Abstract
Presentation Description :
Corneal scarring caused by injury or disease is a significant cause of blindness worldwide. Integrins are key regulators of scar formation and fibrotic outcomes in all tissues. An increase in alphaV-containing integrins on the cell surface of myofibroblasts is a major contributor to scarring. Genetic screening of primary corneal myofibroblasts revealed an upregulation of ubiquitin-mediating enzymes that control integrin turn-over. We found that after wounding, upregulation of deubiquitinases (DUBs) shift the balance towards integrin accumulation by removing ubiquitin from alphav-integrins, in turn preventing normal integrin degradation. The presentation will describe the basic science behind integrins as anti-scarring targets and the use of a single topical application of self-delivery siRNA targeting DUBs to prevent scarring in ex vivo and in vivo models.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.