Ritanserin, a potent serotonin 2A receptor antagonist, represses MEK/ERK signalling pathway to restore PAX6 production and function in aniridia-like cellular model

Keren Oved, Léa Zennaro, Orly Dorot, Johanna Zerbib, Elie Frank, Lauriane N. Roux, Edward Pichinuk, Daniel Aberdam, Dominique Bremond-Gignac

Research output: Contribution to journalArticlepeer-review

Abstract

Aniridia is a panocular inherited rare eye disease linked to heterozygous mutations on the PAX6 gene, which fail to properly produce sufficient protein essential for normal eye development and function. Most of the patients suffer from aniridia-related keratopathy, a progressive opacification of the cornea. There is no effective treatment for this blinding disease. Here we screen for small compounds and identified Ritanserin, a serotonin 2A receptor antagonist, that can rescue PAX6 haploinsufficiency of mutant limbal cells, defective cell migration and PAX6-target gene expression. We further demonstrated that Ritanserin activates PAX6 production through the selective inactivation of the MEK/ERK signaling pathway. Our data strongly suggest that repurposing this therapeutic molecule could be effective in preventing or treating existing blindness by restoring corneal transparency.

Original languageEnglish
Pages (from-to)100-104
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume582
DOIs
StatePublished - 10 Dec 2021
Externally publishedYes

Keywords

  • Congenital aniridia
  • Keratopathy
  • Limbal stem cells
  • PAX6
  • Ritanserin
  • Serotonin

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