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Optic Nerve Head Molecular and Cellu...

Oikawa, Kazuya.

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Optic Nerve Head Molecular and Cellular Pathology in a Spontaneous Large Animal Model of Glaucoma.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Optic Nerve Head Molecular and Cellular Pathology in a Spontaneous Large Animal Model of Glaucoma./
作者:	Oikawa, Kazuya.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	249 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-10, Section: B.
Contained By:	Dissertations Abstracts International82-10B.
標題:	Ophthalmology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28321698
ISBN:	9798597069111

Optic Nerve Head Molecular and Cellular Pathology in a Spontaneous Large Animal Model of Glaucoma.
Oikawa, Kazuya.

Optic Nerve Head Molecular and Cellular Pathology in a Spontaneous Large Animal Model of Glaucoma. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 249 p.

Source: Dissertations Abstracts International, Volume: 82-10, Section: B.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2021.

This item must not be sold to any third party vendors.

Glaucoma is a common neurodegenerative disease leading to vision loss, which is characterized by progressive loss of retinal ganglion cells and their axons. Intraocular pressure (IOP) is a major risk factor, in which optic nerve insult initially occurs at the optic nerve head (ONH). Current treatments for glaucoma hinge on IOP-lowering therapy but progressive vision loss still occurs in a significant proportion of patients. Pathological mechanisms involved in axon damage at the ONH are poorly understood, presenting a major obstacle to development of neuroprotective therapies. The objective of my work is to identify cellular and molecular mechanisms, as future targets for development of novel neuroprotective therapies, by dissecting the pathobiology of glaucoma in a unique, highly-relevant genetic large animal model that has ONH structure that more closely resembles that of humans than the ONH structure of widely-used rodent models. The feline ONH was characterized by a variety of labeling and microscopy techniques, which revealed that the feline ONH has similar microanatomy to that of humans. Gene expression profiling of feline ONH tissues identified cell proliferation and inflammatory responses in early glaucoma, prior to morphologically detectable axon loss. Cell-type specific analyses identified proliferation of myeloid and oligodendrocyte precursor cells in early-stage, but not in later, chronic stages of glaucoma, suggesting cell-type- and disease-stage-specific glaucoma pathobiology. Neuroinflammation and myeloid cell activation in glaucoma were further characterized within the context of complex ONH microanatomy. Both IOP and axon damage contribute to ONH myeloid cell activation. In situ hybridization identified a small subset of ONH myeloid cells expressing pro-inflammatory genes. Additionally, results identified evidence of ONH monocyte infiltration in glaucoma. The myeloid cell molecular signatures differed significantly between ONH sub-compartments in normal and glaucoma. These results highlighted key roles of ONH myeloid cell populations in neuroinflammation and emphasize the spatiotemporal complexity of myeloid cell pathobiology in glaucoma. In summary, this work provides comprehensive insights into ONH cellular and molecular pathology in a translationally-relevant, spontaneous glaucoma model. These insights will provide a foundation for future studies that will target neuroinflammation in the development of potential neuroprotective therapies, to prevent progressive vision loss in glaucoma.

ISBN: 9798597069111Subjects--Topical Terms:

862704
Ophthalmology.
Subjects--Index Terms:

Cat's eyes

Optic Nerve Head Molecular and Cellular Pathology in a Spontaneous Large Animal Model of Glaucoma.
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