Journal of Ocular Pharmacology and Therapeutics最新文献_第4页

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai. 超高海拔地区和海平面地区眼部麦粒肿的患病率和风险因素：日喀则和上海的横断面研究。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-04 DOI: 10.1089/jop.2024.0038

Chunren Meng, Qingquan Wei, Chufeng Gu, Shuai He, Chunyang Cai, Dongwei Lai, Qinghua Qiu

{"title":"Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.","authors":"Chunren Meng, Qingquan Wei, Chufeng Gu, Shuai He, Chunyang Cai, Dongwei Lai, Qinghua Qiu","doi":"10.1089/jop.2024.0038","DOIUrl":"10.1089/jop.2024.0038","url":null,"abstract":"Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"486-493"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534660","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

Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression: Implications for the Analysis of Cataract Development. 白内障不同发展阶段的眼内液代谢组差异：白内障发展分析的意义。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI: 10.1089/jop.2024.0067

Arturs Zemitis, Juris Vanags, Jingzhi Fan, Kristaps Klavins, Guna Laganovska

{"title":"Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression: Implications for the Analysis of Cataract Development.","authors":"Arturs Zemitis, Juris Vanags, Jingzhi Fan, Kristaps Klavins, Guna Laganovska","doi":"10.1089/jop.2024.0067","DOIUrl":"10.1089/jop.2024.0067","url":null,"abstract":"Introduction: The lens's metabolic demands are met through a continuous circulation of aqueous humor, encompassing a spectrum of components such as organic and inorganic ions, carbohydrates, glutathione, urea, amino acids, proteins, oxygen, carbon dioxide, and water. Metabolomics is a pivotal tool, offering an initial insight into the complexities of integrated metabolism. In this investigative study, we systematically scrutinize the composition of intraocular fluid in individuals afflicted with cataracts. Methods: The investigation involved a comprehensive analysis of aqueous humor samples from a cohort comprising 192 patients. These individuals were stratified by utilizing the SPONCS classification system, delineating distinct groups characterized by the hardness of cataracts. The analytical approach employed targeted quantitative metabolite analysis using HILIC-based liquid chromatography coupled with high-resolution mass spectrometric detection. The metabolomics data analysis was performed with MetaboAnalyst 5.0. Results: The results of the enrichment analysis have facilitated the inference that the discerned disparities among groups arise from disruptions in taurine and hypotaurine metabolism, variations in tryptophan metabolism, and modifications in mitochondrial beta-oxidation of short-chain saturated fatty acids and pyrimidine metabolism. Conclusion: A decline in taurine concentration precipitates diminished glutathione activity, prompting an elevated requirement for NAD+ and instigating tryptophan metabolism along the kynurenine pathway. Activation of this pathway is additionally prompted by interferon-gamma and UV radiation, leading to the induction of IDO. Concurrently, heightened mitochondrial beta-oxidation signifies a distinctive scenario in translocating fatty acids into the mitochondria, enhancing energy production.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"477-485"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559024","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

Ophthalmic Nanoemulsion Fingolimod Formulation for Topical Application. 用于局部应用的眼科纳米乳液芬戈莫德配方。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI: 10.1089/jop.2024.0055

Rama Kashikar, Samir Senapati, Narendar Dudhipala, Sandip K Basu, Nawajes Mandal, Soumyajit Majumdar

{"title":"Ophthalmic Nanoemulsion Fingolimod Formulation for Topical Application.","authors":"Rama Kashikar, Samir Senapati, Narendar Dudhipala, Sandip K Basu, Nawajes Mandal, Soumyajit Majumdar","doi":"10.1089/jop.2024.0055","DOIUrl":"10.1089/jop.2024.0055","url":null,"abstract":"Purpose: Fingolimod (FTY720; FT), a structural analog of sphingosine, has potential ocular applications. The goal of this study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. Methods: FT-NE formulations were prepared using homogenization followed by the probe sonication method. The lead FT-NE formulations (0.15% and 0.3% w/v loading), comprising soybean oil as oil and Tween® 80 and Poloxamer 188 as surfactants, were further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. Ocular bioavailability following topical application of FT-NE (0.3%) was examined in Sprague-Dawley rats. Results: The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature postfiltration through a polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release over 24 h, compared with the control FT solution (FT-S). In vivo studies revealed that effective concentrations of FT were achieved in the vitreous humor and retina following topical application of FT-NE. Conclusions: The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"504-512"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559025","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

