Journal of Ocular Pharmacology and Therapeutics最新文献

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Duration of Bare Sclera Pterygium Surgery Combined with Mitomycin C with and Without Tranexamic Acid: A Randomized Double-Blind Controlled Trial. 裸巩膜翼状胬肉手术联合使用丝裂霉素 C 和不使用氨甲环酸的持续时间:随机双盲对照试验。
IF 1.9 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-20 DOI: 10.1089/jop.2024.0068
Nevo Kovalis, Shmuel Graffi, Shadi Safuri, Yinon Shapira, Geulah Ben-David, Michael Mimouni
{"title":"Duration of Bare Sclera Pterygium Surgery Combined with Mitomycin C with and Without Tranexamic Acid: A Randomized Double-Blind Controlled Trial.","authors":"Nevo Kovalis, Shmuel Graffi, Shadi Safuri, Yinon Shapira, Geulah Ben-David, Michael Mimouni","doi":"10.1089/jop.2024.0068","DOIUrl":"https://doi.org/10.1089/jop.2024.0068","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To evaluate the efficacy of subconjunctival tranexamic acid (TXA) in reducing intraoperative bleeding, shortening surgery duration, and improving postoperative outcomes in pterygium surgery. <b><i>Methods:</i></b> In this double-blind, randomized controlled trial, 50 eyes of 50 patients undergoing pterygium surgery were randomly assigned to receive either subconjunctival injection of 0.25 mL of 5% TXA (TXA group, <i>n</i> = 25) or an equivalent volume of saline (control group, <i>n</i> = 25). Baseline characteristics, including age, gender, working environment, allergies, preoperative logMAR best-corrected visual acuity, and systemic anticoagulant or antiplatelet therapy, were similar between the groups. The primary outcome measures were intraoperative bleeding, surgery duration, and the number of eye spears used. Secondary outcome measures included postoperative visual acuity and pterygium recurrence rates at 3 years post-surgery. <b><i>Results:</i></b> No significant differences were observed between the TXA group and the control group in terms of surgery duration (445.3 ± 94.8 s vs. 423.5 ± 80.6 s, <i>P</i> = 0.40), the number of eye spears used (3.5 ± 2.4 vs. 3.5 ± 2.6, <i>P</i> = 0.97), or the weight of absorbed blood (1.94 ± 1.40 grams vs. 1.90 ± 1.25 grams, <i>P</i> = 0.91). Additionally, there were no significant differences in postoperative visual acuity (0.14 ± 0.13 logMAR vs. 0.20 ± 0.19 logMAR, P = 0.39) or pterygium recurrence rates at 3 years post-surgery (8.0% vs. 4.4%, <i>P</i> = 0.60). Subconjunctival TXA injection was safe, with no reported adverse events or complications associated with its use. <b><i>Conclusion:</i></b> Subconjunctival injection of TXA did not significantly reduce intraoperative bleeding, shorten surgery duration, or improve postoperative outcomes in pterygium surgery. The intervention was safe and well-tolerated, but further research is warranted to explore alternative interventions or modifications to the surgical technique that may improve outcomes in pterygium surgery.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676107","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}
引用次数: 0
Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension. 用于治疗青光眼和眼压过高的新型无防腐剂比马前列素 0.01% 眼科凝胶的临床前和临床药代动力学。
IF 1.9 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-07 DOI: 10.1089/jop.2024.0092
Carl Erb, Fotis Topouzis, Hari Jayaram, Fanny Allan, Sylvie Nisslé, Francisco J Muñoz-Negrete, Ingeborg Stalmans
