- 首页
- 产品推荐个人精选服务科研辅助服务教育大数据服务行业精选服务学科系列服务产品服务
- 期刊大全
- 充值
- 会员
- 职称材料
- 首页
- 产品服务
- 知识脉络
- 期刊大全
- 充值
- 会员
- 职称材料
智能检索
二次检索
任意字段
在结果中检索
在结果中去除
暂无数据
共
35
条结果 ，以下是1
-
20条
1 / 2
已选:0 清除
批量下载
批量引用
相关度
摘要： 利非斯特(lifitegrast)由爱尔兰夏尔开发公司(Shire Dev Llc)研发,是新型的小分子整合素(integrin)抑制药,能拮抗淋巴细胞功能相关抗原-1(LFA-1),阻断与其同源配体细胞间黏附分子-1(ICAM-1)的相互作用。干扰引起干眼病的角膜与结膜组织的ICAM-1过度表达。2015年4月9日向美国食品药品管理局(FDA)提出新药申请,并获得优先审查资格。在补充临床试验的有效性和安全性数据后,于2016年7月11日获得FDA批准上市,是首个治疗干眼症症状和体征的药物。商品名为Xiidra~。该文对利非斯特的非临床和临床药理毒理学、临床研究、适应证、剂量与用法、用药注意事项、不良反应及知识产权状态和国内外研究进展等进行介绍。
关键词: 利非斯特 ；干眼症 ；整合素抑制药
被引量
1
摘要： 近日，美国食品药品管理局（FDA）批准lifitegrast滴眼液（Xiidra）为首个可用于干眼症治疗的新型淋巴细胞功能相关抗原拮抗剂类药物。
干眼症伴有一系列症状包括泪液减少或泪液量异常等，其发病率与年龄增长呈正相关，在30～40岁的成年人群中该病的发病率约为5％，在65岁以上的老年人群中发病率为10％～15％，好发于女性。如病情严重或未及时接受治疗，干眼症可导致角膜疼痛和角膜炎，严重影响患者的日常生活，降低患者眼睛对干燥环境的耐受性。
关键词: 干眼症 ；FDA批准 ；治疗 ；淋巴细胞功能相关抗原 ；美国食品药品管理局 ；发病率 ；成年人群 ；老年人群
【期刊论文】 • Li, Jing-Xing 1,2,3Tsai, Yi-Yu 2,4,5Lai, Chun-Ting 4,6Li, You-Ling 2,4
+2位作者
• JOURNAL OF CLINICAL MEDICINE • Volume 11
(17)，
2022 ，pp. 5014
- 5014
摘要： Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin antagonist, was approved in the United States in July 2016 as a 5% (50 mg/mL) ophthalmic solution for DED management. Currently, no meta-analysis and systemic review based on relevant studies have been conducted. This study aimed to evaluate the efficacy and safety of lifitegrast in patients with DED. We systematically searched Embase, Medline, PubMed, and Web of Science for randomized controlled trials (RCTs) and nonrandomized studies evaluating lifitegrast effects on symptomatic DED. Then, inferior corneal staining score, total corneal staining score (TCSS), nasal lissamine staining score (NLSS), total lissamine staining score, ocular discomfort score (ODS), eye discomfort score (visual analog scale (VAS) score), eye dryness score (EDS), ocular surface disease index score (OSDI-S), and tear break-up time (TBUT) were assessed. Clinical global impression and safety profiles were also evaluated. The studies were pooled in a random-effects model. We included five RCTs, one case-control study, and four longitudinal or retrospective studies, comprising 3197 participants. In the meta-analysis, lifitegrast was superior to the placebo because it improved TCSS, NLSS, TBUT, ODS, eye discomfort score, EDS, and OSDI-Sin DED. However, lifitegrast showed higher risks for ocular and non-ocular treatment-emergent adverse events (TEAEs) overall or at a mild or moderate level. Nonetheless, its incidence of adverse events slightly differed from that in the placebo, especially instillation site discomforts and dysgeusia, thereby considered safe and tolerable. Claims of withdrawal during follow-up caused by TEAEs were extremely rare. Lifitegrast improves DED, although dysgeusia, installation site pain, and irritation may be a concern for some. Overall, most of the adverse events are tolerable. Lifitegrast can alleviate refractory DED and improves patients' quality of life.
