TY - JOUR AU - Shihan, Mahbubul H. AU - Novo, Samuel G. AU - Wang, Yan AU - Sheppard, Dean AU - Atakilit, Amha AU - Arnold, Thomas D. AU - Rossi, Nicole M. AU - Faranda, Adam P. AU - Duncan, Melinda K. T1 - αVβ8 integrin targeting to prevent posterior capsular opacification PY - 2021/11/08/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.145715 VL - 6 IS - 21 UR - https://doi.org/10.1172/jci.insight.145715 PB - The American Society for Clinical Investigation ER -