{"title":"Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension.","authors":"Carl Erb, Fotis Topouzis, Hari Jayaram, Fanny Allan, Sylvie Nisslé, Francisco J Muñoz-Negrete, Ingeborg Stalmans","doi":"10.1089/jop.2024.0092","DOIUrl":"https://doi.org/10.1089/jop.2024.0092","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Pharmacokinetic evaluation of ocular penetration and systemic accumulation of preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel). <b><i>Methods:</i></b> In a preclinical study, pigmented rabbits received a single ocular administration of PFB 0.01% gel (<i>N</i> = 15) or preserved bimatoprost 0.01% or 0.03% ophthalmic solution [PB 0.01% (<i>N</i> = 15) or PB 0.03% (<i>N</i> = 15)]. The aqueous humor, iris, and ciliary body were analyzed for bimatoprost+bimatoprost free acid. In a Phase 1, randomized, open-label clinical study, healthy participants received PFB 0.01% gel (<i>N</i> = 20) or PB 0.01% (<i>N</i> = 20) daily in each eye (Days 1-15). Bimatoprost levels in human plasma were analyzed on Days 1 and 15. All serological analyses used validated methods. Adverse events were collected throughout and ocular assessments were performed on Days 1 and 15. <b><i>Results:</i></b> In the preclinical study, Cmax (bimatoprost+bimatoprost free acid) for PFB 0.01% gel, PB 0.01%, and PB 0.03% was 50.2, 26.3, and 59.9 ng/mL; AUC<sub>0.5-8 h</sub> was 134.0 ng·h/mL, 67.0 ng·h/mL, and 148.0 ng·h/mL. In the clinical study, systemic exposure to bimatoprost (AUC<sub>0-last</sub>) on Days 1 and 15 was lower for PFB 0.01% gel (0.5248 and 0.5645 ng·min/mL) than PB 0.01% (0.8461 and 0.7551 ng·min/mL), with no systemic accumulation of bimatoprost in either group. There were no clinically important differences between groups in ocular or systemic tolerability in the clinical study and no serious adverse events. <b><i>Conclusions:</i></b> PFB 0.01% gel showed improved ocular penetration compared with PB 0.01%. Systemic absorption was comparable, with a favorable clinical safety profile, supporting PFB 0.01% gel as a potential treatment for glaucoma and ocular hypertension.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605046","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}
引用次数: 0
Eyes on New Product Development. 关注新产品开发。
IF 1.9 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-06 DOI: 10.1089/jop.2024.0170
Gary D Novack
{"title":"Eyes on New Product Development.","authors":"Gary D Novack","doi":"10.1089/jop.2024.0170","DOIUrl":"https://doi.org/10.1089/jop.2024.0170","url":null,"abstract":"","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590667","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}
引用次数: 0
Effects of Intense Pulsed Light on Presumed Neuropathic Pain Associated with Meibomian Gland Dysfunction: A Before-After Study. 强脉冲光对与睑板腺功能障碍有关的假定神经性疼痛的影响:前后对比研究
IF 1.9 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-06 DOI: 10.1089/jop.2024.0099
Gautier Hoarau, Anne-Laurence Best, Sourour Zina-Meziou, Maya Benali-Abdallah, Mhamed Loukil, Magalie Bouvet, Emmanuel Barreau, Antoine Rousseau, Marc Labetoulle
{"title":"Effects of Intense Pulsed Light on Presumed Neuropathic Pain Associated with Meibomian Gland Dysfunction: A Before-After Study.","authors":"Gautier Hoarau, Anne-Laurence Best, Sourour Zina-Meziou, Maya Benali-Abdallah, Mhamed Loukil, Magalie Bouvet, Emmanuel Barreau, Antoine Rousseau, Marc Labetoulle","doi":"10.1089/jop.2024.0099","DOIUrl":"https://doi.org/10.1089/jop.2024.0099","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Meibomian gland dysfunction (MGD) may cause chronic ocular surface pain (COSP) with a neuropathic component that can significantly impact quality of life and be poorly responsive to conventional treatments of MGD. Intense pulsed light (IPL) is an emerging treatment already acknowledged as improving refractory MGD, potentially modulating inflammatory mediators on the ocular surface. This study aimed to assess the impact of IPL on COSP associated with unresponsive MGD. <b><i>Methods:</i></b> A monocentric prospective study has been conducted from 2021 to 2023 on patients presenting with moderate MGD and COSP non-responsive to conventional treatments of MGD. Neuropathic pain components were suspected when severe discomfort (OSDI score above 33/100) was