{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T07:08:17Z","timestamp":1781420897097,"version":"3.54.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82122017"],"award-info":[{"award-number":["82122017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870642"],"award-info":[{"award-number":["81870642"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970780"],"award-info":[{"award-number":["81970780"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670835"],"award-info":[{"award-number":["81670835"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700819"],"award-info":[{"award-number":["81700819"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission","award":["19441900700"],"award-info":[{"award-number":["19441900700"]}]},{"name":"Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission","award":["21S31904900"],"award-info":[{"award-number":["21S31904900"]}]},{"name":"Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Cente","award":["SHDC12019X08"],"award-info":[{"award-number":["SHDC12019X08"]}]},{"name":"Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Cente","award":["SHDC2020CR4078"],"award-info":[{"award-number":["SHDC2020CR4078"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Nine elder cynomolgus monkeys were used, consisting of three monkeys without cataract as controls, three monkeys with naturally occurring cortical cataract, and three monkeys with nuclear cataract as intervention groups. Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract. Fluorescence changes of injected thermogel and cataract progression were observed. Lanosterol concentration in aqueous humor, solubility changes in lens proteins, and oxidative stress levels were analyzed in the lenses of the control and intervention groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Injected thermogel showed decreased fluorescence during follow up. Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased, which was in accordance with the changes in cortical lens clarity. However, lenses with nuclear opacification showed little change. In the cortical region of lenses with cortical cataract, solubility of \u03b1-crystallin was significantly increased after administration of lanosterol, as well as the reduction of oxidative stress.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates. Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages, possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status. Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/pcmedi\/pbac021","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T18:15:46Z","timestamp":1661364946000},"source":"Crossref","is-referenced-by-count":13,"title":["Inhibitory effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system"],"prefix":"10.1093","volume":"5","author":[{"given":"Keke","family":"Zhang","sequence":"first","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"Department of Ophthalmology, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"NHC Key Laboratory of Myopia (Fudan University) , Shanghai 200031, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences , Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"He","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"Department of Ophthalmology, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"NHC Key Laboratory of Myopia (Fudan University) , Shanghai 200031, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences , Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Du","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"Department of Ophthalmology, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"NHC Key Laboratory of Myopia (Fudan University) , Shanghai 200031, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences , Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou 510620, China"},{"name":"Institute for Genomic Medicine, Institute of Engineering in Medicine, and Shiley Eye Institute, University of California , San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Wu","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Smidt Heart Institute , Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou 510620, China"},{"name":"Guangzhou KangRui Biological Pharmaceutical Technology Company , Guangzhou 510440, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"Department of Ophthalmology, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"NHC Key Laboratory of Myopia (Fudan University) , Shanghai 200031, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences , Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Macau University of Science and Technology , Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"Department of Ophthalmology, Eye & ENT Hospital, Fudan University , Shanghai 200031, China"},{"name":"NHC Key Laboratory of Myopia (Fudan University) , Shanghai 200031, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences , Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"2022100304482179700_bib1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0140-6736(05)70803-5","article-title":"Age-related cataract","volume":"365","author":"Asbell","year":"2005","journal-title":"Lancet"},{"key":"2022100304482179700_bib2","first-page":"3669","article-title":"A global view on output and outcomes of cataract surgery with national indices of socioeconomic development","volume":"58","author":"Wang","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022100304482179700_bib3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/ICU.0b013e3283414fc8","article-title":"The