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The role of complement in retinal ganglion cell loss in glaucoma

Glaucoma is an umbrella term for a number of related optic neuropathies which have the common pathology of a progressive, irreversible vision loss associated with atrophy of retinal ganglion cells. Together, the various forms of glaucoma constitute the second leading cause of vision loss in the developed world. Current therapies for the treatment of glaucoma focus on alleviating the primary risk factor, an elevation in intraocular pressure. These treatments are effective at mitigating the progression of vision loss however they cannot recover vision and do not completely halt vision loss, limiting their use as treatments. To better understand the biology underlying the loss of retinal ganglion cells in glaucoma, I have examined the role of complement in retinal ganglion cell loss. Complement is a network of cross-reacting serine proteases which form part of the humoral immune system and are primarily responsible for clearance of apoptotic cells and defence against pathogens. To understand the role played by complement in glaucoma I used an inducible model of glaucoma to establish the complement activation occurs in the glaucomatous retina. I then used the inhibitor of the classical complement cascade, C1 inhibitor to protect the dendrites and cell bodies of retinal ganglion cells and found that this protection did not prevent axonal degeneration. Using in vitro and in vivo animal models of complement deficiency I established that deficiency in complement components C3 and C6 which are further down the cascade, exacerbates damage suffered in hypertensive glaucoma. This study adds to the existing evidence that the role of complement in central nervous system degeneration is a complex, multifactorial process, with elements of the complement system being variously protective and damaging. It does, however, add hope to the prospect of developing a treatment for glaucomatous optic neuropathy based on manipulation of the complement system.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:610983
Date January 2012
CreatorsCross, Stephen Daniel
PublisherCardiff University
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://orca.cf.ac.uk/60068/

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