Neurodegenerative proteinopathy in Glaucoma
Research type
Research Study
Full title
A histological and immunohistochemical analysis of motor neurone disease-related proteinopathy in glaucoma
IRAS ID
209097
Contact name
John Highley
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
The retina has evolved from part of the brain and forms the lining at the back of the eye that captures images from the eye and starts to process them. Glaucoma is a degeneration of the retina due to raised fluid pressures in the eye. There is growing recognition that this degeneration may involve similar molecular mechanisms to those seen in age-related degeneration of the brain (neurodegeneration), including pathological accumulations of protein (proteinopathy), neurone loss and scarring (gliosis). The existing literature shows that microscopic analysis of the retina in glaucoma reveals similar protineopathies to that seen in Alzheimer disease (one form of neurodegeneration).
Interestingly, mutations of some of the genes (Ataxin 2, Optineurin and C9ORF72) that can cause motor neurone disease (MND, another form of neurodegeneration) can also cause glaucoma. Optineurin protein can form pathological protein aggregates in brain cells in motor neurone disease. A single case report of a case of C9ORF72-related MND shows classical MND style proteinopathy in the retina. This raises the possibility that some of the pathology seen in MND may occur in glaucoma.
We wish to study this issue in wafer-thin slices of surplus tissue from eyes surgically removed to treat the pain of medically untreatable glaucoma and to compare these eyes with those removed to treat other conditions, such as tumours next to but outside the eyeball.
We will use antibodies to detect these MND-related proteins (a method called immunohistochemistry) as well as to examine neuronal loss and glial scarring where relevant.
This will help us to improve our understanding of both glaucoma and MND specifically and neurodegeneration more generally. This will inform efforts to monitor and develop treatments for both conditions.
REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
16/NW/0614
Date of REC Opinion
10 Aug 2016
REC opinion
Favourable Opinion