Ocular Surface最新文献

{"title":"Comparative analysis of long-term results of three epithelial cell transplantation procedures for treating limbal stem cell deficiency","authors":"Sathiya Kengpunpanich ,&nbsp;Chareenun Chirapapaisan ,&nbsp;Panotsom Ngowyutagon ,&nbsp;Suksri Chotikavanich ,&nbsp;Rosanun Sikarinkul ,&nbsp;Nuttacha Taetrongchit ,&nbsp;Simaporn Setthawong ,&nbsp;Pinnita Prabhasawat","doi":"10.1016/j.jtos.2024.01.003","DOIUrl":"10.1016/j.jtos.2024.01.003","url":null,"abstract":"<div><p>This study compared the long-term outcome of different epithelial transplantation techniques to treat limbal stem cell deficiency (LSCD). We conducted a retrospective 15-year comparative systematic cohort study of patients with LSCD who underwent either cultivated limbal epithelial transplantation (CLET), simple limbal epithelial transplantation (SLET), or cultivated oral mucosal epithelial transplantation (COMET). We reviewed the demographic data, etiology, LSCD severity, best-corrected visual acuity, surgical outcomes, and complications. A total of 103 eyes of 94 patients (mean age, 45.0 ± 16.4 years) with LSCD were enrolled. The most common cause of LSCD was chemical injury (42.7 %). The median follow-up time was 75 months. The success rates of CLET, SLET, and COMET were 45.5 %, 77.8 %, and 57.8 %, respectively. The 7-year survival rates after CLET, SLET, and COMET were 50.0 %, 72.2 %, and 53.2 %, respectively. Steven-Johnson syndrome (SJS) had a significantly lower survival rate than other causes (p &lt; 0.001), but SLET had a significantly higher survival rate than CLET (p = 0.018) and COMET (p = 0.047). Visual improvement of more than four Snellen lines was achieved in 53.1 % of successful cases and 28.2 % of failed cases. SJS, Schirmer I test &lt;5 mm, and the presence of postoperative recurrent epithelial defects were significant risk factors for a failed surgery. All epithelial transplantation techniques had favorable long-term surgical outcomes. More than half of the patients achieved a stable ocular surface and visual acuity improvement up to 7 years postoperatively. SLET tends to have a better surgical outcome than CLET and COMET, especially in patients with SJS.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 71-80"},"PeriodicalIF":6.4,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S154201242400003X/pdfft?md5=5ec3e67310c57e26775baba48a548914&pid=1-s2.0-S154201242400003X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139436786","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}

{"title":"Self-complementary AAV vector therapy for treating corneal cloudiness of mucopolysaccharidosis type VII (MPS VII)","authors":"Jhuwala Venkatakrishnan ,&nbsp;Yong Yuan ,&nbsp;Jianhua Zhang ,&nbsp;Yang Yu ,&nbsp;Yueh-Chiang Hu ,&nbsp;Winston W-Y Kao","doi":"10.1016/j.jtos.2024.01.002","DOIUrl":"10.1016/j.jtos.2024.01.002","url":null,"abstract":"<div><h3>Purpose</h3><p>To design a novel efficacious <em>scAAV-Gusb</em><span> viral vector for treating Mucopolysaccharidosis Type VII (MPS VII) caused by a mutation in the </span><em>β-Glu</em> gene (<em>Gusb</em> allele).</p></div><div><h3>Methods</h3><p>β-Glu expression of single-stranded <em>AAV-Gusb</em> (<em>ssAAV-Gusb</em><span>) and self-complementary AAV (</span><em>scAAV-Gusb</em>) vectors are tested with cultured murine <em>Gusb</em> fibroblasts. The <em>scAAV-Gusb</em><span> vector was chosen in further studies to prolong the life span and treat corneal pathology of </span><em>Gusb</em><span><span> mice via intrahepatic injection<span> of neonates and intrastromal injection in adults, respectively. Corneal pathology was studied using HRT2 in vivo </span></span>confocal microscope<span> and histochemistry in mice corneas.</span></span></p></div><div><h3>Results</h3><p>Both <em>ssAAV-Gusb</em> and <em>scAAV-Gusb</em> vectors expressed murine β-Glu in cultured <em>Gusb</em> fibroblasts. The <em>scAAV-Gusb</em> vector had higher transduction efficiency than the <em>ssAAV-Gusb</em> vector. To prolong the life span of <em>Gusb</em> mice, neonates (3 days old) were administered with <em>scAAV-Gusb</em><span> virus<span> via intrahepatic injection. The treatment improves the survival rate of </span></span><em>Gusb</em> mice, prolonging the median survival rate from 22.5 weeks (untreated) to 50 weeks (treated). Thereafter, we determined the efficacy of the <em>scAAV-Gusb</em> virus in ameliorating corneal cloudiness observed in aged <em>Gusb</em><span><span> mice. Both corneal cloudiness and stroma thickness decreased, and there was the presence of β-Glu </span>enzyme activity in the </span><em>Gusb</em> corneas receiving <em>scAAV-Gusb</em><span><span> virus associated with morphology change of amoeboid stromal cells in untreated to characteristic dendritic </span>keratocytes morphology after 4–12 weeks of </span><em>scAAV-Gusb</em> virus injection.