Brief plain language background
Dominant optic atrophy (DOA) is the most common genetic disease that affects the optic nerve, causing progressive and irreversible blindness with a prevalence of 1:25,000 in the UK.
DOA has a gradual onset in early childhood and typically presents with bilateral, symmetrical, central visual loss and affects the ability to distinguish between colours (dyschromatopsia), caused by the loss of retinal ganglion cells (RGCs). Visual loss is progressive, and the majority of patients are registered legally blind by the fifth decade of life. 60 to 70% of cases of DOA are caused by disease associated variants in the OPA1 gene.
What problem/knowledge gap does it help address
The OPA1 gene is involved with mitochondria – the tiny ‘powerhouses’ of our cells. Poorly functioning mitochondria can lead to damage and cell death in the optic nerve and RGCs, and ultimately, significant vision loss.
Mitochondrial optic nerve diseases, such as DOA, have proved challenging to treat. Small molecules and drugs have shown potential to protect RGCs but do not modify the progression of the condition. Gene therapy treatments aim to remedy this, but these are time consuming and costly to develop and administer.
Aim of the project
To test an existing dietary supplement and medication, nicotinamide, as a novel therapy for dominant optic atrophy.
This project also aims to further the career progression of the applicant, who hopes to establish a research group studying the link between nerve degeneration, changes in the retina, mitochondrial integrity and vision.
Key procedures/objectives
Analyse the RGCs in treated and untreated mice with and without the faulty OPA1 gene.
Potential impact on people with sight loss
If successful, utilising a readily available medication to not only preserve but recover RGCs could be of clinical benefit to those with mitochondrial optic neuropathies.