Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.690945
Title: Retinal degeneration and remodelling in experimental glaucoma
Author: Tribble, James R.
ISNI:       0000 0004 5916 1693
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2016
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.690945  DOI: Not available
Keywords: RE Ophthalmology
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