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1  Instituto de Investigación Sanitaria Hospital 12 de Octubre
Academic Editor: Masaru Tanaka


Dominant optic atrophy (DOA) is one of the most frequent forms of hereditary optic neuropathy. This condition is mainly triggered by pathogenic variants in OPA1, which plays a key role in mitochondrial dynamics, cell survival, oxidative phosphorylation or the maintenance of mitochondrial DNA. Mutations in OPA1 cause a decrease of energy production capacity and the degeneration of retinal ganglion cells (RGCs), leading to optic nerve atrophy and reduced visual acuity. Currently, there is no effective treatment for DOA due in part to the lack of an appropriated disease model. The main objective of this work has been the use of induced pluripotent stem cell (iPSC) technology as a tool for the generation of patient-specific iPSC-derived RGCs. For this purpose, we have used an iPSC line previously created from fibroblasts obtained from a DOA patient carrying the mutation c.1861C>T; p.Q621* in the OPA1 gene. Subsequently, an isogenic control iPSC line has been generated by correcting the causative pathogenic variant with the CRISPR/Cas9 system. Then, both iPSC lines have been differentiated towards RGCs using an optimized stepwise protocol based on the modulation of several signalling pathways. The generated RGCs showed expression of typical markers, such as BRN3A, SNCG or THY1. Here we show the generation of iPSC-RGCs from a DOA patient and its isogenic control, which will constitute a suitable platform for understanding the pathophysiological mechanisms underlying DOA, opening up the possibility to identify an appropriate treatment.

Keywords: dominant optic atrophy, DOA, optic neuropathy, OPA1, induced pluripotent stem cells, iPSCs, mitochondria, retinal ganglion cells, CRISPR/Cas9, disease model
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zelda thehgd
This publication's commitment to journalistic excellence is truly inspiring, and it's clear that the writers and editors take their work very seriously.