Verteporfin regulates corneal neovascularization through inhibition of YAP protein activation

As a transparent and avascular tissue, cornea is one of the most important refractive structures of the eye. At present, a variety insults can cause corneal neovascularization (CNV). CNV is a vision-threatening disease that is becoming a growing public health concern. The estimated prevalence of CNV is about 4.14%, 12% of whom suffered subsequent vision loss (Lee et al., 1998).

Angiogenesis is a multifactorial and multistep process including the sprouting angiogenesis, vascular barrier maturation and new blood vessel formation(Chung and Ferrara, 2011; Potente et al., 2011). During the complicated process, various signaling pathways are involved, such as VEGF/VEGFR, Wnt and Hippo (Boopathy and Hong, 2019; Coultas et al., 2005; Nagy et al., 2007; Pulkkinen et al., 2021; Zerlin et al., 2008). Recent study have shown that YAP (yes-associated protein), the effectors of Hippo pathway, are essential for vascular development (Boopathy and Hong, 2019; Pulkkinen et al., 2021; Wang et al., 2017). YAP can activate the remodeling of actin cytoskeleton, and play a promoting role in sprouting angiogenesis and pathological angiogenesis (Choi et al., 2015; Kim et al., 2017). In addition, actin dynamics is critical for vasculogenic mimicry and cofilin play a key role in this mechanism(Kumar et al., 2016; Nakajima et al., 2023).

Verteporfin (VP) is a classical inhibitor of the YAP-TEAD complex, which is used for clinical treatment of neovascular macular degeneration through photodynamic therapy (Horton, 2007; Scott and Goa, 2000; Wei et al., 2017; Wormald et al., 2007). Interestingly, other studies found that VP can inhibit the growth of retinoblastoma cells and breast cancer cells without photoactivation (Brodowska et al., 2014; Wei and Li, 2020). However, the role of YAP in CNV is not completely understood and the potential role of VP in CNV remains unknown. Therefore, we performed this study to evaluate the role and mechanism of VP during the CNV.

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