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@ARTICLE{Vlkner:157808,
author = {Völkner, Manuela and Kurth, Thomas and Schor, Jana and
Ebner, Lynn J A and Bardtke, Lara and Kavak, Cagri and
Hackermüller, Jörg and Karl, Mike Oliver},
title = {{M}ouse {R}etinal {O}rganoid {G}rowth and {M}aintenance in
{L}onger-{T}erm {C}ulture.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
issn = {2296-634X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DZNE-2021-01265},
pages = {645704},
year = {2021},
note = {CC BY},
abstract = {Using retinal organoid systems, organ-like 3D tissues,
relies implicitly on their robustness. However, essential
key parameters, particularly retinal growth and longer-term
culture, are still insufficiently defined. Here, we
hypothesize that a previously optimized protocol for high
yield of evenly-sized mouse retinal organoids with low
variability facilitates assessment of such parameters. We
demonstrate that these organoids reliably complete
retinogenesis, and can be maintained at least up to 60 days
in culture. During this time, the organoids continue to
mature on a molecular and (ultra)structural level: They
develop photoreceptor outer segments and synapses,
transiently maintain its cell composition for about 5-10
days after completing retinogenesis, and subsequently
develop pathologic changes - mainly of the inner but also
outer retina and reactive gliosis. To test whether this
organoid system provides experimental access to the retina
during and upon completion of development, we defined and
stimulated organoid growth by activating sonic hedgehog
signaling, which in patients and mice in vivo with a
congenital defect leads to enlarged eyes. Here, a sonic
hedgehog signaling activator increased retinal epithelia
length in the organoid system when applied during but not
after completion of development. This experimentally
supports organoid maturation, stability, and experimental
reproducibility in this organoid system, and provides a
potential enlarged retina pathology model, as well as a
protocol for producing larger organoids. Together, our study
advances the understanding of retinal growth, maturation,
and maintenance, and further optimizes the organoid system
for future utilization.},
keywords = {development (Other) / gliosis (Other) / growth (Other) /
maturation (Other) / mouse (Other) / organoid (Other) /
retina (Other) / sonic hedgehog (Other)},
cin = {AG Karl},
ddc = {570},
cid = {I:(DE-2719)1710004},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33996806},
pmc = {pmc:PMC8114082},
doi = {10.3389/fcell.2021.645704},
url = {https://pub.dzne.de/record/157808},
}