Crenolanib inhibits retinal fibrosis associated with resistance to anti-VEGF in neovascular age-related macular degeneration in retinal Müller cells

Abstract

Abstract Backgorund Anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (NVAMD) may cause fibrosis in primary cultured mouse retinal Müller cells (PMCs), resulting in resistance to treatment. This study aimed to confirm the decrease in the expression of fibrosis-related proteins after treatment with platelet-derived growth factor receptor (PDGFR) inhibitor. Methods PMCs were treated with anti-VEGF, bevacizumab, and PDGF, for 24 and 72 h, and the expression of fibrosis-related proteins, inflammatory cytokines, and PDGFR was confirmed. After 72 h of co-treatment of PMCs with bevacizumab and crenolanib, a PDGFR inhibitor, fibrosis-related protein expression was confirmed. Results When PMCs were treated with 1 mg/mL bevacizumab for 72 h, the expression of VEGF and inflammatory cytokines decreased, and the expression of fibrosis-related proteins and PDGFR-β increased. When PMCs were treated with 100 ng/mL PDGF-B for 72 h, the expression of VEGF and inflammatory cytokines increased, and the expression of fibrosis-related proteins and PDGFR-β decreased. When PMCs were treated with 1 mg/mL bevacizumab and 5 nM crenolanib, the expression of fibrosis-related proteins decreased. Conclusion If PMCs are treated with anti-VEGF agents for a long time, fibrosis may occur that may lead to resistance to NVAMD treatment. When PMCs are treated with anti-VEGF and crenolanib, a PDGFR inhibitor, the expression of fibrosis-related proteins is reduced.