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

Biochem Biophys Res Commun. 2021 Oct 16;582:100-104. doi: 10.1016/j.bbrc.2021.10.036. Online ahead of print.ABSTRACTAniridia 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.PMID:34700241 | DOI:10.1016/j.bbrc.2021.10.036

Source: Cell Research - October 26, 2021 Category: Cytology Authors: Keren Oved L éa Zennaro Orly Dorot Johanna Zerbib Elie Frank Lauriane N Roux Edward Pichinuk Daniel Aberdam Dominique Bremond-Gignac Source Type: research