关键词: dry eye disease ；DED ；lifitegrast ；lymphocyte function-associated antigen 1 ；LFA-1 ；Xiidra
被引量
31
【期刊论文】 • Ferrete, T. 1
摘要： Graft-versus-host disease (GVHD) is a common complication in patients undergoing allogeneic stem cell transplantation for acute myeloblastic leukemia that could be very difficult to treat. Lifitegrast 5% (Xiidra (R), Novartis), a new immunosuppressive eye drop, was recently approved by the FDA for the treatment of severe dry eye and is currently under review by the European Medicines Agency. In France, lifitegrast has been approved by the French authorities for temporary use in refractory dry eye syndrome resistant to tear substitutes and topical cyclosporine. To date, serious complications have been reported only exceptionally. In this article, we report the case of a 65-year-old patient with a medical history of acute myeloid leukemia (AML) diagnosed in 2015 who received a first matched related donor transplant. In 2019, this patient developed chronic GVH involving the skin, oral mucosa and eye. Despite taking topical and systemic medications for 3 months, the patient did not report relief of ocular symptoms. Therefore, lifitegrast was prescribed. To our knowledge, we report the first case of corneal perforation in which evisceration was required following treatment with topical lifitegrast for chronic GVH. In the case presented here, it can be assumed that the underlying mechanisms leading to corneal perforation are multifactorial. Using drug accountability criteria, lifitegrast appears to be strongly associated with the development of bacterial keratitis and corneal perforation. (C) 2021 Elsevier Masson SAS. All rights reserved.
关键词: Lifitegrast ；Dry eye ；Infectious keratitis ；Eye perforation ；Evisceration
被引量
8
【期刊论文】 • • The Medical letter on drugs and therapeutics SCIE
• Volume 67
(1737)，
2025 ，pp. 145
- 146
关键词: Cequa ；Eysuvis ；Miebo ；Optilight ；Restasis ；Tryptyr ；Tyrvaya ；Veyve ；Xiidra ；acoltremon ；adverse effects ；dosage ；dry eye disease ；efficacy ；eye ；lactation ；lifitegrast ；loteprednol ；ophthalmic cyclosporine ；perfluorohexyloctane ；pregnancy ；safety ；varenicline
【期刊论文】 • Navre, Aayushi Ashish 1Sudhakar, Yogeswari 1,2Kumar, Manthani Shiva 1Dalsaniya, Sagar Chandrakant 1,2
+5位作者
• Organic Process Research & Development SCIE
PubMed
CA
EI
• Volume 29
(7)，
2025 ，pp. 1694
- 1702
摘要： A scalable enzymatic process has been developed for the preparation of optically pure 3-bromo- or 3-methylsulfonyl-substituted l-phenylalanine (S)-1a-b, which serves as key intermediates in the synthesis of lifitegrast. This method utilizes enzymatic dynamic kinetic resolution (DKR) of the ethyl esters of racemic 3-bromo- or 3-methylsulfonyl-substituted dl-phenylalanine esters (rac-8a-b), catalyzed by the commercially available protease enzyme Alcalase. The reaction was carried out in a miniemulsion system that acts as a nanoreactor with high substrate loading (50% w/v). Notably, the process was completed within 24 h using less than 10% (w/w) of the enzyme. The desired optically pure (S)-isomer was obtained with >90% isolated yield and >99% enantiomeric excess (e.e.) under these conditions. Furthermore, the solvent system, along with the surfactant and enzyme, was successfully recycled, highlighting the sustainability and cost-efficiency of the process.
关键词: lifitegrast ；miniemulsion ；nanoreactor ；DKR ；protease ；process development
关键词: Cequa ；Eysuvis ；Miebo ；Optilight ；Restasis ；Tyrvaya ；Vevye ；Xiidra ；adverse effects ；dosage ；dry eye disease ；eye ；lifitegrast ；loteprednol ；ophthalmic cyclosporine ；opthalmic cyclosporine ；perfluorohexyloctane ；safety ；varenicline
被引量
1
【期刊论文】 • Patil, Sunanda 1,2Sawale, Gayatri 1Ghuge, Santosh 1Sathaye, Sadhana 1
摘要： Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS (R) [cyclosporine 0.05% ophthalmic emulsion], VEVYE (R) [cyclosporine 0.1% ophthalmic solution], and CEQUA (TM) [cyclosporine 0.09% ophthalmic solution]), XIIDRA (R) (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS (TM) (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO (TM) (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA (TM) (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight (TM) (intense pulsed light [IPL] device), TearCare (R) system, and TearScience (TM) LipiFlow (TM) thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS (R) and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE (R) (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial;there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. What is known center dot Dry eye disease is a multifactorial ocular surface disease that affects 5-50% of the population.center dot The information about previous, current, and upcoming treatment options for dry eye disease is scattered in different publications.What is new center dot This narrative review provides a comprehensive overview of currently approved and upcoming treatment options for dry eye disease in a nutshell.center dot Similar to the existing approved treatments, upcoming treatments are targeted at reducing inflammation and blocking the inflammatory cytokines.center dot Based on its success in treating dry eye disease, cyclosporine remains a major focus in upcoming treatments with changes in formulations.
