Journal of Ocular Pharmacology and Therapeutics最新文献

{"title":"Detection of Residual iPSCs Following Differentiation of iPSC-Derived Retinal Pigment Epithelial Cells.","authors":"Matthew Hill, Cynthia Andrews-Pfannkoch, Evan Atherton, Travis Knudsen, Emma Trncic, Alan D Marmorstein","doi":"10.1089/jop.2024.0130","DOIUrl":"10.1089/jop.2024.0130","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> The goal of this study was to develop a lot release assay for iPSC residuals following directed differentiation of iPSCs to retinal pigment epithelial (RPE) cells. <b><i>Methods:</i></b> RNA Sequencing (RNA Seq) of iPSCs and RPE derived from them was used to identify pluripotency markers downregulated in RPE cells. Quantitative real time PCR (qPCR) was then applied to assess iPSC residuals in iPSC-derived RPE. The limit of detection (LOD) of the assay was determined by performing spike-in assays with known quantities of iPSCs serially diluted into an RPE suspension. <b><i>Results:</i></b> <i>ZSCAN10</i> and <i>LIN28A</i> were among 8 pluripotency markers identified by RNA Seq as downregulated in RPE. Based on copy number and expression of pseudogenes and lncRNAs <i>ZSCAN10</i> and <i>LIN28A</i> were chosen for use in qPCR assays for residual iPSCs. Reverse transcription PCR indicated generally uniform expression of <i>ZSCAN10</i> and <i>LIN28A</i> in 21 clones derived from 8 iPSC donors with no expression of either in RPE cells derived from 5 donor lines. Based on qPCR, <i>ZSCAN10</i>, and <i>LIN28A</i> expression in iPSCs was generally uniform. The LOD for <i>ZSCAN10</i> and <i>LIN28A</i> in qPCR assays was determined using spike in assays of RPE derived from 2 iPSC lines. Analysis of ΔΔC_t found the limit of detection to be <0.01% of cells, equivalent to <1 iPSC/10,000 RPE cells in both iPSC lines. <b><i>Conclusions:</i></b> qPCR for <i>ZSCAN10</i> and <i>LIN28A</i> detects <1 in 10,000 residual iPSCs in a population of iPSC-derived RPE providing an adequate LOD of iPSC residuals for lot release testing.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"680-687"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Rebamipide for Dry Eye on Optical Quality and Efficacy: A Systematic Review and Meta-Analysis.","authors":"Yu-Ling Yan, Jing-Yao Chang, Xin-Ru Ling, Chun-Yan Xue","doi":"10.1089/jop.2024.0098","DOIUrl":"10.1089/jop.2024.0098","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To evaluate the effects of rebamipide ophthalmic suspension on optical quality and efficacy of patients with dry eye under different conditions. <b><i>Methods:</i></b> A comprehensive search across five databases (PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wan Fang) was conducted for studies published through May 13, 2024, focusing on rebamipide for dry eye treatment. <b><i>Results:</i></b> A total of 11 studies including 334 patients with dry eye were included. Tear breakup time (TBUT) values of patients with dry eye increased significantly after 2 weeks (standardized mean difference [SMD] =1.07, 95% confidence interval [CI] = [0.05, 2.09]), 4 weeks (SMD = 1.26, 95% CI = [0.77, 1.75]), and 12 weeks (SMD = 1.04, 95% CI = [0.37, 1.71]) of rebamipide treatment. Subgroup analysis revealed that patients with dry eye wearing soft contact lens (SCL) exhibited higher TBUT values after 4 weeks of rebamipide treatment compared with those who received rebamipide alone. In addition, rebamipide significantly improved fluorescein staining score of patients with dry eye after 4 weeks of treatment (SMD = -0.34, 95% CI = [-0.63, -0.06]). However, 4 weeks of rebamipide treatment showed no significant effect on Schirmer I test values (SMD = -0.04, 95%, CI = [-0.43, 0.35]) and higher-order aberrations (SMD = -0.73, 95% CI = [-1.77, 0.30]). <b><i>Conclusions:</i></b> These results indicate a significant improvement in the efficacy of rebamipide treatment for patients with dry eye, particularly for those wearing SCL. The effect of rebamipide on visual quality was found to correlate with the underlying dry eye status.