Rescue of MerTK retinitis pigmentosa using a human induced pluripotent stem cell disease model

Abstract

Purpose : Inherited retinopathies are fast becoming the leading cause of blindness in developed countries. In order to counter this heterogeneous group of diseases, adequate disease models need to be developed in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer us a new and radicle way to recapitulate the disease in the dish and give us almost limitless material to drive discovery.

Methods : Fibroblast derived stem cells were used to generate RPE from a patient suffering from retinitis pigmentosa due to a deficiency in MerTK. The MerTK deficiency arises from a nonsense mutation causing a premature stop codon. These RPE cells were fully characterised and then exposed to a drug screen of read-through agents to force expression of the whole length protein.

Results : Two candidate read-through agents were able to force translation through the premature stop codon. The G418 and PTC124 compounds had the best effect at restoring a full length MerTK protein phenotype.

Conclusions : These findings represent a promising avenue of drug discovery in order to treat this rare and devastating disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.