Dopamine inhibits retinal pathological neovascularization in the oxygen‐induced retinopathy mouse model

Pathological neovascularization is the leading cause of childhood blindness in retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor agents are commonly used to treat this condition, yet their variable efficacy and off-target effects demand alternative strategies. Here, we investigated the relationship between retinal dopamine (DA) dynamics and pathological angiogenesis in the oxygen-induced retinopathy (OIR) mouse model mimicking ROP pathogenesis. We determined the individual effects of apomorphine (APO), a non-selective DA receptor agonist, and selective agonists or antagonists of dopamine D1 receptor (Drd1) and dopamine D2 receptor (Drd2), on pathological neovascularization. Integrating single-cell RNA sequencing with Müller cell-specific Drd2 knockout OIR mice, we identified that Drd2-mediated signaling in Müller cells orchestrates hypoxia-inducible factor alpha and vascular endothelial growth factor A biosynthesis in Müller cells during the hypoxic-ischemic phase of OIR. Collectively, OIR-induced dopaminergic deficiency and impaired Drd2 activity in Müller cells synergistically exacerbate pathological angiogenesis.