A Prospective, Randomized, Controlled Clinical Investigation Comparing the Efficacy and Safety of Sodium Hyaluronate-Based Ophthalmical Viscosurgical Devices FIDIAL PLUS and IAL^®-F in Cataract Surgery. 一项前瞻性、随机对照临床研究，比较透明质酸钠眼科粘液手术器械 FIDIAL PLUS 和 IAL®-F 在白内障手术中的疗效和安全性。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-01 DOI: 10.1089/jop.2024.0044

Camilla Pagnacco, Roberto Tosi, Jessica Dalsaso, Sebastiano Fraccaroli, Filippo Saggin, Giorgio Marchini

{"title":"A Prospective, Randomized, Controlled Clinical Investigation Comparing the Efficacy and Safety of Sodium Hyaluronate-Based Ophthalmical Viscosurgical Devices FIDIAL PLUS and IAL®-F in Cataract Surgery.","authors":"Camilla Pagnacco, Roberto Tosi, Jessica Dalsaso, Sebastiano Fraccaroli, Filippo Saggin, Giorgio Marchini","doi":"10.1089/jop.2024.0044","DOIUrl":"10.1089/jop.2024.0044","url":null,"abstract":"Purpose: To protect the corneal endothelium, various ophthalmical viscoelastic devices (OVDs) are used during cataract surgery. In this study, we compared two sodium hyaluronate-based OVD, the bacteria-derived FIDIAL PLUS OVD (test) with the animal-derived IAL®-F OVD (reference) during the surgical procedure. Methods: Fifty patients with bilateral cataract participated in the study: 50 eyes randomly received FIDIAL PLUS and 50 eyes received IAL®-F (ratio 1:1). Noninferior efficacy of FIDIAL PLUS compared with reference OVD (first objective) was evaluated using a paired t-test comparing the mean percent loss of corneal endothelial cells (CECs) with FIDIAL PLUS against the mean percent loss with IAL®-F. Corneal endothelial protection during cataract surgery with FIDIAL PLUS without significant (≥30 mmHg) postoperative intraocular pressure (IOP) increase (main secondary objective) was assessed using a repeated measures logistic model comparing the incidence of significant postoperative IOP elevation between the two groups. Safety, tolerability, and efficacy were also evaluated by assessing secondary endpoints before and after surgery. Results: FIDIAL PLUS showed a statistically noninferior efficacy compared with IAL®-F; there was no significant increase in IOP in either group or different trends of the secondary endpoints were observed between the OVD groups. The safety profile was similar in both OVD groups and no adverse device effects were reported. Conclusions: This study demonstrates the equivalent efficacy, tolerability, and safety of the bacteria-derived FIDIAL PLUS compared with the animal-derived IAL®-F, confirming the clinical value of this product.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"469-476"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476838","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

Complement Factor B Inhibition or Deletion Is Not Sufficient to Prevent Neurodegeneration in a Murine Model of Glaucoma. 补体因子 B 的抑制或缺失不足以防止小鼠青光眼模型中的神经变性。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI: 10.1089/jop.2024.0046

Katie Dolan, Sha-Mei Liao, Maura Crowley, Chuanxi Xiang, Christopher M Adams, Ann Brown, Nhi Vo, Amy Chen, Omar Delgado, Natasha Buchanan, Chenying Guo, Ganesh Prasanna

{"title":"Complement Factor B Inhibition or Deletion Is Not Sufficient to Prevent Neurodegeneration in a Murine Model of Glaucoma.","authors":"Katie Dolan, Sha-Mei Liao, Maura Crowley, Chuanxi Xiang, Christopher M Adams, Ann Brown, Nhi Vo, Amy Chen, Omar Delgado, Natasha Buchanan, Chenying Guo, Ganesh Prasanna","doi":"10.1089/jop.2024.0046","DOIUrl":"10.1089/jop.2024.0046","url":null,"abstract":"Purpose: Activation of the classical complement pathway is thought to contribute to the development and progression of glaucoma. The role of alternative complement or amplification pathways in glaucoma is not well understood. We evaluated complement factor B (FB) expression in postmortem human ocular tissues with or without glaucoma and the effect of FB inhibition and deletion in a mouse ocular hypertensive model of glaucoma induced by photopolymerized hyaluronic acid glycidyl methacrylate (HAGM). Methods: Human CFB mRNA in human eyes was assessed by RNAscope and TaqMan. HAGM model was performed on C57BL6/J mice. The effect of FB in HAGM model was evaluated with an oral FB inhibitor and Cfb-/- mice. Complement mRNA and proteins in mouse eyes were assessed by TaqMan and western blot, respectively. Results: CFB mRNA in human glaucomatous macular neural retina and optic nerve head was upregulated. Cfb mRNA is also upregulated in the HAGM model. Oral FB inhibitor, ED-79-GX17, dosed daily at 200 mg/kg for 3 days after intraocular pressure (IOP) induction in wild-type mice showed complement inhibition in ocular tissues and significantly inhibited systemic complement levels. Daily dosing of ED-79-GX17 for 30 days or Cfb deletion was also unable to prevent retinal ganglion cell or axon loss 30 days after IOP induction in mice. Conclusion: The alternative complement component FB may not substantially contribute to RGC loss in the HAGM mouse glaucoma model despite upregulation of Cfb expression and activation of the alternative pathway. The relevance of these findings to human glaucoma remains to be determined.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"524-535"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559022","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