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"629-637"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation in Dry Eye Disease-Pathogenesis, Preclinical Animal Models, and Treatments.","authors":"Santosh Bhujbal, Ilva D Rupenthal, Philipp Steven, Priyanka Agarwal","doi":"10.1089/jop.2024.0103","DOIUrl":"10.1089/jop.2024.0103","url":null,"abstract":"<p><p>Dry eye disease (DED) is a rapidly growing ocular surface disease with a significant socioeconomic impact that affects the patients' visual function and, thus, their quality of life. It is distinguished by a loss of tear film homeostasis, leading to tear film instability, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities, with all of these playing etiological roles in the propagation of the vicious DED circle. While current treatments primarily focus on reducing tear film instability and hyperosmolarity, increasingly more attention is being placed on tackling the underlying inflammation that propagates and potentiates these factors. As such, preclinical models are crucial to further elucidate the DED pathophysiology and develop novel therapeutic strategies. This review outlines the role of inflammation in DED, highlighting related signs and diagnostic tools before focusing on relevant preclinical animal models and potential therapeutic strategies to tackle DED-associated inflammation.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"638-658"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway.","authors":"Jin Sun Hwang, Hyun Beom Song, Geonhui Lee, Sangmoo Jeong, Dae Joong Ma","doi":"10.1089/jop.2024.0064","DOIUrl":"10.1089/jop.2024.0064","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To examine the potential protective effects of adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASC-EVs) on ARPE-19 cells exposed to hydrogen peroxide (H₂O₂) stress and to evaluate their ability to delay retinal degeneration in Royal College of Surgeons (RCS) rats. <b><i>Methods:</i></b> ARPE-19 cells were pre-treated with ASC-EVs for 24 h, followed by exposure to 200 μM H₂O₂ for an additional 24 h. RCS rats received an intravitreal injection of phosphate-buffered saline in one eye and ASC-EVs in the other eye. <b><i>Results:</i></b> ASC-EV pretreatment significantly protected against H₂O₂ in the Cell Counting Kit-8 assay and was also effective in the lactate dehydrogenase-release assay. It notably reduced early apoptosis (Annexin V-fluorescein isothiocyanate/propidium iodide assay) and late apoptosis (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay), while significantly decreasing intracellular reactive oxygen species, glutathione levels, and superoxide dismutase activity. <i>NFE2L2</i>, <i>HMOX1</i>, and <i>NQO1</i> mRNA levels, along with Nrf2, HO-1, and NQO1 protein levels, were significantly elevated with ASC-EV pretreatment. Compared with ARPE-19-derived EVs, 11 miRNAs were upregulated and 34 were downregulated in ASC-EVs. In RCS rats, intravitreal injections of ASC-EVs led to significant preservation of the outer nuclear layer and photoreceptor segments, along with increased nuclear Nrf2 expression and elevated HO-1 and NQO1 levels in the inner retina. Eyes that received intravitreal injections of ASC-EVs demonstrated significantly preserved electroretinography a- and b-wave amplitudes at 1 week post-injection, though this effect faded by 2 weeks. <b><i>Conclusions:</i></b> ASC-EVs mitigated apoptosis and oxidative stress in ARPE-19 cells subjected to H₂O₂ exposure and temporarily slowed retinal degeneration in RCS rats via Nrf2 pathway activation by miRNAs.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"688-701"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eyes on New Product Development.","authors":"Gary D Novack","doi":"10.1089/jop.2024.0155","DOIUrl":"10.1089/jop.2024.0155","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"543-544"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of a Preservative-Free Latanoprost Cationic Emulsion in Patients with Open-Angle Glaucoma and Concurrent Ocular Surface Disease: A Randomized Phase 2 Study.","authors":"Jason Bacharach, Eugene B McLaurin, Steven Silverstein, Mourad Amrane, Jean-Sebastien Garrigue, Dahlia Ismail, William J Flynn","doi":"10.1089/jop.2024.0029","DOIUrl":"10.1089/jop.2024.0029","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To compare intraocular pressure (IOP), ocular surface disease (OSD) parameters, and safety in patients with open-angle glaucoma (OAG)/ocular hypertension (OH) and concurrent OSD treated with preservative-free latanoprost 0.005% cationic emulsion (PF-latanoprost-E) or travoprost-Z 0.004% ophthalmical solution containing a soft preservative system. <b><i>Methods:</i></b> Patients with OAG/OH and OSD were randomized to treatment with PF-latanoprost-E or travoprost-Z nightly for 3 months. Outcomes included mean diurnal IOP reduction; OSD endpoints, including symptom improvement, tear break-up time (TBUT), and corneal fluorescein staining (CFS) score; and safety after 1 and 3 months. <b><i>Results:</i></b> A total of 105 patients were randomized, 51 to PF-latanoprost-E and 54 to travoprost-Z. IOP reductions (LS mean differences) at 3 months were numerically greater in the PF-latanoprost-E than in the travoprost-Z group at 8AM (7.2 versus 6.0 mmHg), 10AM (6.7 versus 5.9 mmHg), and 4PM (6.0 versus 5.4 mmHg). LS