TY  - UNPB
A1  - Ramsden, C
UR  - https://discovery.ucl.ac.uk/id/eprint/10027960/
N2  - Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of cellular material to study. This research used fibroblast-derived induced pluripotent stem cells (iPSC) to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. The patient phenotype, fibroblasts, iPSC and RPE were fully characterised at the DNA, RNA, protein and functional levels and compared to a control. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and based on this, the MERTK-RPE cells were subsequently treated with two translational read-through inducing drugs to investigate potential restoration of expression of the affected gene and production of a full-length protein. One of the drugs was able to reinstate phagocytosis of labelled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis, drug screening potential and treatments for these rare and blinding disorders.
AV  - public
EP  - 255
KW  - Retina
KW  -  stem cell
KW  -  retinitis pigmentosa
KW  -  mertk
KW  -  inherited retinal disease
ID  - discovery10027960
SP  - 1
N1  - Unpublished
PB  - UCL (University College London)
TI  - Using stem cells to model MERTK deficient retinitis pigmentosa
Y1  - 2017/11/28/
M1  - Doctoral
ER  -