Retigabine increases the conformational stability of the visual photoreceptor rhodopsin

Abstract

Rhodopsin is the key photoreceptor protein that mediates vision in low-light conditions. Mutations in rhodopsin are the cause of retinal degenerative diseases such as retinitis pigmentosa. Some of these mutations cause a decreased stability of the receptor. It is, therefore, of interest to find new approaches that can help improving rhodopsin conformational stability. In this study, we have analyzed the effect of retigabine, an anticonvulsant formerly used to treat epilepsy, on rhodopsin thermal stability, regeneration capacity, and signal transduction by means of UV–visible and fluorescence spectroscopic techniques. We find that retigabine enhances the thermal stability of dark-state rhodopsin and improves chromophore regeneration without disrupting the photobleaching process. Furthermore, retigabine does not significantly affect transducin activation. These results provide novel insights into the potential therapeutic applications of retigabine in the treatment of retinitis pigmentosa caused by rhodopsin mutations that cause a decreased stability of the mutated receptors.

This research was funded by grants from Ministry of Science and Innovation, Spain (PID2019-104817GB-I00), and from the Government of Catalonia to Research Consolidated Groups (2021 SGR 00342) to P.G. F. W. is the recipient of a predoctoral grant from the Secretariat for Universities and Research of the Ministry of Business and Knowledge, Government of Catalonia and the European Social Fund (2021 FI_B 00228).

Peer Reviewed

Postprint (published version)