Review of Janus Kinase Inhibitors as Therapies for Noninfectious Uveitis. 作为非传染性葡萄膜炎疗法的 Janus 激酶抑制剂综述。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-24 DOI: 10.1089/jop.2024.0100

Hui Yu Juan, Shwu-Jiuan Sheu, De-Kuang Hwang

{"title":"Review of Janus Kinase Inhibitors as Therapies for Noninfectious Uveitis.","authors":"Hui Yu Juan, Shwu-Jiuan Sheu, De-Kuang Hwang","doi":"10.1089/jop.2024.0100","DOIUrl":"https://doi.org/10.1089/jop.2024.0100","url":null,"abstract":"Uveitis remains one of the leading causes of blindness worldwide, with different etiologies requiring separate approaches to treatment. For over a decade, oral, topical, and local injection of corticosteroids as well as systemic conventional disease-modifying antirheumatic drugs (DMARDs) have remained the most effective treatment for noninfectious uveitis (NIU). Systemic administration of antitumor necrosis factor-α and other biological DMARDs have been used for treating cases that responded inadequately to conventional treatments. Unfortunately, some refractory patients still suffer from frequent attacks despite the combination of multiple treatments. Recently, there has been promising evidence for Janus kinase (JAK) inhibitors as the next-generation therapy for NIU. The JAK/signal transducers and activators of the transcription (STAT) signaling pathway mediate the downstream events involved in immune fitness, tissue repair, inflammation, apoptosis, and adipogenesis by binding various ligands, such as cytokines, growth hormones, and growth factors. The mutation or loss of JAK/STAT components is implicated in autoimmune diseases, thus inhibition of such pathways has been an important area of research in therapeutic development.1 In this review, we provide a comprehensive overview of the efficacy and safety of JAK inhibitors for the management of NIU, with evidence from current trials and case reports.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307971","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

Nanotechnology in Ocular Drug Delivery: The Potential of Polymeric Micelles as a Drug Delivery Vehicle. 纳米技术在眼部给药中的应用：聚合物胶束作为给药载体的潜力。

IF 2.3 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-12 DOI: 10.1089/jop.2024.0060

Mehul Luhar,Ravi Viradiya,Sanjay Panjabi,Gayatri Patel

引用次数: 0

Role of NADPH Oxidase 4 on Dry Eye Syndrome in Mice. NADPH 氧化酶 4 对小鼠干眼症的作用

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-04-26 DOI: 10.1089/jop.2024.0002

Mian Guo, Taixiang Liu, Yuan Miao, Xiaoli Pan, Bo Liu

{"title":"Role of NADPH Oxidase 4 on Dry Eye Syndrome in Mice.","authors":"Mian Guo, Taixiang Liu, Yuan Miao, Xiaoli Pan, Bo Liu","doi":"10.1089/jop.2024.0002","DOIUrl":"10.1089/jop.2024.0002","url":null,"abstract":"Objective: This study aims to investigate the effect of NADPH oxidase 4 (NOX4)-mediated inflammation on concanavalin A (ConA)-induced dry eye syndrome (DES) in mice. Methods: Thirty-six mice were randomly divided into Control, Model, no-load Control, and NOX4 interference group. Adenovirus was injected (10 μL) into the lacrimal glands of both eyes of mice in no-load Control group and NOX4 interference group. Four days after adenovirus injection, the Control group was injected with phosphate-buffered saline, and the other groups were injected with ConA (200 μg) in the lacrimal glands of mice to establish DES models. The tear secretion rate was estimated by phenol red thread test. Lissamine green eye staining was used to evaluate conjunctival damage. The corneal surface was observed by hematoxylin-eosin (HE) staining and scanning electron microscopy (SEM). The morphology and quantity of conjunctival epithelial cells and goblet cells were observed by Periodic acid-Schiff staining. The expression of NOX4, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), interleukin-1β (IL-1β), and mucin 5 subtype AC (MUC5AC) was detected by immunohistochemistry. Results: Compared with the Control group, the Model group showed a significant decrease in tear secretion and an upregulation in microscopic image score. The HE staining and SEM showed corneal and conjunctiva damage in the Model group. The protein expression of NOX4, NLRP3, and IL-1β was upregulated, but MUC5AC was downregulated in the Model group. After interfering with NOX4, all these indicators were reversed. Conclusion: The pathological process of concanavalin A-induced DES appears to be related to NOX4.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"452-458"},"PeriodicalIF":1.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864364","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

