Unknown

Dataset Information

0

Retinal Ganglion Cells With a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids.


ABSTRACT: Retinal ganglion cells (RGCs) serve as the connection between the eye and the brain, with this connection disrupted in glaucoma. Numerous cellular mechanisms have been associated with glaucomatous neurodegeneration, and useful cellular models of glaucoma allow for the precise analysis of degenerative phenotypes. Human pluripotent stem cells (hPSCs) serve as powerful tools for studying human disease, particularly cellular mechanisms underlying neurodegeneration. Thus, efforts focused upon hPSCs with an E50K mutation in the Optineurin (OPTN) gene, a leading cause of inherited forms of glaucoma. CRISPR/Cas9 gene editing introduced the OPTN(E50K) mutation into existing lines of hPSCs, as well as generating isogenic controls from patient-derived lines. RGCs differentiated from OPTN(E50K) hPSCs exhibited numerous neurodegenerative deficits, including neurite retraction, autophagy dysfunction, apoptosis, and increased excitability. These results demonstrate the utility of OPTN(E50K) RGCs as an in vitro model of neurodegeneration, with the opportunity to develop novel therapeutic approaches for glaucoma.

SUBMITTER: VanderWall KB 

PROVIDER: S-EPMC7363877 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Retinal Ganglion Cells With a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids.

VanderWall Kirstin B KB   Huang Kang-Chieh KC   Pan Yanling Y   Lavekar Sailee S SS   Fligor Clarisse M CM   Allsop Anna R AR   Lentsch Kelly A KA   Dang Pengtao P   Zhang Chi C   Tseng Henry C HC   Cummins Theodore R TR   Meyer Jason S JS  

Stem cell reports 20200611 1


Retinal ganglion cells (RGCs) serve as the connection between the eye and the brain, with this connection disrupted in glaucoma. Numerous cellular mechanisms have been associated with glaucomatous neurodegeneration, and useful cellular models of glaucoma allow for the precise analysis of degenerative phenotypes. Human pluripotent stem cells (hPSCs) serve as powerful tools for studying human disease, particularly cellular mechanisms underlying neurodegeneration. Thus, efforts focused upon hPSCs w  ...[more]

Similar Datasets

| S-EPMC9287669 | biostudies-literature
2020-02-11 | GSE145069 | GEO
| S-EPMC3994150 | biostudies-other
| S-EPMC5031982 | biostudies-literature
| S-EPMC8203676 | biostudies-literature
| S-EPMC6162218 | biostudies-literature
| S-EPMC7259937 | biostudies-literature
| S-EPMC3627667 | biostudies-literature
2022-08-16 | GSE192509 | GEO
| S-EPMC8844082 | biostudies-literature