mean changes in IOP from baseline in both groups at 1 and 3 months, however, were comparable. Mean ± SD CFS scores on the Ora scale at month 3 showed significantly greater reductions in the PF-latanoprost-E than in the travoprost-Z group (-1.07 ± 1.863 versus -0.16 ± 2.553 <i>P</i> = 0.0461). The mean TBUT at month 3 showed similar improvements in both groups (1.1 versus 1.0 s, <i>P</i> > 0.05). OSD symptoms improved but did not differ significantly in the two groups. Overall safety was comparable in both groups. <b><i>Conclusion:</i></b> PF-latanoprost-E effectively and safely lowered IOP and improved OSD parameters in patients with OAG/OH. These findings provide evidence for the beneficial effects of this new formulation of latanoprost in glaucoma patients with OSD.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"553-561"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuritin 1 Drives Therapeutic Preservation of Retinal Ganglion Cells in an <i>Ex Vivo</i> Human Glaucoma Model.","authors":"Shahna S Hameed, Nicole E Bodi, Ryan C Miller, Tasneem P Sharma","doi":"10.1089/jop.2024.0041","DOIUrl":"10.1089/jop.2024.0041","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Glaucoma is a leading cause of irreversible blindness. Glaucomatous intraocular pressure (IOP) triggers deleterious effects, including gliosis, optic nerve (ON) axonal retraction, neurotrophic factor deprivation, inflammation, and other pathological events, leading to retinal ganglion cell (RGC) loss. Trophic factor impairment enhances RGC apoptosis susceptibility. Neuritin 1 (NRN1), a neurotrophic protein downstream of various neurotrophins, exhibited RGC protection and regeneration in axotomy models. We evaluated human recombinant NRN1's impact on human RGCs cultured in pressurized conditions within the <i>ex vivo</i> translaminar autonomous system to simulate glaucoma pathogenesis. <b><i>Methods:</i></b> Human glaucomatous and non-glaucomatous donor eyes were obtained from eye banks according to the Declaration of Helsinki. Initially, we evaluated NRN1and RGC marker expression in glaucoma and non-glaucomatous retina to determine the NRN1 level and its association with RGC loss. Further, we evaluated NRN1's therapeutic potential by treating pressurized human eyes at normal and high IOP for seven days. Retina, ON, and conditioned medium were analyzed for RGC survival (<i>THY1</i>, <i>RBPMS</i>), gliosis (<i>GFAP</i>), apoptosis (<i>CASP3</i>, <i>CASP7</i>), and extracellular matrix deposition (COLIV, FN) by qRT-PCR and western blotting. Paraphenylenediamine staining assessed ON axonal degeneration, whereas ex <i>vivo</i> electroretinogram assessed retinal activity. <b><i>Results:</i></b> Glaucomatous retinas exhibited significant reductions in both NRN1 (<i>*p</i> = 0.007, <i>n</i> = 5) and RGC marker expression (<i>*p</i> = 0.04, <i>n</i> = 5). NRN1 treatment reduced gliosis, extracellular matrix deposition, ON degeneration, and increased retinal activity in pressure-perfused eyes. <b><i>Conclusions:</i></b> Our study confirms that NRN1 enhances human RGC survival and improves retinal function in degenerative conditions, substantiating it as a promising candidate for rescuing human RGCs from degeneration.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"596-607"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Ocular Pharmacokinetics of Dexamethasone Implants in Rabbits.","authors":"Jihyun Won, Juhyung Kang, Wonku Kang","doi":"10.1089/jop.2024.0052","DOIUrl":"10.1089/jop.2024.0052","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Dexamethasone eye implant has been used to treat macular edema and non-infectious uveitis. To date, its ocular pharmacokinetics are not fully characterized, and the development of generic preparations is in progress, as the patent of the original brand expires soon. Therefore, this work was designed to 1) determine the time course of vitreous dexamethasone concentrations following intravitreal implantation in rabbits and 2) explore the alternative use of NDF-SI01 from a pharmacokinetic point of view compared to Ozurdex^®, which is currentlyused in the market. <b><i>Methods:</i></b> Ozurdex^® and NDF-SI01 were implanted into the right and left eyes of the rabbit, respectively. A serial vitreous collection was performed to minimize the sacrifice of animals, and dexamethasone concentrations were measured by HP LC-MS/MS. <b><i>Results:</i></b> After implantation, dexamethasone concentration reaches the maximum concentration (3.1 μg/mL) in 19.5 days and decreases with a half-life of 40.3 h. AUC and clearance are 683.9 μg·h/mL and 1.29 mL/h, respectively. There is no significant difference in pharmacokinetic parameters between NDF-SI01 and Ozurdex^®. The overall patterns of the cumulative release of both implants are similar. <b><i>Conclusions:</i></b> NDF-SI01 could alternate Ozurdex^® in clinics based on the in vivo comparative pharmacokinetic study and in vitro dissolution test.