关键词: Dry eye disease ；Keratoconjunctivitis sicca ；Approved treatment options for dry eye disease ；Upcoming treatments for dry eye disease
被引量
9
【期刊论文】 • Girkar, Arvind Noronha, Dujon Patil, Prashant B. Mandewale, Mustapha
+3位作者
• Organic Process Research & Development 中科院3区
JCR:Q1
JCR:Q2
• Volume 28
(12)，
2024 ，pp. 4374
- 4379
摘要： A straightforward, efficient, and scalable commercial manufacturing process was developed for the ophthalmic anti-inflammatory drug lifitegrast via a novel ester intermediate from commercially available starting materials. Lifitegrast (Xiidra) was approved by the FDA on July 11, 2016, for the treatment of signs and symptoms of dry eye, a syndrome called keratoconjunctivitis sicca. The breakthrough step of this new process is the discovery of an N-Boc deprotection reaction that simultaneously transesterifies an intermediate to a new ester by using oxalyl chloride, which has favorable isolation properties. As a result of transesterification, the hydrolysis of the new ester intermediate occurs under milder conditions, which improves the quality of the product by reducing racemization. Lifitegrast prepared from this new process complied with the quality guidelines, as per the International Council for Harmonization (ICH). By using this new process, lifitegrast was produced on a 2 kg scale with an overall yield of 66%.
关键词: lifitegrast ；transesterification ；N-Boc deprotection ；novel process ；ICH
被引量
1
【期刊论文】 • Kaduk, James A. 1,2
摘要： A proposed crystal structure of lifitegrast Form A has been derived using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Lifitegrast sesquihydrate Form A crystallizes in space group P2(1) (#4) with a = 18.2526(4), b = 5.15219(6), c = 30.1962(6) & Aring;, beta = 90.8670(19), V = 2839.35(7) & Aring;(3), and Z = 4 at 295 K. The crystal structure consists of discrete lifitegrast molecules linked by hydrogen bonds among carboxylic acid groups, carbonyl groups, and water molecules into a three-dimensional framework. The water molecules occur in clusters. Each water molecule acts as a donor in two O-H & ctdot;O hydrogen bonds, and as an acceptor. One water molecule acts as an acceptor in a water-water O-H & ctdot;O hydrogen bond, and all three water molecules are acceptors in C-H & ctdot;O hydrogen bonds. Each carboxylic acid group acts as a donor in a strong discrete O-H & ctdot;O hydrogen bond;one to a water molecule and the other to a carbonyl group. The amino groups both form N-H & ctdot;O hydrogen bonds to carbonyl groups. The powder pattern has been submitted to ICDD (R) for inclusion in the Powder Diffraction File (TM) (PDF (R)).
关键词: lifitegrast ；Xiidra ；crystal structure ；Rietveld refinement ；density functional theory
【期刊论文】 • Wu, Chuanjun 1Guo, Heng 1Tang, Jiawei 1Xia, Lintao 1
+8位作者
• Organic Process Research & Development 中科院3区
JCR:Q1
JCR:Q2
• Volume 28
(3)，
2024 ，pp. 693
- 703
摘要： In the present study, a practical chemoenzymatic method was developed for the synthesis of chiral phenylalanine derivative 1, which is the key intermediate of Lifitegrast. In this established process, a simple and effective Zn/HCl reduction system was employed to obtain N-acetyl-3-bromo-phenylalanine 6, which served as the substrate for the subsequent enzymatic resolution process. Then, the key chiral intermediate, 3-bromo-l-phenylalanine 7, could be obtained using acylase (ACY) AmACY. Upon process optimization, the chemical reaction was executed at a 300 g scale, with a notable substrate concentration reaching up to 100 g/L. The process achieved a yield of 40%, compared to a maximum theoretical yield of 50%, and exhibited an enantiomeric excess (ee) value reaching up to 99.9%. A simple and effective Zn/HCl reduction system was employed to obtain N-acetyl-3-bromo-phenylalanine 6, which served as the substrate for the subsequent enzymatic resolution process. This synthetic pathway was effectively executed, yielding 1 center dot HCl with a purity of 99.7% and an ee value of 99.9%, culminating in an overall yield of 23.4%. Additionally, the undesired ( D )-6 enantiomer was recycled to form ( rac )-6, employing an acetanhydride/acetic acid (Ac2O/AcOH) system. This recycling process achieved a yield of 47.5%, relative to a maximum theoretical yield of 50%, and a purity level of 99.8%.
