Levodopa in retinal disease: Dopamine pathways, neuroprotective mechanisms, and clinical evidence

We review the role of levodopa (L-DOPA), a dopamine precursor used to treat Parkinson disease, as a candidate for retinal neuroprotection, focusing on retinal dopamine biology, mechanisms of action, and evidence from preclinical and clinical studies. Selected experimental and clinical studies indicate that L-DOPA and related dopaminergic interventions influence multiple retinal pathways relevant to degeneration. L-DOPA, synthesized in the pigmented retinal pigment epithelium, activates GPR143 signaling and promotes the release of neuroprotective factors. In animal studies, L-DOPA supplementation rescued retinal development in albinism and reduced oxidative damage to photoreceptors. Epidemiologic analyses showed that patients on systemic L-DOPA had a delayed onset and a lower incidence of age-related macular degeneration (AMD). Small clinical studies in neovascular AMD demonstrated that adjunctive oral L-DOPA improved vision and reduced the burden of anti-vascular endothelial growth factor injections. Larger controlled trials are needed to define efficacy, optimal dosing, and long-term tolerability. Given its established pharmacology and ability to cross the blood-retinal barrier, L-DOPA is a promising candidate for therapeutic repurposing in ophthalmology.