Resource to tackle age-related macular degeneration
Prof John Marshall, Dr Amanda Carr, Dr Emily Eden | GR001164
1 May 2021
Researchers at the UCL Institute of Ophthalmology are establishing a resource to supply patient-derived age-related macular degeneration cell lines. These will be used to accelerate research and understanding of this common cause of sight loss and aid potential future therapeutic avenues.
Age-related Macular Degeneration (AMD) is the most common cause of vision loss in older people, yet remarkably there are no effective treatments to stop or prevent vision loss.
In AMD, progressive degeneration of retinal pigment epithelium (RPE) - the cells that make up the macular at the back of the eye - can result in vision loss. However, very little is known about the early stages of AMD - what events trigger the degeneration and eventual loss of these cells.
people have AMD by age 60
people in the UK are affected by AMD
Research is needed from a variety of different angles to tackle these big questions but much has been hampered by a lack of disease models.
Underpinning a lot of this type of research therefore is the need for a new human model system to investigate eye disease.
Finding a solution
With support from the charity, the UCL Institute of Ophthalmology will establish a preclinical platform to supply AMD patient-derived RPE cells.
These cells will be used for a range of applications aimed at advancing our understanding of AMD, identifying targets for early therapeutic intervention and testing potential therapeutic strategies.
The cause of AMD is not known, which is what makes it so challenging to study in the lab. However, there are a number of factors, such as age and genetics, which determine someone’s risk of developing AMD. A number of projects investigating these factors are underway at the institute and will greatly benefit from the valuable resource provided by this stem cell hub.
1. Creating aged models of AMD disease
Professor Pete Coffey and Dr Amanda Carr will use this unique resource to characterise how AMD patient-derived cells age and degenerate under controlled laboratory conditions. Specifically, they will examine whether some genetic changes can influence the proteins in the cell as it ages and, importantly, how this affects the cell’s health and behaviour.
2. Clearing the toxic debris
The retinal pigment epithelium (RPE), which is affected in many degenerative eye conditions including AMD, plays a role in the healthy function of the light sensing cells – photoreceptors. 10% of these lipid-rich photoreceptors are shed daily. The shed cells are normally engulfed and processed by neighbouring RPE cells.
However, when this doesn’t happen, as in AMD, it leads to an accumulation of lipid-rich and toxic material which stops the RPE from working properly. Dr Emily Eden and her team will aim to identify mechanisms involved in lipid clearance and potential ways to reverse lipid accumulation.
3. Optimisation of the retinal rejuvenation therapy
Another avenue of research which will utilise cells from the hub is led by Professor John Marshall. His team will look at optimising a retinal rejuvenation therapy (2RT) laser system for intervention in AMD. This work will involve RPE grown on specialised culture chambers and monitoring of proteins released from the cells.
The creation of a centralised stem cell hub of RPE cells at the UCL Institute of Ophthalmology will be an invaluable resource for many researchers working on AMD, and will empower other researchers to move into the field.
RPE cell culture models of AMD generated by the research programmes will be used for diverse areas of research, including:
- examining the molecular pathology of AMD,
- testing novel methods for lipid clearance, and
- identifying potential therapeutic targets.
These and future studies will allow us to further understand the complexities of AMD, which will be key to developing viable therapies that could serve to delay or prevent AMD-related vision loss. Findings from these studies could also be applied to other retinal dystrophies, thereby offering exciting new opportunities to tackle vision loss.
Research project grant
Professor John Marshall, Dr Amanda Carr, Dr Emily Eden
Macular degeneration, age related macular degeneration