Investigating the genetics of macular degeneration
Dr Amanda Carr | GR001324
19 May 2021
New work from Dr Amanda Carr at the UCL Institute of Ophthalmology hopes to reveal how genes impact on the development of macular degeneration. Her team will use patient-derived cell lines and genetic sequencing technology to tackle this important question.
Macular diseases are a leading cause of vision loss in the UK. These diseases affect a layer of cells at the back of the eye called the retinal pigment epithelium (RPE). Loss of these cells means the retina can’t function properly and central vision is compromised. There are several types of macular disease, including age-related macular degeneration (AMD) and bestrophinopathies.
What is age-related macular degeneration (AMD)?
Over 600,000 people in the UK are affected by AMD. This disease is predominantly found in people over 50 years old and comes in two forms:
1. Dry AMD
- This is caused by a build-up of waste material under the macula
- Dry AMD makes up around 75% of cases
- People with dry AMD will normally not have severe sight loss
- Around 1 in 4 people with dry AMD go on to develop the more serious form - wet AMD
2. Wet AMD
- This is when abnormal blood vessels start to grow underneath the retina and leak blood and fluid
- Eventually, wet AMD can result in the permanent loss of central vision, but peripheral vision will remain
What are bestrophinopathies?
Bestrophinopathies are inherited forms of macular degeneration that primarily affect RPE cells. These diseases are caused by mutations in a protein called BEST1, and can affect a patients’ vision from a young age.
Similar to AMD, bestrophinopathies are caused by the build-up of waste material and fluid under the macular layer.
Dr Amanda Carr and her team are trying to find out how vision loss develops by studying the early stages of macular disease in patient-derived RPE stem cells lines.
However, the team can’t currently see the full picture because they don’t know the genetics of the patient RPE stem cells they are working with.
Genes are known to play a role in the development of macular disease so having the full genetic background of patient cells is important. Sequencing their RPE cells would give the team the opportunity to study how genes impact the development of AMD and bestrophinopathies and they could even use this knowledge to potentially develop personalised medicines.
Finding a solution
Over the next three years Dr Carr’s team will genetically sequence RPE cells from patients with AMD or bestrophinopathies.
They will use this information to identify genetic variants that are found in AMD patients but not in people without AMD. The team will then assess the effects of genetics on the early stages of AMD. The team will also sequence the affected gene in patients with bestrophinopathies.
They hope that this genetic information can be used to develop new genome editing therapies, such as CRISPR/Cas9, for patients with inherited forms of macular disease.
Knowing the genetic background of patients will help to illuminate how macular disease starts and progresses. This genetic information will also lay the foundations to be able to develop and test new therapies for macular disease.
Research project grant
Dr Amanda Carr
Age related macular degeneration, genetics/inherited eye disorders, retinal/vitreo-retinal