</p></div><div><h3>Conclusion</h3><p>Intrahepatic injection of <em>scAAV-Gusb</em> is efficacious in prolonging the life span of <em>Gusb</em><span> mice, and intrastromal injection can ameliorate corneal phenotypes. Both strategies can be adapted for treating other MPS.</span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 39-47"},"PeriodicalIF":6.4,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139436740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-targeted and localized AAV5-DCN and AAV5-PEDF combination gene therapy abrogates corneal fibrosis and concurrent neovascularization in rabbit eyes in vivo","authors":"Rajiv R. Mohan ,&nbsp;Suneel Gupta ,&nbsp;Rajnish Kumar ,&nbsp;Nishant R. Sinha ,&nbsp;James Landreneau ,&nbsp;Prashant R. Sinha ,&nbsp;Ashish Tandon ,&nbsp;Shyam S. Chaurasia ,&nbsp;Nathan P. Hesemann","doi":"10.1016/j.jtos.2024.01.001","DOIUrl":"10.1016/j.jtos.2024.01.001","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span><span>Corneal fibrosis and </span>neovascularization (CNV) after ocular trauma impairs vision. This study tested therapeutic potential of tissue-targeted adeno-associated virus5 (AAV5) mediated </span>decorin (DCN) and pigment epithelium-derived factor (PEDF) combination genes </span><em>in vivo</em>.</p></div><div><h3>Methods</h3><p><span><span>Corneal fibrosis and CNV were induced in New Zealand White rabbits via chemical trauma. Gene therapy in stroma was delivered 30-min after chemical-trauma via topical AAV5-DCN and AAV5-PEDF application using a cloning cylinder. Clinical eye examinations and </span>multimodal imaging in live rabbits were performed periodically and corneal tissues were collected 9-day and 15-day post euthanasia. Histological, cellular, and molecular and </span>apoptosis assays were used for efficacy, tolerability, and mechanistic studies.</p></div><div><h3>Results</h3><p><span><span>The AAV5-DCN and AAV5-PEDF combination gene therapy significantly reduced corneal fibrosis (p &lt; 0.01 or p &lt; 0.001) and CNV (p &lt; 0.001) in therapy-given (chemical-trauma and AAV5-DCN + AAV5-PEDF) rabbit eyes compared to the no-therapy given eyes (chemical-trauma and AAV5-naked vector). Histopathological analyses demonstrated significantly reduced fibrotic α-smooth muscle actin and endothelial lectin expression in therapy-given corneas compared to no-therapy corneas on day-9 (p &lt; 0.001) and day-15 (p &lt; 0.001). Further, therapy-given corneas showed significantly increased Fas-ligand mRNA levels (p &lt; 0.001) and </span>apoptotic cell death in neovessels (p &lt; 0.001) compared to no-therapy corneas. AAV5 delivered 2.69 × 10</span>⁷ copies of DCN and 2.31 × 10⁷ copies of PEDF genes per μg of DNA. AAV5 vector and delivered DCN and PEDF genes found tolerable to the rabbit eyes and caused no significant toxicity to the cornea.</p></div><div><h3>Conclusion</h3><p>The combination AAV5-DCN and AAV5-PEDF topical gene therapy effectively reduces corneal fibrosis and CNV with high tolerability <em>in vivo</em> in rabbits. Additional studies are warranted.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 13-25"},"PeriodicalIF":6.4,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139112016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A closer look into the cellular and molecular biology of myoepithelial cells across various exocrine glands","authors":"Olivier Mauduit ,&nbsp;Vanessa Delcroix ,&nbsp;Andrew Wong ,&nbsp;Anastasiia Ivanova ,&nbsp;Lindsey Miles ,&nbsp;Hyun Soo Lee ,&nbsp;Helen Makarenkova","doi":"10.1016/j.jtos.2023.12.003","DOIUrl":"10.1016/j.jtos.2023.12.003","url":null,"abstract":"<div><p><span>Myoepithelial cells (MECs) are a unique subset of epithelial cells that possess several smooth muscle cell<span><span> characteristics, such as a high number of actin-myosin filaments and the ability to contract. These cells are primarily located around the secretory cells of </span>exocrine glands, including the salivary, mammary, lacrimal, and sweat glands. Their primary functions involve the construction of the </span></span>basement membrane and help with secretion of gland products through contraction. So far, no comparative analysis of MECs in different exocrine glands had ever evaluated their differences. In this review, we took advantage of the various publicly available scRNAseq data from mouse exocrine glands to identify their shared and unique characteristics.