The retinal ganglion cell axonal cytoskeleton and its significance in glaucoma and retinal disease pathogenesis

Chandrakumar Balaratnasingam

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated abstract] The retinal ganglion cell (RGC) axon demonstrates an array of unique structural adaptations, critical to its function, and arguably serves the most important role in mammalian vision. RGC axonal disease continues to be a major cause of visual morbidity globally. Glaucoma is the most common form of RGC axon disease and accounts for 14% of blindness in the western world. Glaucomatous optic neuropathy is consequent upon loss of RGC axons and classically manifests as optic disk cupping. Although it is generally agreed that the site of greatest axonal damage in glaucoma is the optic nerve head, the complex sequence of cellular events between axonal injury and RGC death have not been clearly delineated. As such, there continues to be considerable debate concerning the causeconsequence relationships in glaucoma pathogenesis. This thesis provides new, detailed information concerning the role of cytoskeleton proteins within the retinal and optic nerve head compartments of the RGC axon in physiological conditions and in disease. Investigations are performed, utilizing a porcine experimental model, to delineate the time-dependent behaviour of RGC axonal cytoskeleton proteins following IOP-, ischemia- and axotomy-induced insults. The chronology of axonal cytoskeleton protein alterations with respect to astrocyte, mitochondrial, cytochrome c oxidase and axonal transport changes have been addressed in order that pathogenic inter-relationships in glaucoma biology could be better understood. Comparisons of cytoskeleton and astrocyte changes between the various forms of RGC axonal injury also provide insights into vascular and mechanical components that are involved in glaucoma pathogenesis. Additionally, the role of pia mater in protecting RGC axons from injury is explored.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2011

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