The Role of Biomechanics and Mechanobiology in Diseases of the Posterior Eye
Glaucoma is a leading cause of blindness worldwide, affecting approximately 70 million people. Glaucoma is a group of eye conditions that cause damage to the optic nerves with progressive loss of vision. The only proven method to treat most patients with glaucoma is to reduce intraocular pressure (IOP). It is believed that a decrease in IOP alleviates the excessive mechanical strain on the retinal ganglion cells (RGCs) within the optic nerve head (ONH). Elevated IOP deforms the ONH tissues, a deformation which is thought to predispose resident astrocytes to transition from a normal functional cell to a diseased state. Under healthy conditions, astrocytes maintain the extracellular matrix (ECM) within the ONH and provide neurotransmitter support to RGC axons. However, this transition, or activation, of astrocytes is believed to contribute to RGC death, resulting in vision loss. The details of this ONH astrocyte activation in response to the increased IOP is unclear.
ONH astrocytes are subjected to different modes of mechanical strain during elevated IOP. However, computational modelling demonstrated that compression is the major strain applied to the ONH during elevated IOP. Therefore, understanding when and how ONH astrocytes activate due to this compressive mechanical strain is imperative to furthering our knowledge of the cellular mechanisms behind RGC dysfunction and death. While 2D culture models have revealed important information, they do not accurately mimic the 3D physiological environment of the ONH, and typically have increased levels of astrocyte reactivity in the absence of mechanostimulation. However, cells can better mimic their physiological form and function when placed in a 3D culture environment. In order to mimic the in vivo environment of the ONH, and isolate the effect of compressive mechanical strain due to elevated IOP, a 3D in vitro system has been developed in this study.
In this presentation, a 3D system will be presented and shown how it is a step toward a more representative model for studying astrocyte activation. Through the development of novel protocols for gelatinase Zymography, flow cytometry, and Western blotting, it will be shown that astrocytes respond to glaucomatous levels of mechanical stimulation by altering cell orientation and protease activity, and increase expression of key activation markers compared to astrocytes in static control gels. This work is a step toward understanding the role of mechanics and astrocyte activation in the progression of glaucoma.
ABOUT THE PRESENTER
Dr Mulvihill recently returned to the University of Limerick from his post-doctoral work at Georgia Institute of Technology to take up a position as a Lecturer in Biomedical Engineering within the School of Engineering. Dr Mulvihill completed a degree in Mechanical Engineering in the University of Limerick in 2009, and was awarded the Innovative Student Engineer of the Year, 2009 by Engineers Ireland and Siemens for his final year project work. He was awarded an IRCSET scholarship to undertake a PhD in Biomedical Engineering in UL where he graduated in 2013. His PhD research focussed on the characterisation of mechanical, structural and biological of diseased cardiovascular tissue. Following the completion of his research in UL, Dr Mulvihill joined the Dr Bruce Murphy group at Trinity College Dublin. While in TCD, he was involved in the EU FP7 funded AMCARE project (€8.7M), to develop regenerative therapies that aim to use biomaterials to deliver cells or growth factors to the heart to treat myocardial infarction. In 2014, Dr Mulvihill was awarded the Marie Curie co-funded ELEVATE fellowship. He carried out his post-doctoral research in the Professor Ross Ethier lab in Georgia Institute of Technology. Here Dr Mulvihill conducted research in 3D cell culture and astrocyte mechanobiology, particularly the role of astrocytes in the progression of glaucoma. He is co-author on 15 scientific papers which are currently cited 159 times and has a h-index of 7.
DATE: Friday, 9 December 2016
VENUE: MSG-024 MSSI Building Extension
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