iPSC-derived retinal organoids

3D retina derived from patient iPSCs has been shown to be a useful tool in elucidating disease mechanisms, including studies of Retinitis Pigmentosa (RP). RP is one of the most common inherited forms of retinal degeneration and affects more than 1 million people worldwide. It is characterised by progressive visual loss leading to night blindness and visual field constriction eventually leading to the loss of central vision. Management of RP remains challenging with no effective treatments currently available. Photoreceptors, in particular rods at the early stages of the disease, and retinal pigment epithelium (RPE) are the most affected cells in RP.  

IPSC-derived 3D optic cups provide an unprecedented tool to study the mechanism of RP using a physiologically-relevant model, which is especially useful in modelling genetically heterogeneous diseases such as RP. Last year, researchers at the University of Edinburgh used retinal organoids to gain mechanistic insight into the development of an X-linked form of RP caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene, which gives instructions for making the RPGR protein localised in photoreceptor connecting cilium (doi: 10.1038/s41467-017-00111-8).  

Interestingly, mutations in ubiquitously expressed genes can also give rise to retina-specific phenotype seen in RP patients. One of such genes is pre-mRNA processing factor 31 (PRPF31) involved in catalysing pre-mRNA splicing. Animal models do no recapitulate the RP phenotype caused by PRPF mutations in humans.  

Professor Majlinda Lako and a team of collaborators, including Professor Reinhard Lührmann, Dr Sushma-Nagaraja Grellscheid and Professor Colin Johnson, used iPSC-derived retinal organoids and RPE to shed light on the mechanism of retinal degeneration seen in patients with PRPF31 gene mutation. The researchers were able to provide molecular characterisation of RP clinical phenotype.