Indiana University-Purdue University Indianapolis (IUPUI) / Human pluripotent stem cells (hPSCs) have the ability to self renew indefinitely
while maintaining their pluripotency, allowing for the study of virtually any human
cell type in a dish. The focus of the current study was the differentiation of hPSCs
to retinal ganglion cells (RGCs), the primary cell type affected in optic neuropathies.
hPSCs were induced to become retinal cells using a stepwise differentiation protocol
that allowed for formation of optic vesicle (OV)-like structures. Enrichment of OV
like structures allowed for the definitive identification of RGCs. RGCs displayed the
proper temporal, spatial, and phenotypic characteristics of RGCs developing in vivo.
To test the ability of hPSC-RGCs to serve as a disease model, lines were generated
from a patient with an E50K mutation in the Optineurin gene, causative for normal
tension primary open angle glaucoma. E50K RGCs displayed significantly higher
levels of apoptosis compared to a control lines. Apoptosis was reduced with exposure
to neuroprotective factors. Lastly, hPSC-derived RGCs were studied for their ability
to develop functional features possessed by mature in vivo RGCs. hPSC-derived
RGCs displayed a few immature functional features and as such, strategies in which
to expedite synaptogenesis using hPSC-derived astrocytes were explored. Astrocyte
and RGG co-cultures displayed expedited synaptic and functional maturation, more
closely resembling mature in vivo RGCs. Taken together, the results of this study
have important implications for the study of RGC development and by extension, the
advancement of translational therapies for optic neuropathies.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/16974 |
| Date | January 2018 |
| Creators | Ohlemacher, Sarah K. |
| Contributors | Meyer, Jason S. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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