{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:32:34Z","timestamp":1771230754182,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,22]],"date-time":"2023-01-22T00:00:00Z","timestamp":1674345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["EY028836"],"award-info":[{"award-number":["EY028836"]}]},{"name":"National Institutes of Health","award":["EY023286"],"award-info":[{"award-number":["EY023286"]}]},{"name":"Research to Prevent Blindness to the Department of Ophthalmology, University of Colorado","award":["EY028836"],"award-info":[{"award-number":["EY028836"]}]},{"name":"Research to Prevent Blindness to the Department of Ophthalmology, University of Colorado","award":["EY023286"],"award-info":[{"award-number":["EY023286"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>With aging, human lenses lose the ability to focus on nearby objects due to decreases in accommodative ability, a condition known as presbyopia. An increase in stiffness or decrease in lens elasticity due to protein aggregation and insolubilization are the primary reasons for presbyopia. In this study, we tested aggrelyte-1 (S,N-diacetyl glutathione diethyl ester) for its ability to promote protein solubility and decrease the stiffness of lenses through its dual property of lysine acetylation and disulfide reduction. Treatment of water-insoluble proteins from aged human lenses (58\u201375 years) with aggrelyte-1 significantly increased the solubility of those proteins. A control compound that did not contain the S-acetyl group (aggrelyte-1C) was substantially less efficient in solubilizing water-insoluble proteins. Aggrelyte-1-treated solubilized protein had significant amounts of acetyllysine, as measured by Western blotting and LC-MS\/MS. Aggrelytes increased the protein-free thiol content in the solubilized protein. Aged mouse (7 months) and human (44\u201366 years) lenses treated with aggrelyte-1 showed reduced stiffness accompanied by higher free thiol and acetyllysine levels compared with those treated with aggrelyte-1C or untreated controls. Our results suggested that aggrelyte-1 reduced lens stiffness through acetylation followed by disulfide reduction. This proof-of-concept study paves the way for developing aggrelyte-1 and related compounds to reverse presbyopia.<\/jats:p>","DOI":"10.3390\/ijms24032196","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Promotion of Protein Solubility and Reduction in Stiffness in Human Lenses by Aggrelyte-1: Implications for Reversing Presbyopia"],"prefix":"10.3390","volume":"24","author":[{"given":"Sudipta","family":"Panja","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, School of Medicine, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-0545","authenticated-orcid":false,"given":"Hanmant","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Rankenberg","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, School of Medicine, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Hyun","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, School of Medicine, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram H.","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, School of Medicine, Aurora, CO 80045, USA"},{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1016\/j.ophtha.2018.04.013","article-title":"Global Prevalence of Presbyopia and Vision Impairment from Uncorrected Presbyopia: Systematic Review, Meta-analysis, and Modelling","volume":"125","author":"Fricke","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1001\/archopht.126.12.1731","article-title":"Global vision impairment due to uncorrected presbyopia","volume":"126","author":"Holden","year":"2008","journal-title":"Arch Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1016\/j.ophtha.2015.04.014","article-title":"The Global Burden of Potential Productivity Loss from Uncorrected Presbyopia","volume":"122","author":"Frick","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10719-020-09961-9","article-title":"Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro","volume":"38","author":"Nandi","year":"2021","journal-title":"Glycoconj. 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