Targeting autophagy to treat age-related macular degeneration
- Grant holder: Dr Jian Liu
- Institution: University of Bristol
- Grant award: £69,587
- Start date: September 2021
- End date: Oct 2024
Why is this research needed?
Age-related macular degeneration (AMD) is the leading cause of severe and permanent sight loss in the UK, and in the developed world. This progressive disease damages the macular: the part of the eye that is responsible for our central, detailed, and much of our colour vision. AMD is currently incurable and, for the most part, untreatable. While treatments exist for the wet form of the disease, there is still no treatment for the most common form: dry AMD.
What is making the problem even more pressing is that people are now living much longer than 50 or even 30 years ago making the prevalence of this condition among the over 60s much higher. The suffering and cost of vision loss are dramatically increasing.
As we age, AMD typically begins with the appearance of deposits in the eye, but there are currently no treatments available to clear the abnormal deposits, if normal biological processes perform less well with age. This study seeks to find ways to stimulate autophagy (the body's natural waste disposal process) to clear the deposits that build up in the eye and prevent damage to the retina.
What is autophagy and why does it matter?
Autophagy (which literally means “self-eating”) is the normal waste disposal process of recycling and reusing wastes and by-products of biological processes.
A biological tug-of-war occurs during ageing: on the one hand, accumulation of metabolic waste occurs in the eye and, on the other, autophagy slows down. The result is an excess build-up of waste, which damages the retina.
What is the aim of the project?
Ageing is irreversible and accumulation of waste build up cannot yet be prevented, but improving the waste clearance through effective autophagy could slow down and even prevent vision loss as we age.
This study aims to test the effectiveness and safety of selected compounds in stopping the progression of disease at an early stage which could preserve sight and for longer.
These compounds have been chosen because they provide several advantages: they are small enough to enter the cells; their autophagy activating capacity has already been proven to be of benefit in other age-related illness; they can be administered by mouth; are suitable for long-term use; and are relatively cheap.
One of these compounds (trehalose) has already been proven to see reduced oxidative damage and maintained energy (mitochondrial function) in laboratory models of macular degeneration.
This study will test more drug candidates, firstly in cellular models of AMD, and then in more complex models of the disease. In doing so, researchers will assess whether the selected compounds are safe and effective in activating autophagy, and if so, at what dose. Secondly, the group will seek to understand what makes the tested compounds effective by looking at which genes and molecules are involved in the process of autophagy reactivation. Finally, researchers will focus on what next steps would need to be taken to translate these scientific findings into new therapies for patients with AMD.
How will this research help to beat sight loss faster?
If successful, this project will deliver a treatment to stop AMD progression and result in great benefits for patients with improved health and quality of life.
You can find more about the causes and symptoms of AMD here.
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