Dominant optic atrophy (DOA) is an important cause of inherited blindness in children, affecting at least 1 in 25,000 people in the UK.[1] DOA is caused by gradual degeneration of the optic nerve, which carries visual signals from the eyes to the brain, causing progressive and irreversible sight loss from early childhood. Professor Mike Cheetham at the UCL Institute of Ophthalmology is using advanced stem cell and gene-editing technologies to identify key genes involved in optic nerve cell death. He hopes to uncover new treatment approaches that could help slow or stop sight loss in children with DOA, improving their quality of life.
How are children’s lives affected now?
DOA is caused by the progressive loss of specialised nerve cells in the light-sensitive tissue at the back of the eye. The death of these cells leads to the degeneration of the optic nerve, disrupting the transmission of visual information from the eyes to the brain.
“A child with DOA will typically begin to lose central vision – which is crucial for recognising shapes, colours and fine details – before their 10th birthday,” says Professor Cheetham. “While the severity of the disease varies, sight loss usually worsens over time, and many individuals will eventually be registered as legally blind.”
Around two out of three children with DOA have faults in the OPA1 gene2, which contains the instructions to make a protein crucial for the healthy function of mitochondria* – the cell’s energy-generating powerhouses. Cells with defective mitochondria can die prematurely, especially those with high energy demands, such as nerve cells.
“Unfortunately, there are currently no treatments that can help prevent or reverse sight loss in children with DOA,” says Professor Cheetham.
*Mitochondria are tiny structures inside cells that produce energy. They are often called the ‘powerhouse’ of the cell.
How could this research help?
Our goal is to identify genes that could be targeted with drugs to slow or prevent optic nerve cell death in DOA.
The researchers have leveraged advanced stem cell technologies to create an ‘optic nerve in a dish’ using cells from DOA patients, providing a powerful new laboratory model for studying the disease.
“We will now apply a cutting-edge gene-editing technology to switch off each of the thousands of genes in the human genome in our model – and assess its impact on cell survival,” says Professor Cheetham.
The team hopes to pinpoint key genes involved in the death of optic nerve cells – and then determine whether targeting these genes could help extend cell survival.
“Ultimately, we hope to identify promising new targets for drugs that could help slow down or prevent the loss of optic nerve cells, helping to preserve and prolong vision in children and young adults with DOA,” says Professor Cheetham.
Research table
Project details
| Project Leader | Professor Mike Cheetham PhD |
| Location | UCL Institute of Ophthalmology |
| Project Team |
Dr Michael Whitehead PhD
Professor Patrick Yu-Wai-Man MBBS PhD FRCOphth FRCPath |
| Other Locations | Department of Clinical Neurosciences, University of Cambridge |
| Grant Awarded | |
| Grant Amount | £199,995 |
| Start Date | TBC |
| End Date | TBC |
| Duration | 27 months |
| Grant Code (GN number) | GN3052 |
References
- Yu-Wai-Man P & Chinnery PF. Dominant optic atrophy: novel OPA1 mutations and revised prevalence estimates. Ophthalmology. 2013;120(8):1712-1712.e1
- Wong DCS, et al. OPA1 Dominant optic atrophy: Pathogenesis and Therapeutic Targets. J Neuroophtalmol. 2023;43(4):464-474.
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