</p><p>The aim of this review is to compare the role of MECs in maintaining healthy glandular function, their involvement in disease states, and their regenerative capacity, with a particular emphasis on the latest research findings in these areas.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"31 ","pages":"Pages 63-80"},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling meibum secretion: Alternatives for obstructive Meibomian Gland Dysfunction (MGD)","authors":"Shangbang Luo ,&nbsp;Gagik P. Djotyan ,&nbsp;Rohan Joshi ,&nbsp;Tibor Juhasz ,&nbsp;Donald J. Brown ,&nbsp;James V. Jester","doi":"10.1016/j.jtos.2023.11.005","DOIUrl":"10.1016/j.jtos.2023.11.005","url":null,"abstract":"<div><h3>Purpose</h3><p><span>While changes in meibum quality are correlated with severity of meibomian gland dysfunction (MGD) and dry eye disease, little is known regarding the mechanics of meibum secretion. The purpose of this study was to develop a finite element model of meibum secretion and evaluate the effect of various factors that might impact meibum delivery to the </span>ocular surface.</p></div><div><h3>Methods</h3><p><span>A finite element analysis in COMSOL 6.0 was used to simulate the flow of meibum within the gland's terminal excretory duct. Historical normal human meibum </span>rheology data taken over the meibum melting range from fluid (35–40 °C) to solid (25–30 °C) were then used to calculate the minimum yield stress and plastic viscosity of meibum. The effects of meibum melting state, eyelid pressure and terminal duct diameter on meibum flow rates were then systematically investigated.</p></div><div><h3>Results</h3><p>The melting state of meibum from liquid to solid was associated with an increase in the minimum yield stress and plastic viscosity that caused an exponential decrease in meibum flow. Modeling also established that there was a linear correlation between meibum flow rate and eyelid pressure needed to express meibum and the 4th power of the terminal duct radius.</p></div><div><h3>Conclusions</h3><p>Our results suggest that changes in the melting state of meibum from fluid to solid, as well as changes in the radius of the terminal excretory duct and the force exerted by the eyelid can lead to dramatic decreases in the flow of meibum. Together these findings suggest alternative mechanisms for meibomian gland obstruction.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"31 ","pages":"Pages 56-62"},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic signatures of tear extracellular vesicles caused by herpes simplex keratitis","authors":"Huixiang Ma ,&nbsp;Tucan Chen ,&nbsp;Chengxu Li ,&nbsp;Hao Xu ,&nbsp;Qingyu Feng ,&nbsp;Yunfei Su ,&nbsp;Jianqiu Cai ,&nbsp;Qingfu Zhu ,&nbsp;Fei Liu ,&nbsp;Liang Hu","doi":"10.1016/j.jtos.2023.12.005","DOIUrl":"10.1016/j.jtos.2023.12.005","url":null,"abstract":"<div><h3>Purpose</h3><p>Herpes simplex keratitis<span> (HSK), caused by type 1 herpes simplex<span> virus (HSV) reactivation, is a severe infectious disease that leads to vision loss. HSV can trigger metabolic reprogramming in the host cell and change the extracellular vesicles (EV) cargos; however, little is known about the EV metabolic signatures during ocular HSV infection. Here, we aimed to depict the EV-associated metabolic landscape in HSK patients’ tears.</span></span></p></div><div><h3>Methods</h3><p>We collected 82 samples from 41 participants with unilateral HSK (contralateral unaffected tears were set as negative control), including subtype cohorts of 13 epithelial, 20 stromal, and 8 endothelial HSK. We isolated tear EVs via our previously established platform and conducted metabolic analysis using LC-MS/MS. The metabolic signatures for recognizing HSK and subtypes were assessed through differential analysis and machine learning algorithms.