Dominant optic atrophy (DOA) is the most common inherited disease of the optic nerve and a cause of progressive blindness in children and young adults. Patients with DOA can experience irreversible loss of a specific type of nerve cell in the eye, the retinal ganglion cell.

The challenge

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.

The person

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.

Against a background of reducing national investment in academic ophthalmology, we thank the charity for supporting research training fellowships. They enable promising young clinicians to launch their research careers and take the results of research into the clinic.”

Professor Miles Stanford, chair of the charity’s scientific advisory panel.

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.

The potential

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.

Project Details

Funding scheme

Research training fellowship

Grant holder

Dr Joshua Harvey

Award level

£286,299

Start date

October 2020

Grant reference

GR001138