang Zhou , Xudong Song
{"title":"Binding with HSP90β, cimifugin ameliorates fibrotic cataracts in vitro and in vivo by inhibiting TGFβ signaling pathways","authors":"Xuefei Ding , Zhaochuan Liu , Hailong Li , Peilin Yue , Yuxuan Jia , Enjie Li , Ningxin Lv , Ting Chen , Rui Fang , Honggang Zhou , Xudong Song","doi":"10.1016/j.exer.2024.110127","DOIUrl":"10.1016/j.exer.2024.110127","url":null,"abstract":"<div><div>Fibrotic cataracts, the most frequent complications after phacoemulsification, cannot be cured by drugs in clinic. The primary mechanism underlying the disease is the epithelial-mesenchymal transition (EMT). Cimifugin is a natural monomer component of traditional Chinese medicines. Previous researches have demonstrated the effect of cimifugin inhibiting EMT in the lung. The purpose of this work is to evaluate the impact of cimifugin on EMT in the lens and elucidate its precise mechanism. The pathogenesis of fibrotic cataracts was simulated using TGFβ2-induced cell model of EMT and the injury-induced anterior subcapsular cataract animal model. Through H&E staining and immunofluorescence of mice eyeballs, we discovered that cimifugin can inhibit the expansion of fibrotic lesions in vivo. Furthermore, at mRNA and protein levels, we confirmed that cimifugin can allay EMT of lens epithelial cells (LECs) in vitro and in vivo. Additionally, the inhibition of cimifugin on the activation of TGFβ-related signaling pathways was certified by immunoblot. HSP90β, the target of cimifugin, was predicted by network pharmacology and verified by drug affinity responsive target stability, the cellular thermal shift assay, and microscale thermophoresis. Moreover, co-immunoprecipitation revealed the interaction between HSP90β and TGFβ receptor (TGFβR) II. Together, our findings showed that by weakening the binding of HSP90β and TGFβRII, cimifugin suppressed the TGFβ signaling pathways to alleviate fibrotic cataracts. Cimifugin is a promising medication for the treatment of fibrotic cataracts.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110127"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert F. Mullins , Miles J. Flamme-Wiese , Emma M. Navratil , Erin A. Boese , Katayoun Varzavand , Megan J. Riker , Kai Wang , Edwin M. Stone , Budd A. Tucker
{"title":"Ghost vessels in the eye: Cell free choriocapillaris domains in atrophic age-related macular degeneration","authors":"Robert F. Mullins , Miles J. Flamme-Wiese , Emma M. Navratil , Erin A. Boese , Katayoun Varzavand , Megan J. Riker , Kai Wang , Edwin M. Stone , Budd A. Tucker","doi":"10.1016/j.exer.2024.110128","DOIUrl":"10.1016/j.exer.2024.110128","url":null,"abstract":"<div><div>The choriocapillaris is a dense vascular bed in the inner choroid that supplies the photoreceptor cells and retinal pigment epithelium (RPE). While loss of choriocapillaris density has been described in association with age-related macular degeneration (AMD), whether these changes are primary or secondary to RPE degenerative changes in AMD has been debated. In this study we characterized choriocapillaris loss by quantifying “ghost” vessels in a series of 99 human donor maculae labeled with the UEA-I lectin, and found significant increases in early-intermediate AMD and a greater difference in geographic atrophy in areas with intact RPE. Eyes were genotyped at the <em>CFH</em> Tyr402His locus, and those homozygous for the His allele showed significantly more ghost vessels than those with other genotypes. When only non-AMD eyes were evaluated, His homozygotes had increased ghost vessel density but this trend did not reach statistical significance. These results support the notion that choriocapillaris death often precedes RPE degeneration in AMD and that this loss is an important therapeutic consideration for AMD.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110128"},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nan Zhang , Dongxiao Ji , Yixin Hu , Pengyu Zhang , Xizhi Deng , Min Zhu , Wen Zeng , Min Ke