</p></div><div><h3>Results</h3><p>Hypopsia and increased extracellular CD63 levels were observed in affected eyes. We identified 339 metabolites based on sEVs isolated from tears. Differential analysis revealed alterations in energy and amino acid metabolism<span><span>, as well as the infectious microenvironment. Furthermore, we observed dysregulated metabolite such as methyldopa, which is associated with inappropriate </span>neovascularization and corneal sensation loss, contributing to the HSK severity particularly in the stromal subtype. Moreover, machine learning classification also suggested a set of EV metabolic signatures that have potential for pan-keratitis detection.</span></p></div><div><h3>Conclusions</h3><p>Our findings demonstrate that tear EV metabolites can serve as valuable indicators for comprehending the underlying pathological mechanisms. This knowledge is expected to facilitate the development of liquid biopsy means and therapeutic target discovery.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"31 ","pages":"Pages 21-30"},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138739993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression changes in conjunctival cells associated with contact lens wear and discomfort","authors":"Andrés Ángel Calderón-García ,&nbsp;Laura Valencia-Nieto ,&nbsp;Cristina Valencia-Sandonis ,&nbsp;Alberto López-de la Rosa ,&nbsp;Marta Blanco-Vazquez ,&nbsp;Itziar Fernández ,&nbsp;Carmen García-Vázquez ,&nbsp;Cristina Arroyo-del Arroyo ,&nbsp;María J. González-García ,&nbsp;Amalia Enríquez-de-Salamanca","doi":"10.1016/j.jtos.2023.12.004","DOIUrl":"10.1016/j.jtos.2023.12.004","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to analyze the differences in the expression of pain-related genes in conjunctival epithelial cells among symptomatic contact lens (CL) wearers (SCLWs), asymptomatic CL wearers (ACLWs), and non-CL wearers (non-CLWs).</p></div><div><h3>Methods</h3><p>For this study, 60 participants (20 non-CLWs, 40 CLWs) were enrolled. The CLW group comprised 20 ACLWs and 20 SCLWs according to the Contact Lens Dry Eye Questionnaire short form©. Conjunctival cells were collected using impression cytology, and RNA was isolated and used to determine the expression levels of 85 human genes involved in neuropathic and inflammatory pain. The effects of CL wear and discomfort were evaluated using mixed-effects ANOVA with partially nested fixed-effects model. Gene set enrichment analysis was performed to assign biological meaning to sets of differentially expressed genes.</p></div><div><h3>Results</h3><p>Six genes (<em>CD200</em>, <em>EDN1</em>, <em>GRIN1</em>, <em>PTGS1</em>, <em>P2RX7,</em> and <em>TNF</em>) were significantly upregulated in CLWs compared to non-CLWs. Eleven genes (<em>ADORA1</em>, <em>BDKRB1</em>, <em>CACNA1B</em>, <em>DBH</em>, <em>GRIN1</em>, <em>GRM1</em>, <em>HTR1A</em>, <em>PDYN</em>, <em>PTGS1</em>, <em>P2RX3,</em> and <em>TNF</em>) were downregulated in SCLWs compared to ACLWs. These genes were mainly related to pain, synaptic transmission and signaling, ion transport, calcium transport and concentration, and cell-cell signaling.</p></div><div><h3>Conclusions</h3><p>CL wear modified the expression of pain- and inflammation-related genes in conjunctival epithelial cells. These changes may be in part, along with other mechanisms, responsible for CL discomfort in SCLWs.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"31 ","pages":"Pages 31-42"},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012423001556/pdfft?md5=af9c6720a2a3045c707861487687aaba&pid=1-s2.0-S1542012423001556-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138833809","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}

{"title":"Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy","authors":"Martin Schicht ,&nbsp;Jessica Farger ,&nbsp;Saskia Wedel ,&nbsp;Marco Sisignano ,&nbsp;Klaus Scholich ,&nbsp;Gerd Geisslinger ,&nbsp;Natarajan Perumal ,&nbsp;Franz H. Grus ,&nbsp;Swati Singh ,&nbsp;Afsun Sahin ,&nbsp;Friedrich Paulsen ,&nbsp;Elke Lütjen-Drecoll","doi":"10.1016/j.jtos.2023.12.006","DOIUrl":"10.1016/j.jtos.2023.12.006","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral </span>polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear.</p></div><div><h3>Methods</h3><p><span>In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, </span>dorsal root<span> and trigeminal ganglia<span><span> with the changes in the ocular surface, including tear </span>proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.