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The role of innate immune activation in experimental glaucoma

Kokkali, Eirini 2022. The role of innate immune activation in experimental glaucoma. PhD Thesis, Cardiff University.
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Glaucoma is the leading cause of irreversible blindness worldwide. It is characterised by progressive degeneration and loss of retinal ganglion cells (RGCs) and their axons. Increasing amount of evidence indicates that neuroinflammation plays a role in glaucoma and other neurodegenerative diseases, however, its contribution in disease pathophysiology is not clear. Targeting components of the immune system, particularly the complement system, has been proposed as a potential treatment strategy for glaucoma. This thesis investigates the effect of systemic innate immune activation on RGC degeneration, in a rat experimental glaucoma model. Ocular hypertension (OHT) is one of the main risk factors for glaucoma, so this thesis uses a model of induced OHT to mimic glaucoma, and systemic lipopolysaccharide (LPS) administration to induce innate immune activation. Morphological analysis of RGC dendrites and functional assessment of the retina, showed that OHT induced dendritic atrophy and functional deficits in the retina. However, innate immune activation did not further exacerbate RGC degeneration in this model and was associated with protection of RGC dendrites, while intravitreal inhibition of the classical pathway of the complement system did not have a significant effect on the progress of RGC degeneration. In addition, microglial activation was observed in OHT eyes and interestingly in contralateral normotensive (NT) eyes. Overall, this thesis demonstrates the need for further research to understand the multifaceted role of immune activation in glaucoma and other neurodegenerative diseases. It also warrants for caution in the use of NT contralateral eyes as controls in ophthalmic research.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: glaucoma, experimental glaucoma, retinal ganglion cells, neurodegeneration, inflammation, microglia, complement system
Date of First Compliant Deposit: 10 March 2023
Last Modified: 09 Mar 2024 02:30

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