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"608-614"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Human Meibum Lipid Composition Related to the Presence and Severity of Meibomian Gland Dysfunction.","authors":"Ashley Nguyen, Kugen K Naidoo, Layla Ajouz, Xiaoming Xu, Cathy Zhao, Michael R Robinson, Douglas Borchman","doi":"10.1089/jop.2024.0063","DOIUrl":"10.1089/jop.2024.0063","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Changes in meibum composition and quantity in meibomian gland dysfunction (MGD) result in tear film instability and dry eye. This exploratory study aimed to identify changes in (O-acyl)-ω-hydroxy fatty acid (OAHFA) and hydrocarbon chain (HC) unsaturation levels in meibum related to the presence and severity of MGD. <b><i>Methods:</i></b> Meibum samples were collected from 3 cohorts of adults with no MGD, mild-to-moderate MGD, and severe MGD in a noninterventional clinical trial (NCT01979887). OAHFAs, cholesterol esters (CE), HC unsaturation, and HC length in the meibum samples were quantified with ¹H-nuclear magnetic resonance spectroscopy using 2 methods of normalization. <b><i>Results:</i></b> Meibum samples from 62 subjects were analyzed: 21 non-MGD, 21 mild-to-moderate MGD, and 20 severe MGD. Meibum OAHFA and CE levels and HC unsaturation were reduced with increasing severity of MGD, with most pairwise comparisons significant (<i>P</i> < 0.05, <i>t</i>-tests), following the order non-MGD > mild-to-moderate MGD > severe MGD. Regardless of the resonances used for normalization, each pairwise comparison of OAHFA, CE, and HC unsaturation levels in MGD (combined severities) versus non-MGD samples was significant (<i>P</i> < 0.01, <i>t</i>-test). Analysis using various normalization equations showed reductions of 20%-22% for OAHFAs, 51%-57% for CE, and 36%-66% for HC unsaturation in MGD (combined severities) compared with non-MGD. HC length was not altered in MGD (combined severities) compared with non-MGD samples (<i>t</i>-test). <b><i>Conclusions:</i></b> Meibum OAHFA, CE, and HC unsaturation levels were reduced in MGD and were lowest in the severe MGD cohort. These findings may contribute to the understanding of the pathophysiology of MGD.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"562-570"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic Fibroblast Growth Factor Supports the Function of Limbal Niche Cells via the Wnt/β-Catenin Pathway.","authors":"Bihui Jin, Guanyu Su, Xiao Zhou, Lingjuan Xu, Wei Wang, Tianyu Zhou, Yongyao Tan, Shusheng Wang, Guigang Li","doi":"10.1089/jop.2024.0042","DOIUrl":"10.1089/jop.2024.0042","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To test the effects and underlying mechanisms of basic fibroblast growth factor (bFGF) on the limbal niche cell (LNC) function <i>ex vivo</i>. <b><i>Methods:</i></b> By using different concentrations of bFGF (0, 4, 8, 12, and 16 ng/mL) and fibroblast growth factor receptor (FGFR) inhibitors, the effects of bFGF on LNC proliferation, expression of stem cell markers, and transcription levels of the β-catenin were investigated. Single-cell RNA sequencing (scRNA-seq) was used to analyze the action and mechanisms of FGFR subtypes and the Wnt/β-catenin pathway during LNC culture. An mature corneal epithelial cell (MCEC)/LNC three-dimensional model was constructed to verify whether bFGF activates the Wnt/β-catenin pathway in LNC by inhibiting FGFR or β-catenin targets. <b><i>Results:</i></b> scRNA-seq showed that <i>FGFR1</i> is the main receptor in LNC, along with the molecules in the Wnt pathway, including <i>WNT2, FZD7, LRP5, LRP6,</i> and β-catenin. The 12 ng/mL bFGF treatment group showed higher LNC proliferation rate and transcription levels of <i>OCT4, SOX2, NANOG</i>, and β-catenin than any other groups (<i>P</i> < 0.001). In the MCEC/LNC co-culture model, MCEC/LNC treated with 12 ng/mL bFGF promoted the aggregation of the spheres than other groups, associated with increased transcription levels of <i>P63α</i>, <i>WNT2</i>, β-catenin, and a decreased transcription level of <i>CK12</i> (<i>P</i> < 0.001). Wnt/β-catenin inhibitor LF3 treatment reversed the abovementioned effect of bFGF. <b><i>Conclusions:</i></b> bFGF could maintain and promote the stemness of LNC via the <i>FGFR1</i>/<i>Wnt2</i>/<i>FZD7</i>/<i>LRP6</i> axis in a concentration-dependent manner.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"571-580"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}