αVβ8 integrin targeting to prevent posterior capsular opacification.

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

SUBMITTER: Shihan MH 

PROVIDER: S-EPMC8663568 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature