In the context of the retinal vasculature, stimulation of FZD4:LRP5 signaling may provide benefits in FEVR or other rare congenital diseases that harbor mutations within Wnt pathway components but could also help mitigate the vascular leakage associated with neovascularization in various clinical settings including diabetic retinopathy and wet macular degeneration that represent clinical unmet needs. The gene discussed is FZD4; the disease is age-related macular degeneration.