observed despite moderate objective signs. Three sessions of IPL were performed at a two-week interval. The primary outcome was change in OSDI at day 60. Secondary outcomes included OSDI modification at D120, DEQ-5, and Pentascore results at D60/D120, together with changes in clinical [Schirmer I, Fluorescein Break-up time (BUT), fluorescein staining, and MGD classification] and paraclinical tests [noninvasive BUT, tear meniscus height (TMH), and meibography]. <b><i>Results:</i></b> A significant improvement of COSP (<i>p</i> < 0.05 for changes in OSDI and Pentascore results) was observed 2 and 4 months after the last IPL session, together with an improvement in tear film stability, corneal epitheliopathy, meibomian gland obstruction, and TMH. <b><i>Conclusion:</i></b> The results of this study suggest the beneficial effect of IPL on neuropathic component of COSP associated with MGD. The underlying mechanisms involved in that improvement, presumably related to downgrading of inflammatory effectors, remain however to be explored.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583354","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}
引用次数: 0
Eyes on New Product Development. 关注新产品开发。
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-09-26 DOI: 10.1089/jop.2024.0155
Gary D Novack
{"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}
引用次数: 0
Neuritin 1 Drives Therapeutic Preservation of Retinal Ganglion Cells in an Ex Vivo Human Glaucoma Model. Neuritin 1 在体外人类青光眼模型中驱动视网膜神经节细胞的治疗性保存。
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-07-12 DOI: 10.1089/jop.2024.0041
Shahna S Hameed, Nicole E Bodi, Ryan C Miller, Tasneem P Sharma
{"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":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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. 不含防腐剂的拉坦前列素阳离子乳剂对开角型青光眼和并发眼表疾病患者的疗效和安全性:随机 2 期研究。
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI: 10.1089/jop.2024.0029
Jason Bacharach, Eugene B McLaurin, Steven Silverstein, Mourad Amrane, Jean-Sebastien Garrigue, Dahlia Ismail, William J Flynn
{"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":16.4,"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}
引用次数: 0
Comparative Ocular Pharmacokinetics of Dexamethasone Implants in Rabbits. 地塞米松植入物在兔子眼部的药代动力学比较。
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-07-24 DOI: 10.1089/jop.2024.0052
Jihyun Won, Juhyung Kang, Wonku Kang
{"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<sup>®</sup>, which is currentlyused in the market. <b><i>Methods:</i></b> Ozurdex<sup>®</sup> 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<sup>®</sup>. The overall patterns of the cumulative release of both implants are similar. <b><i>Conclusions:</i></b> NDF-SI01 could alternate Ozurdex<sup>®</sup> 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}
引用次数: 0
Basic Fibroblast Growth Factor Supports the Function of Limbal Niche Cells via the Wnt/β-Catenin Pathway. 碱性成纤维细胞生长因子通过 Wnt/β-Catenin 通路支持边缘壁龛细胞的功能
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-07-31 DOI: 10.1089/jop.2024.0042
Bihui Jin, Guanyu Su, Xiao Zhou, Lingjuan Xu, Wei Wang, Tianyu Zhou, Yongyao Tan, Shusheng Wang, Guigang Li
{"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}
引用次数: 0
Changes in Human Meibum Lipid Composition Related to the Presence and Severity of Meibomian Gland Dysfunction. 与睑板腺功能障碍的存在和严重程度有关的人类睑板腺脂质成分的变化
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI: 10.1089/jop.2024.0063
Ashley Nguyen, Kugen K Naidoo, Layla Ajouz, Xiaoming Xu, Cathy Zhao, Michael R Robinson, Douglas Borchman
{"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 <sup>1</sup>H-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":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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