DRD2 activation inhibits choroidal neovascularization in patients with Parkinson's disease and age-related macular degeneration

Mathis, Thibaud and Baudin, Florian and Mariet, Anne-Sophie and Augustin, Sébastien and Bricout, Marion and Przegralek, Lauriane and Roubeix, Christophe and Benzenine, Éric and Blot, Guillaume and Nous, Caroline and Kodjikian, Laurent and Mauget-Faÿsse, Martine and Sahel, José-Alain and Plevin, Robin and Zeitz, Christina and Delarasse, Cécile and Guillonneau, Xavier and Creuzot-Garcher, Catherine and Quantin, Catherine and Hunot, Stéphane and Sennlaub, Florian (2024) DRD2 activation inhibits choroidal neovascularization in patients with Parkinson's disease and age-related macular degeneration. Journal of Clinical Investigation. ISSN 0021-9738 (https://doi.org/10.1172/JCI174199)

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Abstract

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

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