Astrocytes modulate neurodegenerative phenotypes associated with glaucoma in OPTN(E50K) human stem cell-derived retinal ganglion cells

dc.contributor.authorGomes, Cátia
dc.contributor.authorVanderWall, Kirstin B.
dc.contributor.authorPan, Yanling
dc.contributor.authorLu, Xiaoyu
dc.contributor.authorLavekar, Sailee S.
dc.contributor.authorHuang, Kang-Chieh
dc.contributor.authorFligor, Clarisse M.
dc.contributor.authorHarkin, Jade
dc.contributor.authorZhang, Chi
dc.contributor.authorCummins, Theodore R.
dc.contributor.authorMeyer, Jason S.
dc.contributor.departmentMedical and Molecular Genetics, School of Medicine
dc.date.accessioned2023-07-26T16:46:41Z
dc.date.available2023-07-26T16:46:41Z
dc.date.issued2022
dc.description.abstractAlthough the degeneration of retinal ganglion cells (RGCs) is a primary characteristic of glaucoma, astrocytes also contribute to their neurodegeneration in disease states. Although studies often explore cell-autonomous aspects of RGC neurodegeneration, a more comprehensive model of glaucoma should take into consideration interactions between astrocytes and RGCs. To explore this concept, RGCs and astrocytes were differentiated from human pluripotent stem cells (hPSCs) with a glaucoma-associated OPTN(E50K) mutation along with corresponding isogenic controls. Initial results indicated significant changes in OPTN(E50K) astrocytes, including evidence of autophagy dysfunction. Subsequently, co-culture experiments demonstrated that OPTN(E50K) astrocytes led to neurodegenerative properties in otherwise healthy RGCs, while healthy astrocytes rescued some neurodegenerative features in OPTN(E50K) RGCs. These results are the first to identify disease phenotypes in OPTN(E50K) astrocytes, including how their modulation of RGCs is affected. Moreover, these results support the concept that astrocytes could offer a promising target for therapeutic intervention in glaucoma.
dc.eprint.versionFinal published version
dc.identifier.citationGomes C, VanderWall KB, Pan Y, et al. Astrocytes modulate neurodegenerative phenotypes associated with glaucoma in OPTN(E50K) human stem cell-derived retinal ganglion cells. Stem Cell Reports. 2022;17(7):1636-1649. doi:10.1016/j.stemcr.2022.05.006
dc.identifier.urihttps://hdl.handle.net/1805/34579
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1016/j.stemcr.2022.05.006
dc.relation.journalStem Cell Reports
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcePMC
dc.subjectStem cell
dc.subjectRetina
dc.subjectRetinal ganglion cell
dc.subjectAstrocyte
dc.subjectNeurodegeneration
dc.subjectGlaucoma
dc.subjectAutophagy
dc.titleAstrocytes modulate neurodegenerative phenotypes associated with glaucoma in OPTN(E50K) human stem cell-derived retinal ganglion cells
dc.typeArticle
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