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UCP2-Dependent Changes in Mitochondr...

Hass, Daniel T.

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UCP2-Dependent Changes in Mitochondrial Dynamics Protect the Retina from Glaucoma.

Record Type:	Electronic resources : Monograph/item
Title/Author:	UCP2-Dependent Changes in Mitochondrial Dynamics Protect the Retina from Glaucoma./
Author:	Hass, Daniel T.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	132 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Contained By:	Dissertations Abstracts International80-12B.
Subject:	Neurosciences. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13917913
ISBN:	9781392318461

UCP2-Dependent Changes in Mitochondrial Dynamics Protect the Retina from Glaucoma.
Hass, Daniel T.

UCP2-Dependent Changes in Mitochondrial Dynamics Protect the Retina from Glaucoma. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 132 p.

Source: Dissertations Abstracts International, Volume: 80-12, Section: B.

Thesis (Ph.D.)--The Pennsylvania State University, 2019.

Glaucoma is a neurodegenerative disorder characterized by mitochondrial dysfunction and an increase in oxidative damage, leading to progressive retinal ganglion cell (RGC) degeneration. The oxidative status of RGCs is regulated intrinsically and also extrinsically by retinal glia. The mitochondrial uncoupling protein 2 (UCP2) relieves oxidative and neuronal damage in a variety of neurodegenerative disease models. However, the impact of Ucp2 on cell survival during sub-acute and chronic neurodegenerative conditions is not yet clear. Herein, we test the hypothesis that increased Ucp2 expression will improve retinal ganglion cell survival in a mouse model of glaucoma. We show that increasing retinal ganglion cell but not glial Ucp2 expression in transgenic animals decreases glaucomatous RGC death, but also that the PPAR-γ agonist rosiglitazone, an endogenous transcriptional activator of Ucp2, does not significantly alter RGC loss during glaucoma, suggesting differences in regulation of the protective transgene and the endogenous gene. We additionally hypothesized that deletion of Ucp2 in either RGCs or retinal glia would increase retinal damage and retinal ganglion cell death in a mouse model of glaucoma. Paradoxically, we found the reverse, and deletion of mitochondrial UCP2 decreased oxidative protein modification and reduced retinal ganglion cell death in male and female mice. This paradox was resolved after finding that Ucp2 deletion also increased levels of mitophagy in cell culture and retinal tissue. Together, our data show that both Ucp2 deletion and elevated Ucp2 expression facilitate increased mitochondrial function, either by reducing the generation of reactive oxygen species or by improving quality control, though transcriptional activation alone is insufficient to elicit this neuroprotective effect, motivating further research into the post-transcriptional regulation of Ucp2. These data support a model whereby certain forms of increased Ucp2 expression mediate neuroprotection during long-term oxidative stress, and may provide a therapeutic avenue for other chronic neurodegenerative conditions.

ISBN: 9781392318461Subjects--Topical Terms:

588700
Neurosciences.

UCP2-Dependent Changes in Mitochondrial Dynamics Protect the Retina from Glaucoma.
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