关键词: Lifitegrast ；enzymatic resolution ；phenylalaninederivatives ；synthesis process
被引量
1
【期刊论文】 • • The Medical letter on drugs and therapeutics 中科院4区
JCR:Q4
• Volume 66
(1694)，
2024 ，pp. 13
- 14
关键词: adverse effects ；Cequa ；dosage ；dry eye disease ；efficacy ；eye ；Eysuvis ；Lacrisert ；lactation ；lifitegrast ；loteprednol ；Miebo ；ophthalmic cyclosporine ；Optilight ；perfluorohexyloctane ；pregnancy ；Restasis ；safety ；Tyrvaya ；varenicline ；Xiidra
被引量
2
【期刊论文】 • Locatelli, Elyana Vittoria Tessa 1,2,3Acuna, Kelly Ann 1,2,3Betz, Jason 1,2,3Tovar, Arianna Alicia 3
+1位作者
• Cornea 中科院4区
JCR:Q2
• Volume 43
(1)，
2024 ，pp. 88
- 94
摘要： Purpose:The aim of the study was to examine subjective responses to cyclosporine A (CsA) 0.05% versus lifitegrast 5% in individuals with dry eye disease.Methods:This study was a retrospective review of individuals with clinically diagnosed dry eye disease treated with both CsA 0.05% and lifitegrast 5% over the course of their disease. Information collected included demographics, comorbidities, and dry eye disease signs. Treatment preferences were noted as mild or strong for a particular medication, no preference, or unable to tolerate either medication. The primary outcome measure was patient-reported medication preference. The secondary outcome measure was an examination of individual and eye factors that related to medication preference.Results:Sixty-four individuals (mean age 66.73 +/- 13.17 years;82.8% male, 71.9% White, 29.7% Hispanic) used both CsA and lifitegrast over the course of their disease. Of those, 33 preferred CsA (12.5% mildly and 39.1% strongly), 14 preferred lifitegrast (3.1% mildly and 18.8% strongly), 12 had no preference (18.8%), and 5 could not tolerate either medication (7.8%) due to side effects. No demographic characteristics, comorbidities, or ocular surface findings correlated with medication preference.Conclusions:In individuals who used both CsA 0.05% and lifitegrast 5% over the course of their disease, a higher frequency of individuals preferred CsA. No clinical factors correlated with medication preference.
关键词: Restasis ；Xiidra ；antiinflammatory agents ；cyclosporine ；lifitegrast ；dry eye disease
被引量
9
【期刊论文】 • Karpecki, Paul 1
摘要： Background Dry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA (R);OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis (R);CsA), and lifitegrast ophthalmic solution 5% (Xiidra (R);LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT.Methods This real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05.Results Overall, 7102 patients (OTX-101 n = 1846;CsA n = 2248;LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101;OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854).Conclusions Patients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.
关键词: Cyclosporine A ；Discontinuation ；Keratoconjunctivitis sicca ；Persistence
被引量
8
【期刊论文】 • Liu, Xu 1Guo, Heng 1Peng, Peng 2Li, Yaping 3
+5位作者
• ACS OMEGA • Volume 8
(21)，
2023 ，pp. 19072
- 19080
摘要： In the present study, a practical method for synthesizingthe keyintermediate 5,7-dichlorotetrahydroisoquinoline-6-carboxylic acid(1) of Lifitegrast was proposed. First, an investigationwas conducted into the utilization of the impurity and recrystallizationmethod in the synthesis of 5,7-dichlorotetrahydroisoquinoline (5 & BULL;HCl) via Friedel-Crafts cyclization. Throughthe screening of different protection groups, a previously unreportedquaternary ammonium salt (13) was isolated with a 95.9%yield and 99.6% purity by simply adjusting the pH during the carboxylationreaction. Subsequently, free state 1 was obtained bycontrolling the pH to 4-5 with HCl-(aq), thereby avoiding theneed for a free operation in the synthesis of the API of Lifitegrast.Further, the triphenylmethanol (TrOH) was recycled to triphenylmethylchloride (TrCl) using CaCl2/HCl-(aq) with 93.0% yield and98.0% purity.
