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Title: The role of glial cells in a mouse model of inherited retinal dystrophies
Authors: Chen, Yingdi
Issue Date: 2019
Publisher: Newcastle University
Abstract: Inherited retinal dystrophies are a heterogeneous group of degenerative disorders characterised by genetically induced photoreceptor loss, leading to vision loss. Despite their genetic and clinical complexity, most inherited retinal dystrophies follow a common pathological pathway characterised by photoreceptor death and glial activation. Although glial activation has been widely reported in retinal degenerative diseases, the underlying mechanisms involved in the neuron-glial interaction and the role of glial activation in the degenerative process remain unclear. In this thesis, investigation of the relationship between glial activation and photoreceptor loss was conducted using a mouse model of Leber congenital amaurosis, the cone-rod homeobox (Crx) knockout mouse. The first part of the study aimed to establish a framework of photoreceptor death and glial activity during the degeneration process. Thinning of the outer nuclear layer suggested that, in the Crx retina, photoreceptors do not die at a constant rate, but occurred mostly during two rapid degeneration periods. Analysis of the glial activities revealed that changes in both microglial activity and Müller activity are highly correlated with the two waves of photoreceptor death. The second part of the study investigated the role of microglial activation in the photoreceptor degeneration process using a microglial inhibitor, Neurostatin. The results suggest that microglial activation accelerates photoreceptor loss and that inhibiting microglial activity could slow the process down. These findings demonstrate a spatiotemporal relationship between microglial activity and photoreceptor degeneration, indicating a possible contribution of microglial cells towards photoreceptor loss. Taken together, these observations suggest that microglial inhibition is a promising strategy for visual restoration in retinal degeneration and provides important insights for future studies on microglial activation in retinal diseases.
Description: PhD Thesis
Appears in Collections:Institute of Neuroscience

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