Dr Terence Smith
Research Topics and Related Projects:
My current research is centred on a potential antioxidant therapy for dominant optic atrophy patients. It is a translational project and I am using a model of Opa1 to conduct the trial. Mutations in the Opa1 gene were uncovered as segregating with affected patients, and otherwise would encode a mitochondrial membrane fusion protein. By virtue of its involvement in the changing dynamics of mitochondrial reticular networks, it acts to maintain an efficient electron transport chain and steady ATP energy output, as well as regulating cytochrome c release and apoptosis. Efforts to ameliorate these disturbances in affected patients include the use of electron-shuttling factors to shore-up mitochondrial instability and is the concept behind the trial. I am imaging the dendritic tree of retinal ganglion cells as one read-out of this work, which involves making the most of the confocal and imaging facilities found here in the School of Optometry and Vision Sciences.
In dominant optic atrophy the optic disc (in yellow) undergoes retinal ganglion cell loss and atrophy. Patients have a mutation in the Opa1 gene that is responsible for their clinical condition.
The methods I use to achieve my research goals include dissection of the retina, shown here in flat-mount. Retinas are then processed for imaging of dendritic morphology by use of a Helios® Gene Gun system.
A single retinal ganglion cell labelled with DiI that clearly shows the degree of dendritic arborisation. These images are taken from confocal optical sections.