DRD2 activation inhibits choroidal neovascularization in patients with Parkinson's disease and age-related macular degeneration.
Fiche publication
Date publication
juillet 2024
Journal
The Journal of clinical investigation
Auteurs
Membres identifiés du Cancéropôle Est :
Pr QUANTIN Catherine
Tous les auteurs :
Mathis T, Baudin F, Mariet AS, Augustin S, Bricout M, Przegralek L, Roubeix C, Benzenine É, Blot G, Nous C, Kodjikian L, Mauget-Faÿsse M, Sahel JA, Plevin R, Zeitz C, Delarasse C, Guillonneau X, Creuzot-Garcher C, Quantin C, Hunot S, Sennlaub F
Lien Pubmed
Résumé
Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. L-DOPA-treated Parkinson Disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models, combining 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and laser-induced nAMD, standard PD treatment of L-DOPA/DOPA-decarboxylase inhibitor, or specific dopamine receptor inhibitors, we here demonstrate that L-DOPA treatment-induced increase of dopamine mediated dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than two hundred thousand nAMD patients receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2-agonist treated (PD) patients have a significantly delayed age of onset for nAMD (81.4 (±7.0) vs 79.4 (±8.1) years old, respectively, p<0.0001) and reduced need for anti-VEGF therapies (-0.6 injections per 100 mg/day daily dose of DRD2 agonists the second year of treatment), similar to the L-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in nAMD patients.
Mots clés
Neurodegeneration, Neuroscience, Ophthalmology, Parkinson disease, Retinopathy
Référence
J Clin Invest. 2024 07 16;: