Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease

doi:10.2147/IJN.S403337

科研成果详情

题名	Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease
作者	Lou, Qi1; Pan, Lu 1; Xiang, Shengjin1,2; Li, Yueting1; Jin, Jiahui 1; Tan, Jingyang1; Huang, Baoshan1,2; Nan, Kaihui1,2; Lin, Sen1,2
发表日期	2023
发表期刊	INTERNATIONAL JOURNAL OF NANOMEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	melatonin liposome dry eye disease benzalkonium chloride pyroptosis NLRP3 Caspase-1 GSDMD signaling axis
其他关键词	GASDERMIN D ; ANTIOXIDANT ; DELIVERY ; EPIDEMIOLOGY ; CELLS ; DRUG
摘要	Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED). Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael's addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction. Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission. Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.
资助项目	Wenzhou Medical University[J02-20190202,YNZD2201901];Zhejiang Provincial Natural Science Foundation of China[LQ23H120002,LY19H120002];Basic Research Project of Wenzhou City[Y20210195,ZY2021018];
出版者	DOVE MEDICAL PRESS LTD
ISSN	1178-2013
EISSN	1178-2013
卷号	18 页码:2447-2463
DOI	10.2147/IJN.S403337
页数	17
WOS类目	Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
WOS研究方向	Science & Technology - Other Topics ; Pharmacology & Pharmacy
WOS记录号	WOS:000989764900001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37192892
SCOPUSEID	2-s2.0-85159483821
通讯作者地址	[Nan, Kaihui]School of Ophthalmology & Optometry and Eye Hospital,Wenzhou Medical University,Wenzhou,325027,China ; [Lin, Sen]School of Ophthalmology & Optometry and Eye Hospital,Wenzhou Medical University,Wenzhou,325027,China
Scopus学科分类	Biophysics;Bioengineering;Biomaterials;Pharmaceutical Science;Drug Discovery;Organic Chemistry
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180191
专题	眼视光学院（生物医学工程学院）、附属眼视光医院仁济学院_眼视光、生物医学工程学部
通讯作者	Nan, Kaihui; Lin, Sen
作者单位	1.National Engineering Research Center of Ophthalmology and Optometry,School of Biomedical Engineering,Wenzhou Medical University,Wenzhou,325027,China; 2.State Key Laboratory of Ophthalmology,Optometry and Vision Science,School of Ophthalmology & Optometry,Wenzhou Medical University,Wenzhou,325027,China
第一作者单位	眼视光、生物医学工程学部
通讯作者单位	眼视光学院（生物医学工程学院）、附属眼视光医院
第一作者的第一单位	眼视光、生物医学工程学部
推荐引用方式 GB/T 7714	Lou, Qi,Pan, Lu,Xiang, Shengjin,et al. Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2023,18:2447-2463.
APA	Lou, Qi., Pan, Lu., Xiang, Shengjin., Li, Yueting., Jin, Jiahui., ... & Lin, Sen. (2023). Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease. INTERNATIONAL JOURNAL OF NANOMEDICINE, 18, 2447-2463.
MLA	Lou, Qi,et al."Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease".INTERNATIONAL JOURNAL OF NANOMEDICINE 18(2023):2447-2463.