Experimental eye research最新文献

{"title":"The role of nicotinamide riboside in the preservation of retinal ganglion cells using an in vitro glutamate-induced excitotoxicity model","authors":"Nan Zhang ,&nbsp;Dongxiao Ji ,&nbsp;Yixin Hu ,&nbsp;Pengyu Zhang ,&nbsp;Xizhi Deng ,&nbsp;Min Zhu ,&nbsp;Wen Zeng ,&nbsp;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 ,&nbsp;Solange Landreville ,&nbsp;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}

{"title":"IL-33 protects retinal structure and function via mTOR/S6 signaling pathway in optic nerve crush","authors":"Xinyue Wang ,&nbsp;Jinmiao Li ,&nbsp;Jiahe Nie,&nbsp;Weifeng Huang,&nbsp;Junjie Tang,&nbsp;Yue Peng,&nbsp;Yang Gao,&nbsp;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&amp;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 ,&nbsp;Yiqin Dai ,&nbsp;Jianjiang Xu ,&nbsp;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}

{"title":"Hyperglycemia-depleted glutamine contributes to the pathogenesis of diabetic corneal endothelial dysfunction","authors":"Mengmeng Yu ,&nbsp;Huilin Chen ,&nbsp;Chen Chen ,&nbsp;Can Zhao ,&nbsp;Qingjun Zhou ,&nbsp;Lixin Xie ,&nbsp;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}

{"title":"Foxp3+ regulatory T cells reside within the corneal epithelium and co-localize with limbal stem cells","authors":"Maryam Tahvildari ,&nbsp;Rao Me ,&nbsp;Mizumi Setia ,&nbsp;Nan Gao ,&nbsp;Pratima Suvas ,&nbsp;Sharon A. McClellan ,&nbsp;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⁺ 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⁺Tregs are either in close proximity or co-localize with ABCG2⁺ 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}

{"title":"Experimental models for keratoconus: Insights and challenges","authors":"Sujithra Shankar ,&nbsp;Rashmi Deshmukh ,&nbsp;Tejaswini Pingali ,&nbsp;Rohini Sonar ,&nbsp;Sayan Basu ,&nbsp;Vivek Singh","doi":"10.1016/j.exer.2024.110122","DOIUrl":"10.1016/j.exer.2024.110122","url":null,"abstract":"<div><div>Keratoconus, a progressive corneal disorder characterized by the thinning and conical protrusion of the cornea because of collagen degradation, poses significant challenges to both clinicians and researchers. Most successful animal models of keratoconus are based on genetic mutations and knock-outs in mice and rats that hinder normal corneal stromal architecture, thickness, or strength. While mice and rat models are suitable to study the molecular mechanism and physiological changes to the cornea, they are not suitable for experimental research; especially for surgical interventions like: deep anterior lamellar keratoplasty (DALK), stromal lenticule addition keratoplasty, and other advanced therapies. This review article comprehensively examines recent advancements in experimental models for keratoconus, focusing on their potential for translational research and the challenges ahead. It explores the historical context of experimental models, focusing on animal-based models, mainly rabbits in particular. These advancements enable researchers to mimic the biomechanical and biochemical alterations observed in keratoconic corneas. While these models offer valuable insights into disease mechanisms and treatment development, several challenges remain in transforming experimental findings into clinical applications.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110122"},"PeriodicalIF":3.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441520","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":"CYSLTR1 antagonism displays potent anti-tumor effects in uveal melanoma","authors":"Paulina García de Alba Graue ,&nbsp;Mohamed Abdouh ,&nbsp;Alicia Goyeneche ,&nbsp;Julia Valdemarin Burnier ,&nbsp;Miguel N. Burnier","doi":"10.1016/j.exer.2024.110120","DOIUrl":"10.1016/j.exer.2024.110120","url":null,"abstract":"<div><div>Uveal Melanoma (UM) is the most common primary intraocular malignancy in adults. Although rare, it is a deadly tumor, with a long-term prognosis of death occurring in more than 50% of the cases. It is characterized by frequent (∼80%) driver mutations in GNAQ and GNA11 genes, both of which are activated by cysteinyl leukotriene receptors (CYSLTRs). CYSLTR1 is upregulated and participated in the progression of several cancers. In the present study, we sought to determine the expression levels of CYSLTR1 in 31 human UM specimens and cell lines (3 primary and 1 metastatic), and its role in the proliferation and viability of these cells by analyzing cell metabolic activity, cell confluence and apoptosis levels. We show that all analyzed UM specimens and cells expressed CYSLTR1 at high levels. Notably, the pharmacological blockage of this receptor, using the inverse agonist MK571, reduced the growth and metabolic activity, and increased the apoptotic cell death of all analyzed UM cell lines. We provide evidence that CYSLTR1 is expressed in human UM and plays a significant role in UM progression behavior. Our data highlight the potential beneficial effects of targeting CYSLTR1 in the control of UM progression.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110120"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399856","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":"Comment on: “Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction”","authors":"David Fernando Lara-Santofimio,&nbsp;Francisco J. Bonilla-Escobar","doi":"10.1016/j.exer.2024.110119","DOIUrl":"10.1016/j.exer.2024.110119","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110119"},"PeriodicalIF":3.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389210","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":"The influence of polyacrylamide gel substrate elasticity on primary cultures of rat retinal ganglion cells","authors":"Matthias Strake ,&nbsp;Charlotte V. Fischer-Wedi ,&nbsp;Mohammed H. Khattab ,&nbsp;Peer Lauermann ,&nbsp;Carina Wollnik ,&nbsp;Christina Stanischa ,&nbsp;Hans Hoerauf ,&nbsp;Florian Rehfeldt ,&nbsp;Christian van Oterendorp","doi":"10.1016/j.exer.2024.110116","DOIUrl":"10.1016/j.exer.2024.110116","url":null,"abstract":"<div><div>In vitro primary cell culture models of retinal ganglion cells (RGC) are widely used to study pathomechanisms of diseases such as glaucoma. The biomechanic interaction with the culture substrate is known to influence core cellular functions. RGC cultures, however, are usually grown on rigid plastic or glass substrates. We hypothesized that soft polyacrylamide gel substrates may alter survival and neurite outgrowth of primary cultured RGC.</div><div>Primary retinal cultures from postnatal (day 1–6) Wistar rats were grown on glass coverslips or polyacrylamide (PA) gel substrate with different Young's elastic moduli (0.75, 10 or 30 kPa). Substrates were coated with Poly-l-lysine and/or laminin. RGC were immunostained with anti-beta-III-tubulin. Total neurite length, growth cone morphology, RGC density, mitochondrial morphology and transport as well as pro-survival pathways (Erk1/2, Akt, CREB) were assessed.</div><div>PA gel substrates of E = 10 kPa significantly increased the total neurite length by factor 1.5 compared to glass (p = 0.02). The growth cone area was significantly larger by factor 5.3 on 30 kPa gels (p = 0.01). The presence of a substrate coating was more important for neurite outgrowth and RGC survival on PA gels (poly-l-lysine &gt; laminin) than on glass. Neither mitochondrial morphology and motility nor the activation of pro-survival pathways significantly differed between the four substrates.</div><div>PA gel substrates significantly enhanced RGC neurite outgrowth. The signaling cascades mediating this effect remain to be determined.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110116"},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389211","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}