2. Academic Validation
  3. Survey of Dopamine Receptor D2 Antagonists as Retinal Antifibrotics

Survey of Dopamine Receptor D2 Antagonists as Retinal Antifibrotics

  • J Ocul Pharmacol Ther. 2024 Oct;40(8):536-542. doi: 10.1089/jop.2024.0006.
Ashley Y Gao 1 2,  Madison G Whaley 1,  Namita Saraf 1,  Sophie J Bakri 1,  Andrew J Haak 3 4
Affiliations

Affiliations

  • 1 Mayo Clinic, Department of Ophthalmology, Rochester, Minnesota, USA.
  • 2 University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • 3 Mayo Clinic, Department of Physiology and Biomedical Engineering, Rochester, Minnesota, USA.
  • 4 Mayo Clinic, Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, Minnesota, USA.
PMID: 39206555 DOI: 10.1089/jop.2024.0006
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.

Keywords

D2 antagonist; dopamine; fibrosis; ocular; proliferative vitreoretinopathy; retina.

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