How does good cholesterol affect AMD?
An MDFA Research Grant is allowing Dr Carla Abbott to investigate the links between lipids and macular disease, potentially paving the way for new treatments.
You’ve probably seen the term ‘good cholesterol’ in the media, but you might not have heard its proper name: high density lipoprotein, or HDL.
HDL is called good cholesterol because it helps to remove bad cholesterol from the body, which protects against heart disease, stroke and cell death.
However, high levels of HDL have been reported in several studies to be associated with a higher risk of age-related macular degeneration (AMD).
That’s why Macular Disease Foundation Australia has awarded Dr Carla Abbott an MDFA Research Grant to explore the role of lipids in the development of AMD.
There is currently no treatment to prevent people with early-stage AMD from progressing to late-stage AMD and losing their central vision.
Dr Abbott’s research will investigate pathways involved in progression, by improving our understanding of how and why AMD develops — focusing specifically on the role of HDL.
Our team has preliminary evidence showing that AMD patients have a higher level of dysfunctional HDL in the blood. So ultimately, we think it’s not just the total amount of HDL in the bloodstream that’s important, but also the composition and functionality.Dr Abbott
“That could explain why we see there’s a protective element for high levels of HDL in cardiovascular disease — but if it’s dysfunctional, then it could be linked with a higher risk of AMD.”
The MDFA-funded project will recruit patients into the Macular Research Units clinic at the Centre for Eye Research Australia (CERA) to take images of their retinas, as well as a blood sample.
The retinal imaging determines the patients’ stage of AMD (early or late), as well as whether they have reticular pseudodrusen (RPD) — a subtype associated with a higher risk of progressing to the late stage of AMD, and may ultimately require different treatments.
Meanwhile, the blood samples are investigated in the laboratory, where amongst other tests, the HDL is extracted, and then undergoes a series of assays to test whether the HDL is working properly or not.
Dr Abbott will then compare how HDL functions in people with different stages of AMD and the higher risk phenotype to better understand how HDL dysfunction is connected to the progression of the disease.
Dr Abbott underlines that this collaboration between clinical and laboratory work is a team effort, involving Prof Robyn Guymer, the head of CERA’s Macular Research Unit, and Dr Manisha Shah, who expertly runs the time-consuming and technical assays.
“If we find all these differences that show it’s dysfunctional HDL that’s the problem, rather than just the total amount of HDL in the blood, then we can look at ways to target improving the functionality of the HDL.
“A potential intervention to restore HDL function can then be tested in a clinical trial in the future as a potential treatment to prevent people with early-stage AMD progressing to the vision-threatening late stage of AMD.
“Previous work in our unit, and that of others, has suggested statins, which impact cholesterol levels, might be beneficial for AMD disease progression and there are strong genetic signals that also point to lipids being involved in AMD.
Taken together with this current work, there seems increasing evidence to implicate lipids in the cause of AMD. It’s hoped the results from this study will pave the way for new therapies, impacting lipids, which might be possible for AMD.Dr Abbott
While it’s a long road before any pharmaceuticals hit the shelves, this research is an important stepping stone.
If we can show that this dysfunctional HDL has a role in AMD development, then we can look at the next steps of trying to develop a drug that can improve HDL functionality.Dr Abbott
Dr Abbott has been interested in eye health ever since she received her first pair of glasses as a child.
After studying Optometry, Dr Abbott wanted to delve deeper into eye disease — especially conditions without an effective treatment, such as atrophic AMD — through her PhD.
An expert in retinal structure and function, Dr Abbott began working in macular disease five years ago at CERA under the guidance of Prof Guymer, co-investigator on this project and an inaugural MDFA Research Grant recipient.
Dr Abbott still works in public health optometry on a Saturday, so she witnesses the impact of macular disease on our community.
“It’s one of the leading causes of blindness in over-50s, and vision has such a big effect on people’s quality of life. So if we can make a difference in macular disease, it’s going to have a big impact on so many people.
“My main motivating factor is to save sight, give people better quality of life, and try to actually make a difference for diseases like this where it has such a big impact on people’s lives, but there just hasn’t been treatment at the early stages of disease.”
Dr Abbott also understands how difficult it is to find funding for research into eye disease.
National Health and Medical Research Council (NHMRC) grant applications have a very low success rate, and the total bucket of money researchers are vying for remains limited.
However, the MDFA Research Grants Program — made possible by the wonderful support of our generous donors — has enabled this vital project, which could snowball into a groundbreaking treatment for AMD.
“We’re extremely grateful to MDFA and the donors for their support of this work,” Dr Abbott says.
“It makes a big difference in being able to get these studies up and running, which enables us to potentially apply for larger pools of funding as well.
“The next steps for this are potentially running a trial in patients but without this initial support, we just can’t proceed.”
Published: 30 October, 2023