Vision loss and mitochondria - the energy producers of cells 

The majority of patients with DOA carry harmful mutations in the OPA1 gene that encodes an important protein found in mitochondria - the energy factories in our cells. This project is focused on investigating how OPA1 mutations affect mitochondria and contribute to nerve cell death and sight loss.

Dr Joshua Harvey, a specialist registrar, has embedded research into his training career to date, including undertaking a project looking at a Parkinson’s disease model during his intercalated research degree. Now, with a Moorfields Eye Charity research training fellowship Joshua will have the opportunity and support to undertake a three year project towards a PhD. He will also have protected time to continue his specialist training in neuro-ophthalmology – thereby ensuring his clinical training is not interrupted during this time.

The aim of this project is to investigate the mitochondrial dysfunction in retinal ganglion cells (RGCs) carrying a range of OPA1 mutations identified in DOA patients. Joshua will measure energy production, the life cycle and transport of mitochondria with OPA1 mutations. He will also investigate the effects of these mutations in non-ocular cell types, comparing RGCs with skin cells and other nerve cells.

This project aims to increase the understanding of how different OPA1 mutations result in abnormal cell function. This research ultimately has the goal to provide better insight into why RGCs are preferentially affected in DOA. Also, why some patients with DOA develop non-ocular symptoms, such as peripheral nerve problems – known as DOA plus syndrome. 

As a research training opportunity, this award will give Joshua the opportunity to develop and expand his research skills and understanding. This will help, ensure he is well placed to pursue a career as a clinical academic - bringing his medical and research training together.