DRD2 activation inhibits choroidal neovascularization in patients with Parkinson’s disease and age-related macular degeneration - Centre de recherche en Épidémiologie et Santé des Populations
Article Dans Une Revue The Journal of clinical investigation Année : 2024

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

Thibaud Mathis
Cécile Delarasse
Xavier Guillonneau
Florian Sennlaub

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.

Domaines

Organes des sens
Fichier principal
Vignette du fichier
mathis_2024_in_press_j_clin_invest.pdf (15.43 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
licence

Dates et versions

hal-04667733 , version 1 (05-08-2024)

Licence

Identifiants

Citer

Thibaud Mathis, Florian Baudin, Anne-Sophie Mariet, Sébastien Augustin, Marion Bricout, et al.. DRD2 activation inhibits choroidal neovascularization in patients with Parkinson’s disease and age-related macular degeneration. The Journal of clinical investigation, 2024, 134 (17), pp.e174199. ⟨10.1172/JCI174199⟩. ⟨hal-04667733⟩
79 Consultations
10 Téléchargements

Altmetric

Partager

More