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Title: Mouse models of intra-ocular pressure, with applications to glaucoma
Author: Boussommier-Calleja, Alexandra
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Glaucoma is the second most common cause of blindness worldwide and is often associated with an increased intraocular pressure (IOP). IOP is determined by the dynamics of aqueous humour, the liquid filling the anterior segment of the eye. In primary-open angle glaucoma, the elevated IOP is caused by a decreased outflow facility of aqueous humour through the conventional pathway (decreased conventional facility, C). Existing glaucoma therapies aim to lower IOP, but remain inefficient because they fail to target C. As a result, there is growing interest in using the mouse to unravel the mechanisms controlling C. The mouse is a particularly powerful model because it can be routinely manipulated genetically, thereby giving insight into molecules and genes involved in determining C. However, it is still not clear whether mice are suitable surrogates for studying human C. To fill this gap, we aim to demonstrate that the mouse is a suitable model for human IOP regulation, and to then use this model to investigate key processes in IOP regulation. To achieve this aim we used an existing perfusion system to measure C in enucleated mouse eyes. First, we improved the perfusion system by including hydration and temperature control to better mimic in vivo perfusions. Secondly, selected receptor-mediated drugs were found to have similar effects on C in mice as they did in past human studies. Finally, we show, amongst other studies, anti-metabolic agents decreased C, suggesting aqueous humour outflow is metabolic dependent. We conclude that the mouse is a valid model for studying human conventional facility, yielding novel insight into the mechanisms controlling conventional facility. Importantly, this will help the design of novel efficient anti-glaucoma treatments. Notably, this project will have brought fundamental insight into mouse eye perfusions, thereby consolidating the technique for future studies.
Supervisor: Overby, Darryl ; Ethier, Ross Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available