global burden of cataract","volume":"22","author":"Rao","year":"2011","journal-title":"Curr Opin Ophthalmol"},{"key":"2022100304482179700_bib4","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/302415a0","article-title":"Short-range order of crystallin proteins accounts for eye lens transparency","volume":"302","author":"Delaye","year":"1983","journal-title":"Nature"},{"key":"2022100304482179700_bib5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/S0167-4838(99)00178-8","article-title":"Eye lens alphaA- and alphaB-crystallin: complex stability versus chaperone-like activity","volume":"1434","author":"van\u00a0Boekel","year":"1999","journal-title":"Biochim Biophys Acta"},{"key":"2022100304482179700_bib6","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol reverses protein aggregation in cataracts","volume":"523","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"2022100304482179700_bib7","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1167\/iovs.05-0890","article-title":"Accommodative changes in lens diameter in rhesus monkeys","volume":"47","author":"Glasser","year":"2006","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022100304482179700_bib8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1167\/iovs.15-18169","article-title":"Nonhuman primate ocular biometry","volume":"57","author":"Augusteyn","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022100304482179700_bib9","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.jcrs.2014.02.034","article-title":"Prevention of capsule opacification after accommodating lens refilling: pilot study of strategies evaluated in a monkey model","volume":"40","author":"Koopmans","year":"2014","journal-title":"J Cataract Refract Surg"},{"key":"2022100304482179700_bib10","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1021\/bm101572j","article-title":"Influence of LA and GA sequence in the PLGA block on the properties of thermogelling PLGA-PEG-PLGA block copolymers","volume":"12","author":"Yu","year":"2011","journal-title":"Biomacromolecules"},{"key":"2022100304482179700_bib11","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/archopht.1993.01090060119035","article-title":"The lens opacities classification system III. The longitudinal study of cataract study group","volume":"111","author":"Chylack","year":"1993","journal-title":"Arch Ophthalmol"},{"key":"2022100304482179700_bib12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11357-018-0006-2","article-title":"Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys","volume":"40","author":"Robinson","year":"2018","journal-title":"Geroscience"},{"key":"2022100304482179700_bib13","doi-asserted-by":"crossref","first-page":"e0192718","DOI":"10.1371\/journal.pone.0192718","article-title":"Study of retina and choroid biological parameters of rhesus monkeys eyes on scleral collagen cross-linking by riboflavin and ultraviolet A","volume":"13","author":"Sun","year":"2018","journal-title":"PLoS ONE"},{"key":"2022100304482179700_bib14","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1016\/j.biomaterials.2013.01.013","article-title":"A long-acting formulation of a polypeptide drug exenatide in treatment of diabetes using an injectable block copolymer hydrogel","volume":"34","author":"Li","year":"2013","journal-title":"Biomaterials"},{"key":"2022100304482179700_bib15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.actbio.2015.05.005","article-title":"Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel","volume":"23","author":"Zhang","year":"2015","journal-title":"Acta Biomater"},{"key":"2022100304482179700_bib16","doi-asserted-by":"crossref","first-page":"6400","DOI":"10.1039\/C7TB01556A","article-title":"Sustained subconjunctival delivery of cyclosporine A using thermogelling polymers for glaucoma filtration surgery","volume":"5","author":"Sun","year":"2017","journal-title":"J Mater Chem B"},{"key":"2022100304482179700_bib17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.chroma.2017.08.081","article-title":"Quantitation of lanosterol in the vitreous humor of rabbits after ocular administration of lanosterol\/thermogel formulation by ultra high performance liquid chromatography-tandem mass spectrometry with the electrospray ionization mode","volume":"1519","author":"Lv","year":"2017","journal-title":"J Chromatogr A"},{"key":"2022100304482179700_bib18","doi-asserted-by":"crossref","first-page":"13601","DOI":"10.1016\/S0021-9258(17)36872-2","article-title":"The chaperone activity of bovine alpha crystallin. Interaction with other lens crystallins in native and denatured states","volume":"269","author":"Wang","year":"1994","journal-title":"J Biol Chem"},{"key":"2022100304482179700_bib19","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1074\/jbc.M308203200","article-title":"Amyloid fibril formation by lens crystallin proteins and its implications for cataract formation","volume":"279","author":"Meehan","year":"2004","journal-title":"J Biol Chem"},{"key":"2022100304482179700_bib20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cmet.2005.01.001","article-title":"Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterol","volume":"1","author":"Song","year":"2005","journal-title":"Cell Metab"},{"key":"2022100304482179700_bib21","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.bbrc.2018.10.175","article-title":"Lanosterol and 25-hydroxycholesterol dissociate