</span></span></p></div><div><h3>Results</h3><p>The lacrimal gland<span><span>, conjunctival goblet cells and cornea showed morphological changes along with alterations in </span>tear proteins<span><span><span> without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of </span>Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and </span>Pigr<span> in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia<span><span> neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases<span> and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating </span></span>chemokines.</span></span></span></span></p></div><div><h3>Conclusion</h3><p>The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment<span> could delay or even prevent the ocular complications of DM such as DED and PN.</span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"31 ","pages":"Pages 43-55"},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous TSG-6 modulates corneal inflammation following chemical injury","authors":"Sudhir Verma ,&nbsp;Isabel Y. Moreno ,&nbsp;Cassio Prinholato da Silva ,&nbsp;Mingxia Sun ,&nbsp;Xuhong Cheng ,&nbsp;Tarsis F. Gesteira ,&nbsp;Vivien J. Coulson- Thomas","doi":"10.1016/j.jtos.2023.12.007","DOIUrl":"10.1016/j.jtos.2023.12.007","url":null,"abstract":"<div><h3>Purpose</h3><p>Tumor necrosis factor<span> (TNF)-stimulated gene-6 (TSG-6) is upregulated in various pathophysiological contexts, where it has a diverse repertoire of immunoregulatory functions. Herein, we investigated the expression and function of TSG-6 during corneal homeostasis and after injury.</span></p></div><div><h3>Methods</h3><p><span>Human corneas, eyeballs from BALB/c (</span><em>TSG-6</em>^<em>+/+</em>), <em>TSG-6⁺</em>^<em>/</em>⁻ and <em>TSG-6</em>^{<em>−/−</em>}<span><span> mice, human immortalized corneal epithelial cells and murine corneal epithelial progenitor cells were prepared for immunostaining and </span>real time PCR<span><span> analysis of endogenous expression of TSG-6. Mice were subjected to unilateral corneal debridement or alkali burn (AB) injuries and wound healing assessed over time using </span>fluorescein stain, </span></span><em>in vivo</em><span> confocal microscopy and histology.</span></p></div><div><h3>Results</h3><p><span>TSG-6 is endogenously expressed in the human and mouse cornea and established corneal epithelial cell lines and is upregulated after injury. A loss of TSG-6 has no structural and functional effect in the cornea during homeostasis. No differences were noted in the rate of corneal epithelial wound closure between BALB/c, </span><em>TSG-6</em>⁺^<em>/</em>⁻ and <em>TSG-6</em>^{<em>−/−</em>} mice. <em>TSG-6</em>^{<em>−/−</em>}<span> mice presented decreased inflammatory response within the first 24 h of injury and accelerated corneal wound healing following AB when compared to control mice.</span></p></div><div><h3>Conclusion</h3><p>TSG-6 is endogenously expressed in the cornea and upregulated after injury where it propagates the inflammatory response following chemical injury.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 26-38"},"PeriodicalIF":6.4,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139034825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A PEDF peptide mimetic effectively relieves dry eye in a diabetic murine model by restoring corneal nerve, barrier, and lacrimal gland function","authors":"Shuangping Chen ,&nbsp;Colin James Barnstable ,&nbsp;Xiaomin Zhang ,&nbsp;Xiaorong Li ,&nbsp;Shaozhen Zhao ,&nbsp;Joyce Tombran-Tink","doi":"10.1016/j.jtos.2023.12.002","DOIUrl":"10.1016/j.jtos.2023.12.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span>The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using </span>streptozotocin.</p></div><div><h3>Methods</h3><p><span><span><span>Mice were treated topically for 3–6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury<span> were measured using Cochet-Bonnet esthesiometer, </span></span>phenol red cotton thread wetting, </span>fluorescein sodium<span> staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the </span></span>lacrimal glands were measured.</p></div><div><h3>Results</h3><p>Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion<span><span> and increased corneal epithelium<span> injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1β and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide </span></span>treatment.</span></p></div><div><h3>Conclusion</h3><p>The study demonstrates that topical application<span> of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.</span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 1-12"},"PeriodicalIF":6.4,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138713963","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}