Stem cells as neuroprotective vectors for retinal disease

dc.contributor.advisor Donald S. Sakaguchi Harper, Matthew
dc.contributor.department Theses & dissertations (Interdisciplinary) 2018-08-22T21:48:14.000 2020-06-30T07:45:49Z 2020-06-30T07:45:49Z Mon Jan 01 00:00:00 UTC 2007 2007-01-01
dc.description.abstract <p>Glaucoma is a family of neurodegenerative diseases of the eye which results in retinal ganglion cell (RGC) death, optic nerve atrophy, and eventual blindness if left untreated. A risk factor typically associated with glaucoma is elevated intraocular pressure (IOP), which most treatments are currently designed to lower. While beneficial in most patients, these therapies do not provide neuroprotection to retinal ganglion cells. The studies included in this dissertation present a potential alternative treatment for glaucoma, which provides neuroprotection to RGCs in a rodent model of glaucoma.;In these studies mesenchymal stem cells (MSCs) were used as cellular vehicles to deliver neuroprotective substances to compromised retinas. Lentiviral vectors were used to engineer MSCs to secrete the neuroprotective protein brain-derived neurotrophic factor (BDNF, BDNF-MSCs). An additional line of control MSCs was engineered to produce green fluorescent protein (GFP, GFP-MSCs). We examined the neuroprotective capacity of BDNF-MSCs using in vitro, and in vivo models of glaucoma, as compared to GFP-MSCs.;A transformed line of retinal ganglion cells, the RGC-5s, were used to model glaucoma in vitro following differentiation with the general kinase inhibitor staurosporine. We have demonstrated a significant loss of RGC-5s following treatment with cellular stressors that have been implicated in RGC death in glaucoma, glutamate and hydrogen peroxide (H2O 2), as compared to vehicle treated controls. This cell loss can be attenuated when RGC-5s are cultured in the presence BDNF-MSCs, but not GFP-MSCs.;The neuroprotective capacity of BDNF-MSCs was also examined in vivo. Engineered MSCs were transplanted into the rat model of chronic ocular hypertension (COH). It was revealed that BDNF-MSCs, but not GFP-MSCs, were able to preserve retinal function and architecture, including neuroprotection of RGCs, following transplant.;These studies are the first to describe protection of retinal architecture and function in a model of glaucoma using MSCs to deliver a neuroprotective protein. Additionally, these studies pave the way toward developing treatments for human glaucoma that are compatible with existing treatments.</p>
dc.format.mimetype application/pdf
dc.identifier archive/
dc.identifier.articleid 16605
dc.identifier.contextkey 7037562
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath rtd/15606
dc.language.iso en
dc.source.bitstream archive/|||Fri Jan 14 20:43:54 UTC 2022
dc.subject.disciplines Neuroscience and Neurobiology
dc.subject.disciplines Neurosciences
dc.subject.disciplines Ophthalmology
dc.subject.keywords Genetics
dc.subject.keywords development and cell biology;Neuroscience
dc.title Stem cells as neuroprotective vectors for retinal disease
dc.type article
dc.type.genre dissertation
dspace.entity.type Publication Neuroscience dissertation Doctor of Philosophy
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