Journal of Ocular Pharmacology and Therapeutics最新文献

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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. 源自脂肪间充质干细胞的细胞外囊泡通过激活 Nrf2 信号通路缓解视网膜色素上皮细胞的凋亡和氧化应激
IF 1.9 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1089/jop.2024.0064
Jin Sun Hwang, Hyun Beom Song, Geonhui Lee, Sangmoo Jeong, Dae Joong Ma
{"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 (H<sub>2</sub>O<sub>2</sub>) 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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}
引用次数: 0
Inflammation in Dry Eye Disease-Pathogenesis, Preclinical Animal Models, and Treatments. 干眼症中的炎症--发病机制、临床前动物模型和治疗方法。
IF 1.9 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI: 10.1089/jop.2024.0103
Santosh Bhujbal, Ilva D Rupenthal, Philipp Steven, Priyanka Agarwal
{"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}
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
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
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 1.9 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":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}
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 1.9 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":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}
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
Long-Term Stability, Sterility, And Cost-Effectiveness of 0.05% Chlorhexidine Gluconate as Antisepsis for Intravitreal Injection. 0.05% 洗必泰葡萄糖酸盐作为玻璃体内注射防腐剂的长期稳定性、无菌性和成本效益。
IF 16.4 4区 医学
Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI: 10.1089/jop.2024.0071
Asad F Durrani, Bita Momenaei, Viren Soni, Matthew Tennant, Jason Hsu, James Vander, Marc Spirn, Eugene Yu-Chuan Kang, Yih-Shiou Hwang, Gagan Kaushal, Sunir J Garg
{"title":"Long-Term Stability, Sterility, And Cost-Effectiveness of 0.05% Chlorhexidine Gluconate as Antisepsis for Intravitreal Injection.","authors":"Asad F Durrani, Bita Momenaei, Viren Soni, Matthew Tennant, Jason Hsu, James Vander, Marc Spirn, Eugene Yu-Chuan Kang, Yih-Shiou Hwang, Gagan Kaushal, Sunir J Garg","doi":"10.1089/jop.2024.0071","DOIUrl":"10.1089/jop.2024.0071","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Commercially available chlorhexidine gluconate (CHG) has a beyond-use date of 24 h. This study evaluated the stability and sterility of 0.05% CHG for 30 days after opening and compared its cost to povidone iodine (PI) for intravitreal injection antisepsis. <b><i>Methods:</i></b> 0.05% CHG was aliquoted into 1-mL syringes and stored at room temperature or refrigerated. Turbidity, pH, high-performance liquid chromatography (HPLC), and sterility testing were performed. A cost analysis was conducted. <b><i>Results:</i></b> 0.05% CHG remained stable for at least 30 days. All samples had measured turbidity <0.5 nephelometric turbidity units. The pH of all samples remained between 5.0 and 7.0. HPLC demonstrated CHG concentration at day 30 relative to day 0 of 98.52% ± 4.16% at room temperature and 99.99% ± 3.38% at 2°C -6°C. The cost per week to perform 150 injections using 0.05% CHG was $463.25 when opening a new bottle daily compared with $16.73 for 5% PI. This cost decreased to $23.16 when utilizing a bottle of CHG for 30 days. <b><i>Conclusion:</i></b> 0.05% CHG remains stable and sterile for at least 30 days after opening. The ability to use CHG for at least 30 days after its opening significantly decreases its utilization expense.</p>","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"581-587"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017841","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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