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Download StatisticsThomas, Chloe (2019). Characterisation of the mechanisms of retinal ganglion cell death in direct and indirect traumaticoptic neuropathy. University of Birmingham. Ph.D.
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Thomas2019PhD.pdf
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Abstract
Retinal ganglion cells (RGCs) exist in the retina and their axons form the optic nerve (ON), the main connection from the eye to the brain. RGCs are post-mitotic neurons, therefore, if these cells degenerate by injury or disease, they are not endogenously replaced, leading to irreversible blindness. Military and civilian populations can be injured by explosive blasts during conflict or terrorist attacks, which can cause traumatic ocular injuries. Primary blast injuries (PBI) are caused by the primary blast wave (a rapid increase in atmospheric pressure). In closed-space explosions the blast wave can propagate off surfaces and cause repeated impact. Secondary blast injuries occur from blunt force by debris carried in the blast wind. There are no effective treatments and an urgent need for therapeutic interventions to help preserve vision.
This thesis investigates cell death mechanisms in RGCs using in vivo rodent models of repeated PBI (rPBI) and blunt ocular injury. Apoptotic caspase-2-dependent and necroptotic RGC death is likely to occur after blunt ocular injury in a site-specific manner. Caspase-2 knockdown using a small interfering RNA (siRNA) provided some structural and functional protection at the periphery of the impact site, with pharmacological inhibition of necroptosis using Necrostatin-1s providing some RGC protection, likely at the impact site centre. Furthermore, performing intravitreal injections in close proximity to the time of rPBI caused exacerbated RGC death and vitreal inflammation, which was absent when treatment was given before the injury.
Collectively, this research provides novel insights into cell death signalling in traumatic ocular injuries caused by primary blast wave exposure and blunt impact, and into therapeutics which could preserve vision in victims injured during terrorist attacks or war.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (former) > College of Medical & Dental Sciences | |||||||||
| School or Department: | Institute of Inflammation and Ageing | |||||||||
| Funders: | Other | |||||||||
| Other Funders: | Fight for Sight | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/9994 |
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