{"title":"The role of nicotinamide riboside in the preservation of retinal ganglion cells using an in vitro glutamate-induced excitotoxicity model","authors":"Nan Zhang , Dongxiao Ji , Yixin Hu , Pengyu Zhang , Xizhi Deng , Min Zhu , Wen Zeng , Min Ke","doi":"10.1016/j.exer.2024.110126","DOIUrl":"10.1016/j.exer.2024.110126","url":null,"abstract":"<div><div>Delaying or preventing the loss of retinal ganglion cells (RGCs) in glaucoma is needed for vision preservation. Glutamate-mediated neurotoxicity arises from the excessive stimulation of N-methyl-D-aspartate membrane receptors by glutamate. This overstimulation, occurring specifically in RGCs, triggers a progressive deterioration of the optic nerve that ultimately leads to the vision loss in glaucoma. Our previous investigation demonstrated that nicotinamide riboside (NR) effectively preserved RGCs in multiple mouse models of glaucoma. To investigate the precise role of NR concerning RGCs which remains uncertain, a glutamate-induced excitotoxicity RGCs damage model was established using R28 cells in this study. Results showed that NR treatment could not only prevent the decrease in cell viability but also effectively inhibit the apoptosis of R28 cells induced by glutamate, as proven by flow cytometry and expression of key pro-apoptotic proteins. Additionally, it significantly attenuated oxidative stress induced by glutamate, as evaluated by the production of inflammatory factors, reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Furthermore, NR elevated the intracellular nicotinamide adenine dinucleotide (NAD+) levels in R28 cells. Lastly, we used RNA-seq to reveal the underlying mechanism of NR protection. Combining the results of RNA-seq and Western blot, we found that NR also restored the decreased protein expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) induced by glutamate. These findings strongly indicated that NR exhibits a protective effect against R28 cell apoptosis in a glutamate-induced excitotoxicity RGCs damage model. This protective effect is likely mediated through the activation of the SIRT1/PGC1α pathway, achieved by increasing intracellular NAD + levels.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110126"},"PeriodicalIF":3.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Choroidal melanocyte secretome from cultured cells and tissue-engineered choroid models exposed to acute or chronic oxidative stress","authors":"Samira Karami , Solange Landreville , Stéphanie Proulx","doi":"10.1016/j.exer.2024.110125","DOIUrl":"10.1016/j.exer.2024.110125","url":null,"abstract":"<div><div>The choroid, located between the retina and the sclera, is a vascularized and pigmented connective tissue, playing a crucial role in providing oxygen and nutrients to the outer layers of the retina, and in absorbing excessive light. How choroidal melanocytes (CMs) participate in tissue homeostasis through paracrine signaling with neighboring cells is poorly understood. In this study, using two-dimensional and three-dimensional models, we aimed to identify proteins secreted by CMs under different oxidative stress conditions. To do so, CMs, choroidal fibroblasts (CFs), and retinal pigment epithelial (RPE) cells were isolated from native human RPE/choroidal tissues and expanded. RNA was isolated and processed for gene profiling analysis. The self-assembly approach of tissue engineering was used to form 3D stromal substitutes, and RPE cells and/or CMs were added to produce 3D models with different cell combinations. The medium conditioned by cells in 2D and 3D cultures was collected in a non-stressed condition and following acute or chronic oxidative stress exposures, then proteome and ELISA analyses were performed to identify cytokines secreted majorly by CMs. RNA analysis revealed 15 secretome-related transcripts that were more abundantly expressed in CMs compared to the other 2 cell types, including serpin family F member 1 (SERPINF1) (coding for pigment epithelium-derived factor; PEDF) and secreted phosphoprotein 1 (SPP1) (coding for osteopontin). At the protein level, the expression of osteopontin and PEDF was higher in CMs of different age groups compared to CFs and RPE cells. In the 3D models containing CMs, cytokine arrays also identified macrophage inflammatory