Evaluation of Dose-Response Relationship in Novel Extended Release of Targeted Nucleic Acid Nanocarriers to Treat Secondary Cataracts. 评估新型缓释靶向核酸纳米载体治疗继发性白内障的剂量-反应关系

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-06-20 DOI: 10.1089/jop.2024.0024

Camila Vardar, Mindy George-Weinstein, Robert Getts, Mark E Byrne

{"title":"Evaluation of Dose-Response Relationship in Novel Extended Release of Targeted Nucleic Acid Nanocarriers to Treat Secondary Cataracts.","authors":"Camila Vardar, Mindy George-Weinstein, Robert Getts, Mark E Byrne","doi":"10.1089/jop.2024.0024","DOIUrl":"10.1089/jop.2024.0024","url":null,"abstract":"Purpose: The present study aimed to determine the dose-response relationship between targeted nanocarriers released from a novel, sustained release formulation and their ability to specifically deplete cells responsible for the development of posterior capsular opacification (PCO) in month-long, dynamic cell cultures. Methods: Injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) triblock copolymer hydrogels were loaded with either a low or a high dose of doxorubicin-loaded antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: A lower dose of nanocarriers in hydrogel depleted BAI1+ cells at a slower rate than the higher dose, whereas both reached over 90% BAI1+ cellular nonviability at 28 days. Both treatment groups also significantly lowered the relative abundance of BAI1+ cells in the population compared with the control group. Conclusions: Controlled release of a lower dose of nanocarriers can still achieve therapeutically relevant effects in the prevention of PCO, while avoiding potential secondary effects associated with the administration of a higher dose.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"459-466"},"PeriodicalIF":1.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427044","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

PLL-g-PEG Polymer Inhibits Antibody-Drug Conjugate Uptake into Human Corneal Epithelial Cells In Vitro. PLL-g-PEG 聚合物抑制人角膜上皮细胞体外吸收抗体-药物共轭物

IF 16.4 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-06-27 DOI: 10.1089/jop.2024.0019

David Kleinman, Sana Iqbal, Anita K Ghosh, Sean D Ogle, Simon Kaja, Mark Mitchnick, Jenni J Hakkarainen

{"title":"PLL-g-PEG Polymer Inhibits Antibody-Drug Conjugate Uptake into Human Corneal Epithelial Cells In Vitro.","authors":"David Kleinman, Sana Iqbal, Anita K Ghosh, Sean D Ogle, Simon Kaja, Mark Mitchnick, Jenni J Hakkarainen","doi":"10.1089/jop.2024.0019","DOIUrl":"10.1089/jop.2024.0019","url":null,"abstract":"Purpose: Antibody-drug conjugates (ADCs) are a relatively recent advance in the delivery of chemotherapeutics that improve targeting of cytotoxic agents. However, despite their antitumor activity, severe ocular adverse effects, including vision loss, have been reported for several ADCs. The nonspecific uptake of ADCs into human corneal epithelial cells (HCECs) and their precursors via macropinocytosis has been proposed to be the primary mechanism of ocular toxicity. In this study, we evaluated the ability of a novel polymer, poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), to decrease the ADC rituximab-mc monomethylauristatin F (MMAF) (RIX) uptake into human corneal epithelial (HCE-T) cells. Methods: HCE-T cells were exposed to increasing concentrations of RIX to determine inhibition of cell proliferation. HCE-T cells were treated with PLL-g-PEG, the macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA), or vehicle. After 30 min of incubation, RIX was added. ADC was detected by fluorescent anti-human immunoglobulin G and fluorescently conjugated dextran as viewed by microscopy. Results: RIX caused dose-dependent inhibition of HCE-T cell proliferation. EIPA significantly reduced RIX uptake and decreased macropinocytosis as assessed by direct quantification of RIX using a fluorescently conjugated anti-human antibody as well as quantification of macropinocytosis using fluorescently conjugated dextran. PLL-g-PEG resulted in a dose-dependent inhibition of RIX uptake with half-maximal inhibitory concentrations of 0.022%-0.023% PLL-g-PEG. Conclusion: The data show PLL-g-PEG to be a potent inhibitor of RIX uptake by corneal epithelial cells and support its use as a novel therapeutic approach for the prevention of ocular adverse events associated with ADC therapy.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"419-427"},"PeriodicalIF":16.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468823","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