Abstract
Purpose:
To evaluate the potency and efficacy of a library of dopamine receptor D2 (D2R) antagonists in the mitigation of fibrotic activation in retinal pigment epithelial (RPE) cells.
Methods:
ARPE-19 cells were cultured and treated with methotrexate or 27 district D2R antagonists using a fibronectin deposition assay. The most potent compounds were then further assessed in assays measuring cellular proliferation, cellular migration, and profibrotic gene expression.
Results:
The previously established antifibrotic D2R antagonist loxapine exerted a robust and dose-dependent inhibition of fibronectin deposition, whereas methotrexate exerted minimal inhibition. The most potent D2R antagonist identified, fluphenazine, effectively blocked in vitro models of fibrosis at 300–1,000 nM concentrations.
Conclusions:
Here we found multiple FDA-approved D2R antagonists that potently block RPE cell fibrogenesis. These findings further support the potential of D2R antagonism as a potential therapeutic for retinal fibrotic disease.
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