Astrocytes in Focus: Imaging-Based Insights into the Optic Nerve Head Neurovascular Unit in the Context of Health and GlaucomaWaxman, Susannah (2024) Astrocytes in Focus: Imaging-Based Insights into the Optic Nerve Head Neurovascular Unit in the Context of Health and Glaucoma. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractGlaucoma is a leading cause of irreversible blindness worldwide. Injury to retinal ganglion cells (RGCs), the neurons which bridge the eye and rest of the brain, can lead to the progressive optic neuropathy and resulting vision loss characteristic of the disease. The optic nerve head (ONH), the anatomic site where all RGC axons converge to exit the eye, is an initial site of injury to these axons in glaucoma. Glaucomatous injury and consequent neuropathy are often associated with elevated intraocular pressure (IOP). IOP is currently the only modifiable risk factor for glaucoma, with available treatments designed to control this pressure. Even with treatment, over half of glaucoma patients continue to experience progressive neurodegeneration. This points to a critical gap in our knowledge of both normal and glaucomatous physiology. To address this knowledge gap, I investigated ONH elements likely to play roles in the initiation and progression of glaucoma which can be influenced by factors outside of IOP. As dysfunction of neurovascular physiology has been strongly implicated in glaucoma, specific focus in this work is placed on elements of the neurovascular unit, including blood vessels, pericytes, and astrocytes. Additional emphasis is placed on furthering our understanding of these elements in the collagenous lamina cribrosa (LC), an anatomic structure present within the ONH of humans and other large mammals but not in a common research model, the mouse. In this work, I provide key insights into 1) the role of intracranial pressure (ICP) and its interaction with IOP in mechanical deformation of the ONH, 2) the organization of vasculature and collagen beams across the LC, 3) the roles of pericytes in health and disease of the ONH, and 4) the unique structure and potential for function of astrocytes in the LC. Additionally, I demonstrate innovative strategies to investigate the ONH. These strategies can be built upon to better understand this complex tissue in health and disease, and in turn, help address the profound burden of glaucoma. Share
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