关键词: High-performance liquid chromatography ；Show More
被引量
1
【期刊论文】 • White, Darrell E. 1Hendrix, Laura H. 2Sun, Lucille 3Tam, Iris 3
+2位作者
• Journal of Managed Care and Specialty Pharmacy • Volume 29
(1)，
2023 ，pp. 69
- 79
摘要： BACKGROUND: Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent head-to-head trial outcomes.OBJECTIVE: To compare the efficacy of OC-01 (varenicline solution) 0.03 mg nasal spray (OC-01 VNS) to lifitegrast 5% oph-thalmic solution on tear production and patient-reported eye dryness in patients with dry eye disease (DED) using data from phase 3 clinical trials via MAIC analysis.METHODS: Individual patient data (IPD) from the phase 3 registrational trial of OC-01 VNS and aggregate data from 2 phase 3 tri-als of lifitegrast in the publicly available XIIDRA New Drug Application were used. Using unanchored MAIC methods, IPD were weighted on clinically relevant baseline variables (age, race, sex, baseline Schirmer's test score [STS], and Eye Dryness Score [EDS]) to produce weighted OC-01 VNS datasets matched to the same lifitegrast datasets' variables. Least-squares (LS) mean change from baseline (CFB) in STS for OC-01 VNS was calculated using the identical analysis of covariance model and covariates used to cal-culate the same values for lifitegrast in the XIIDRA New Drug Application and was thencompared. LS mean EDS (based on a 100 -point Visual Analogue Scale) was compared via analysis of covariance in the weighted OC-01 VNS and lifitegrast datasets. OC-01 VNS at 2 and 4 weeks compared to lifitegrast data at 2 and 6 weeks.RESULTS: Data from 511 subjects (n = 260 treated;251 vehicle control [VC]) in the OC-01 VNS phase 3 trial, 588 (n = 293 treated, 295 VC) in the lifitegrast phase 3 OPUS-1 trial, and 718 (n = 358 treated, 360 VC) in the lifitegrast phase 3 OPUS-2 trial were ana-lyzed. The LS mean STS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 and OPUS-2 (P < 0.0001 for allcomparisons). The LS mean EDS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 (P < 0.0001 for both comparisons) and at 4 weeks vs lifitegrast at 6 weeks in OPUS-2 (P < 0.0001).CONCLUSIONS: This MAIC analysis demonstrates OC-01 VNS produced significantly greater improvement in mean STS and comparable or greater improvement in EDS compared with lifitegrast in phase 3 trials. These findings suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with lifitegrast for the treatment of DED within the conditions of the analysis methodology.
被引量
6
【期刊论文】 • Ghosh, Anita Kirti 1,2,5Bacellar-Galdino, Marianna 5Iqbal, Sana 2,5Pappenhagen, Nathaniel E. 5
+1位作者
• Journal of Ocular Pharmacology and Therapeutics • Volume 38
(4)，
2022 ，pp. 294
- 304
摘要： Purpose: Particulate matter (PM) is a primary cause for the development of acute and chronic dry eye disease, especially irritant-induced conjunctivitis. The purpose of the present study was to determine the effects of fine atmospheric PM on the rabbit ocular surface, and determine the protective effects of a synthetic antioxidant, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), in vitro and in vivo. Methods: Rabbit corneal epithelial cells (SIRC) were exposed to increasing concentrations of PM to determine the effects on cell motility and viability. The in vivo effects of topically instilled PM were tested in New Zealand White rabbits. Comprehensive ophthalmic exams and corneal fluorescein staining were performed. Results: Exposure to PM resulted in dose-dependent cell death and impaired cellular motility;Mn-TM-2-PyP protected against PM-induced cytotoxicity and significantly increased SIRC cell motility. In vivo, exposure to PM (5 mg/ml, topical, 3 times daily for 7 days) resulted in signs of dry eye, notably hyperemia, increased corneal fluorescein staining, and decreased tear volumes. Mn-TM-2-PyP significantly improved hyperemia and corneal fluorescein readouts but had no effect on tear production. Lifitegrast (Xiidra (R)) showed similar pharmacologic efficacy to Mn-TM-2-PyP. Conclusion: Overall, these data provide evidence that PM induces phenotypes of ocular surface disease responsive to antioxidant and immunosuppressant therapy. To our knowledge this is the first report of a large animal model to study PM-induced ocular surface disease. The present work provides standardized experimental paradigms for the comprehensive in vitro and in vivo testing of novel therapeutic approaches targeting PM-induced conjunctivitis and dry-eye.
关键词: ocular surface disease ；dry eye ；conjunctivitis ；cornea ；antioxidant ；lifitegrast ；manganese porphyrin
被引量
6
已选:0 清除
批量下载
批量引用
- 1
- 2