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Retinal degeneration and remodelling in experimental glaucoma

Tribble, James R. 2016. Retinal degeneration and remodelling in experimental glaucoma. PhD Thesis, Cardiff University.
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Abstract

Glaucoma is an optic neuropathy characterised by the loss of retinal ganglion cells (RGC). Dendritic atrophy occurs early in the disease, prior to soma and axonal degeneration. RGCs exhibit reduced branching density and dendritic field size. This thesis seeks to further characterise dendritic atrophy in glaucoma in the context of two external factors that may contribute to the disease pathology – immune system effects mediated via complement and the influence of the perineuronal net (PNN), a specialised extracellular matrix that surrounds RGCs. RGC morphology was investigated in a rat bead model of experimental glaucoma using ballistic labelling techniques; morphological changes were related to synaptic loss and PNN composition using immunohistochemistry. A model was derived for the classification of diseased RGCs in order to prevent labelling bias in subsequent investigations. The immune system was modulated using a complement inhibitor (using a transgenic mouse and pharmacological agent in rats) and PNNs disrupted using the bacterial enzyme Chondroitinase ABC. Experimental glaucoma caused significant dendritic loss, with partial protection conferred by both complement inhibition and PNN digestion. Analysis of retinal sections also revealed partial protection of synapses. PNNs did not show any changes in their composition in the rat in experimental glaucoma but human glaucoma eyes showed increased glycosaminoglycan sulphation in the RGC layer which was correlated with visual deficit. Manipulation of the RGC external environment therefore proved successful in protecting from dendritic atrophy.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: glaucoma, retina, ganglion cell, complement, perineuronal ne
Date of First Compliant Deposit: 9 August 2016
Last Modified: 21 Aug 2019 02:14
URI: http://orca.cf.ac.uk/id/eprint/93668

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