Forschung & Innovation
Publikationen
Angiopoietin-2 and vascular endothelial growth factor α inhibition by faricimab reduces pericyte-to-myofibroblast transition and the myofibroblast phenotype in vitro
PMU Autor*innen
Andreas Koller, Julia Preishuber-Pflügl, Susanne Maria Migschitz, Christian Runge, Markus Lenzhofer, Herbert Anton Reitsamer, Andrea Trost
Alle Autor*innen
Andreas Koller, Julia Preishuber-Pflügl, Susanne Maria Migschitz, Nicola Aponi Pichler, Christian Runge, Markus Lenzhofer, Herbert Anton Reitsamer, Andrea Trost
Fachzeitschrift
EXPERIMENTAL EYE RESEARCH
Kurzfassung
Pericytes (PCs) are essential components of the retinal microvasculature and exhibit fibrotic activity, which is crucial for tissue repair and regeneration. However, chronic fibrotic activity can lead to harmful fibrosis that impairs retinal function. Treatment with faricimab, which targets angiopoietin-2 and vascular endothelial growth factor alpha (VEGF alpha) to prevent neovascularization in diabetic macular edema (DME), reduces epiretinal membrane (ERM) formation in DME, suggesting that faricimab has antifibrotic properties. Because PCs play an important role in fibrosis, we investigated the effects of faricimab on the pericyte-to-myofibroblast transition (PMT) in vitro. To induce PMT and generate myofibroblasts, primary human retinal PCs were treated with TGF-(31. Treatment with TGF-(31 reduced the VEGF alpha consumption of PCs in growth medium and increased the expression of alpha 5(31 integrin, an angiopoietin-2 receptor. Interestingly, treatment with faricimab reduced the migratory capacity of PCs. Furthermore, faricimab treatment resulted in decreased levels of three fibrotic markers, fibronectin, F-actin, and alpha-smooth muscle actin (alpha SMA), during PMT and reduced fibronectin levels in transdifferentiated myofibroblasts. Inhibiting angiopoietin-2 and VEGF alpha decreased SMAD2 activity in myofibroblasts and increased total ERK 1/2 levels during PMT. In conclusion, faricimab reduced both PMT and myofibroblast activity in vitro. Although cell types other than PCs are also involved in retinal fibrosis, the inhibition of PC fibrotic activity by faricimab indicates that angiopoietin-2 and VEGF alpha play profibrotic roles in retinal diseases. These findings support the observation that patients with DME have reduced ERM formation after treatment with faricimab. Consequently, inhibiting angiopoietin-2 and VEGF alpha is a promising approach for modulating tissue fibrosis in retinal diseases and other conditions.