crystallin aggregates isolated from cataractous human lens via different mechanisms","volume":"506","author":"Chen","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"2022100304482179700_bib22","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.exer.2004.12.007","article-title":"Age-related nuclear cataract-oxidation is the key","volume":"80","author":"Truscott","year":"2005","journal-title":"Exp Eye Res"},{"key":"2022100304482179700_bib23","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1167\/iovs.07-1151","article-title":"Free and bound water in normal and cataractous human lenses","volume":"49","author":"Heys","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022100304482179700_bib24","doi-asserted-by":"crossref","first-page":"118617","DOI":"10.1016\/j.bbamcr.2019.118617","article-title":"Lanosterol modulates proteostasis via dissolving cytosolic sequestosomes\/aggresome-like induced structures","volume":"1867","author":"Hu","year":"2020","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"2022100304482179700_bib25","doi-asserted-by":"crossref","first-page":"8479","DOI":"10.1021\/jacs.8b03065","article-title":"Lanosterol disrupts aggregation of human \u03b3D-crystallin by binding to the hydrophobic dimerization interface","volume":"140","author":"Kang","year":"2018","journal-title":"J Am Chem Soc"},{"key":"2022100304482179700_bib26","first-page":"677","article-title":"Age-dependent changes in the structure of alpha crystallin","volume":"10","author":"Spector","year":"1971","journal-title":"Invest Ophthalmol"},{"key":"2022100304482179700_bib27","first-page":"130","article-title":"The search for a solution to senile cataracts Proctor lecture","volume":"25","author":"Spector","year":"1984","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022100304482179700_bib28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijbiomac.2021.08.111","article-title":"Pathogenic mechanism of congenital cataract caused by the CRYBA1\/A3-G91del variant and related intervention strategies","volume":"189","author":"Xu","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"2022100304482179700_bib29","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1126\/science.aac9145","article-title":"Pharmacological chaperone for \u03b1-crystallin partially restores transparency in cataract models","volume":"350","author":"Makley","year":"2015","journal-title":"Science"},{"key":"2022100304482179700_bib30","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.21037\/atm-20-1960","article-title":"Advances in pharmacotherapy of cataracts","volume":"8","author":"Xu","year":"2020","journal-title":"Ann Transl Med"},{"key":"2022100304482179700_bib31","doi-asserted-by":"crossref","first-page":"8459","DOI":"10.1038\/s41598-019-44676-4","article-title":"Failure of oxysterols such as lanosterol to restore lens clarity from cataracts","volume":"9","author":"Daszynski","year":"2019","journal-title":"Sci Rep"},{"key":"2022100304482179700_bib32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4103\/0301-4738.121141","article-title":"Etiopathogenesis of cataract: an appraisal","volume":"62","author":"Gupta","year":"2014","journal-title":"Indian J Ophthalmol"},{"key":"2022100304482179700_bib33","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.exer.2008.05.018","article-title":"Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerations","volume":"88","author":"Brennan","year":"2009","journal-title":"Exp Eye Res"},{"key":"2022100304482179700_bib34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1006\/exer.2001.1165","article-title":"Glutathione and NADH, but not ascorbate, protect lens proteins from modification by UV filters","volume":"74","author":"Taylor","year":"2002","journal-title":"Exp Eye Res"},{"key":"2022100304482179700_bib35","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1089\/rej.2009.1009","article-title":"Age-dependent denaturation of enzymes in the human lens: a paradigm for organismic aging?","volume":"13","author":"Zhu","year":"2010","journal-title":"Rejuvenation Res"},{"key":"2022100304482179700_bib36","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1006\/exer.1998.0549","article-title":"An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract","volume":"67","author":"Sweeney","year":"1998","journal-title":"Exp Eye Res"},{"key":"2022100304482179700_bib37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/00001648-199305000-00003","article-title":"Plasma antioxidants and risk of cortical and nuclear cataract","volume":"4","author":"Vitale","year":"1993","journal-title":"Epidemiology"}],"container-title":["Precision Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pcm\/advance-article-pdf\/doi\/10.1093\/pcmedi\/pbac021\/45510900\/pbac021.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pcm\/article-pdf\/5\/3\/pbac021\/46305738\/pbac021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pcm\/article-pdf\/5\/3\/pbac021\/46305738\/pbac021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T04:48:59Z","timestamp":1664772539000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pcm\/article\/doi\/10.1093\/pcmedi\/pbac021\/6674682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,9,30]]}},"URL":"https:\/\/doi.org\/10.1093\/pcmedi\/pbac021","relation":{},"ISSN":["2096-5303","2516-1571"],"issn-type":[{"value":"2096-5303","type":"print"},{"value":"2516-1571","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2022,8,24]]},"article-number":"pbac021"}}