αVβ8 integrin targeting to prevent posterior capsular opacification
| Author(s) | Shihan, Mahbubul H. | |
| Author(s) | Novo, Samuel G. | |
| Author(s) | Wang, Yan | |
| Author(s) | Sheppard, Dean | |
| Author(s) | Atakilit, Amha | |
| Author(s) | Arnold, Thomas D. | |
| Author(s) | Rossi, Nicole M. | |
| Author(s) | Faranda, Adam P. | |
| Author(s) | Duncan, Melinda K. | |
| Date Accessioned | 2022-01-05T20:21:18Z | |
| Date Available | 2022-01-05T20:21:18Z | |
| Publication Date | 2021-09-23 | |
| Description | This article was originally published in JCI Insight. The version of record is available at: https://doi.org/10.1172/jci.insight.145715 | en_US |
| Abstract | Fibrotic posterior capsular opacification (PCO), a major complication of cataract surgery, is driven by transforming growth factor–β (TGF-β). Previously, αV integrins were found to be critical for the onset of TGF-β–mediated PCO in vivo; however, the functional heterodimer was unknown. Here, β8 integrin–conditional knockout (β8ITG-cKO) lens epithelial cells (LCs) attenuated their fibrotic responses, while both β5 and β6 integrin–null LCs underwent fibrotic changes similar to WT at 5 days post cataract surgery (PCS). RNA-Seq revealed that β8ITG-cKO LCs attenuated their upregulation of integrins and their ligands, as well as known targets of TGF-β–induced signaling, at 24 hours PCS. Treatment of β8ITG-cKO eyes with active TGF-β1 at the time of surgery rescued the fibrotic response. Treatment of WT mice with an anti-αVβ8 integrin function blocking antibody at the time of surgery ameliorated both canonical TGF-β signaling and LC fibrotic response PCS, and treatment at 5 days PCS, after surgically induced fibrotic responses were established, largely reversed this fibrotic response. These data suggest that αVβ8 integrin is a major regulator of TGF-β activation by LCs PCS and that therapeutics targeting αVβ8 integrin could be effective for fibrotic PCO prevention and treatment. | en_US |
| Sponsor | This study was supported by NIH grant EY015279 to MKD, NMR’s research fellowships from the University of Delaware Undergraduate Research program, Delaware INBRE (P20 GM103446), the State of Delaware–supported University of Delaware Center for Bioimaging, and 1S10 (RR027273-01), which funded the acquisition of the confocal microscope used in this study. Conflict of interest: DS is a cofounder of Pliant Therapeutics, is on the Scientific Review Board for Genentech and xCella, and has obtained research support from AbbVie, Pfizer, Shang Pharma, and Pliant Therapeutics. A provisional patent application was filed in December 2019 titled “Prevention of posterior capsular opacification with integrin αVβ8 blocking antibody” by inventors DS, MKD, AA, and MHS; application number: US 62/944,151. | en_US |
| Citation | Shihan, Mahbubul H., Samuel G. Novo, Yan Wang, Dean Sheppard, Amha Atakilit, Thomas D. Arnold, Nicole M. Rossi, Adam P. Faranda, and Melinda K. Duncan. 2021. “ΑVβ8 Integrin Targeting to Prevent Posterior Capsular Opacification.” JCI Insight 6 (21). https://doi.org/10.1172/jci.insight.145715. | en_US |
| ISSN | 2379-3708 | |
| URL | https://udspace.udel.edu/handle/19716/29922 | |
| Language | en_US | en_US |
| Publisher | JCI Insight | en_US |
| Title | αVβ8 integrin targeting to prevent posterior capsular opacification | en_US |
| Type | Article | en_US |
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