| First Author | Shihan MH | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 21 | PubMed ID | 34554928 |
| Mgi Jnum | J:336470 | Mgi Id | MGI:6836399 |
| Doi | 10.1172/jci.insight.145715 | Citation | Shihan MH, et al. (2021) alphaVbeta8 integrin targeting to prevent posterior capsular opacification. JCI Insight 6(21):e145715 |
| abstractText | Fibrotic posterior capsular opacification (PCO), a major complication of cataract surgery, is driven by transforming growth factor-beta (TGF-beta). Previously, alphaV integrins were found to be critical for the onset of TGF-beta-mediated PCO in vivo; however, the functional heterodimer was unknown. Here, beta8 integrin-conditional knockout (beta8ITG-cKO) lens epithelial cells (LCs) attenuated their fibrotic responses, while both beta5 and beta6 integrin-null LCs underwent fibrotic changes similar to WT at 5 days post cataract surgery (PCS). RNA-Seq revealed that beta8ITG-cKO LCs attenuated their upregulation of integrins and their ligands, as well as known targets of TGF-beta-induced signaling, at 24 hours PCS. Treatment of beta8ITG-cKO eyes with active TGF-beta1 at the time of surgery rescued the fibrotic response. Treatment of WT mice with an anti-alphaVbeta8 integrin function blocking antibody at the time of surgery ameliorated both canonical TGF-beta 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 alphaVbeta8 integrin is a major regulator of TGF-beta activation by LCs PCS and that therapeutics targeting alphaVbeta8 integrin could be effective for fibrotic PCO prevention and treatment. |