protein (MIP)-1α/MIP-1β in non-stressed, MIP-1α/MIP-1β, interleukin (IL)-24, and angiogenin following an acute oxidative stress, and macrophage migration inhibitory factor (MIF), granulocyte-colony stimulating factor (G-CSF), intercellular adhesion molecule-1 (ICAM-1), and IL-1α following a chronic oxidative stress. This study identifies for the first time trophic factors secreted by CMs that could influence neighboring cells through paracrine signaling. Of those, PEDF and osteopontin are antioxidative proteins that are known to attenuate oxidative stress damage. Identifying factors that can help manage oxidative stress in the posterior segment of the eye may lead to promising treatments for retinal diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110125"},"PeriodicalIF":3.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyue Wang , Jinmiao Li , Jiahe Nie, Weifeng Huang, Junjie Tang, Yue Peng, Yang Gao, Rong Lu
{"title":"IL-33 protects retinal structure and function via mTOR/S6 signaling pathway in optic nerve crush","authors":"Xinyue Wang , Jinmiao Li , Jiahe Nie, Weifeng Huang, Junjie Tang, Yue Peng, Yang Gao, Rong Lu","doi":"10.1016/j.exer.2024.110121","DOIUrl":"10.1016/j.exer.2024.110121","url":null,"abstract":"<div><div>This study demonstrated the functions and molecular mechanisms of the IL-33/ST2 axis in experimental optic neuropathy. C57BL/6J mice were used to establish an optic nerve crush (ONC) model. ONC mice were administered with IL-33 intraperitoneal injection, with PBS vehicle as control. Immunofluorescence, quantitative RT-PCR, and western blot techniques were utilized to assess the expression of the IL-33/ST2 axis. The electroretinography (ERG), optical coherence tomography (OCT), H&E, and luxol fast blue were used to assess the structural and functional changes. Western blot was employed to detect the activation of the mTOR/S6 pathway. The IL-33 expression level in the inner nuclear layer of the retina in ONC mice reached its peak on day 3, accompanied by a significant increase in IL-33 receptor ST2 expression. IL-33 treatment promoted the survival of retinal ganglion cells, restored the thickness of inner retina layer (IRL), alleviated the demyelination of the optic nerve, and recovered the decreased amplitude of b-wave in ONC mice. Furthermore, administration of IL-33 activated the mTOR/S6 signaling pathway in RGCs, which was significantly suppressed in the ONC condition. This study indicated that boosting the IL-33/ST2/mTOR/S6 pathway can protect against structural and functional damage to the retina and optic nerve induced by ONC. As a result, the IL-33/ST2 axis holds potential as a therapeutic option for treating various optic neuropathies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110121"},"PeriodicalIF":3.0,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptomic analysis of keratoconus in Han Chinese patients: Insights into differential gene expression and ethnic-specific patterns","authors":"Yue Li , Yiqin Dai , Jianjiang Xu , Jing Zhang","doi":"10.1016/j.exer.2024.110118","DOIUrl":"10.1016/j.exer.2024.110118","url":null,"abstract":"<div><div>Keratoconus (KC) is a progressive corneal ectatic disorder with a high prevalence among Asians. This study aimed to explore the differential gene expression patterns in Han Chinese patients with KC, focusing on mRNAs and long noncoding RNAs (lncRNAs), to provide insights into the pathogenesis of the disease.</div><div>Corneal tissues from KC patients and healthy controls were collected, and RNA sequencing was performed to profile mRNA and lncRNA expression. A total of 1973 differentially expressed mRNAs (DEGs) and 386 differentially expressed lncRNAs (DELs) were identified in KC-affected corneas. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant enrichment in pathways related to ECM modulation, PI3K-Akt pathway and calcium signaling pathway. Furthermore, protein-protein interaction (PPI) network highlighted hub genes involved in ECM remodeling and inflammatory responses. Co-expression analysis of lncRNAs and mRNAs further prioritized 13 DELs linked to these hub genes. RT-qPCR validation confirmed the differential expression of select candidates. A meta-analysis integrating seven datasets from diverse ethnic backgrounds was performed and it suggested ethnic-specific differences in gene expression patterns.</div><div>This study sheds new light on the molecular mechanisms underlying KC in the Han Chinese population, pinpointing potential therapeutic targets. It also emphasizes the critical role of ethnic-specific gene expression patterns in KC research, highlighting a need for tailored approaches in disease management and treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110118"},"PeriodicalIF":3.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengmeng Yu , Huilin Chen , Chen Chen , Can Zhao , Qingjun Zhou , Lixin Xie , Ting Wang
{"title":"Hyperglycemia-depleted glutamine contributes to the pathogenesis of diabetic corneal endothelial dysfunction","authors":"Mengmeng Yu , Huilin Chen , Chen Chen , Can Zhao , Qingjun Zhou , Lixin Xie , Ting Wang","doi":"10.1016/j.exer.2024.110124","DOIUrl":"10.1016/j.exer.2024.110124","url":null,"abstract":"<div><div>Diabetic mellitus (DM) causes various complications, including the corneal endothelial dysfunction that leads to corneal edema and vision loss, especially in the DM patients with intraocular surgeries. However, the pathogenic mechanism of hyperglycemia-caused corneal endothelial dysfunction remains incomplete understood. Here we firstly screened and identified the glutamine contents of aqueous humor (AH) were significantly reduced in the type 2 diabetic patients and type 1 and type 2 diabetic mice. To explore the potential therapeutic effects of glutamine (Gln) supplement on the protection of diabetic corneal endothelial dysfunction, we performed the anterior chamber perfusion with the addition of L-alanyl-L-glutamine (Ala-Gln), and confirmed that Ala-Gln supplement not only accelerated the resolution of corneal edema and recovery of corneal thickness, but also preserved the regular arrangement and barrier-pump function of cornea. Mechanistically, we revealed that the supplements of Ala-Gln protect corneal endothelial cells (CECs) from the deleterious effects of high glucose-induced oxidative stress, mitochondrial dysfunction, and cell apoptosis. Overall, these results indicate the Gln depletion plays an important role in the diabetic corneal endothelial dysfunction, while the Ala-Gln supplement during intraocular surgery provide an effective prevention strategy through regulating the redox homeostasis and mitochondrial function of corneal endothelium.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110124"},"PeriodicalIF":3.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Tahvildari , Rao Me , Mizumi Setia , Nan Gao , Pratima Suvas , Sharon A. McClellan , Susmit Suvas
{"title":"Foxp3+ regulatory T cells reside within the corneal epithelium and co-localize with limbal stem cells","authors":"Maryam Tahvildari , Rao Me , Mizumi Setia , Nan Gao , Pratima Suvas , Sharon A. McClellan , Susmit Suvas","doi":"10.1016/j.exer.2024.110123","DOIUrl":"10.1016/j.exer.2024.110123","url":null,"abstract":"<div><div>In this study we investigated the presence of resident Foxp3<sup>+</sup> regulatory T cells (Tregs) within the cornea and assessed the role of resident Tregs in corneal epithelial wound healing. Using a mouse model, we showed that in the steady state Foxp3<sup>+</sup>Tregs are either in close proximity or co-localize with ABCG2<sup>+</sup> limbal stem cells. We also showed that these Tregs reside within the epithelial layer and not the corneal stroma. In addition, using a mouse model of mechanical injury, we demonstrated that depletion of Tregs from the cornea prior to corneal mechanical injury, using subconjunctival injection of anti-CD25, was associated with delayed epithelial healing. These results suggest a role for cornea resident Tregs in corneal epithelial cell function and wound healing and opens doors for further exploration of the role of Tregs in limbal stem cell function and survival.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110123"},"PeriodicalIF":3.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}