Wnt Signaling in vascular eye diseases

The Wnt signaling pathway plays a pivotal role in vascular morphogenesis in various organs including the eye. Wnt ligands and receptors are key regulators of ocular angiogenesis both during the eye development and in vascular eye diseases. Wnt signaling participates in regulating multiple vascular beds in the eye including regression of the hyaloid vessels, and development of structured layers of vasculature in the retina. Loss-of-function mutations in Wnt signaling components cause rare genetic eye diseases in humans such as Norrie disease, and familial exudative vitreoretinopathy (FEVR) with defective ocular vasculature. On the other hand, experimental studies in more prevalent vascular eye diseases, such as wet age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), and corneal neovascularization, suggest that aberrantly increased Wnt signaling is one of the causations for pathological ocular neovascularization, indicating the potential of modulating Wnt signaling to ameliorate pathological angiogenesis in eye diseases. This review recapitulates the key roles of the Wnt signaling pathway during ocular vascular development and in vascular eye diseases, and pharmaceutical approaches targeting the Wnt signaling as potential treatment options.