Establishing biomarkers as a predictor of age-related macular degeneration

  • Grant holder: Professor Glen Jeffery, Professor of Neuroscience, and Dr Pardis Kaynezhad, Postdoctoral Researcher
  • Institution: UCL Institute of Ophthalmology
  • Grant award: £93,230
  • Start date: February 2020
  • End date: February 2022

Why is this research needed?

Age related macular degeneration (AMD) is currently 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. A poor understanding of exactly what causes the macula to become damaged means that AMD is currently incurable. While treatments exist for the wet form of the disease, there is still no treatment for the most common form: dry AMD.

In addressing the challenges presented by this condition, Professor Jeffery’s approach is to focus on preventing its onset rather than treating its symptoms.

What is the goal of the project?

This project asks whether it is possible to assess the retina’s function in healthy individuals in a way that could predict whether someone is likely to develop AMD in later life. Early detection of susceptibility provides options for lifestyle changes that could have a significant protective impact to stave off the onset of AMD, or even avoid it altogether.

Professor Jeffery and Dr Kaynezhad will assess the health of the retina by testing its mitochondrial function. They will do so by shining a dim light onto the retina and recording the strength of the signal that is returned back in real time showing how healthy the mitochondria are. This interdisciplinary approach is made possible by combining Professor Jeffery’s interest in mitochondria with Dr Kynezhad’s back ground in Biomedical Engineering.

If the mitochondrial signal returned is clear, researchers will also aim to establish whether there is a difference between the strength of the signal in younger and older individuals. They will also assess whether there are biomarkers that can clearly show, even at an early age, that an individual is particularly vulnerable to the onset of AMD.

Why are mitochondria important in AMD?

You can think of mitochondria as a cell's power station that produces the energy for it to carry out all its functions properly. They work in a similar way to a digestive system: they take in nutrients and generate energy by breaking them down. This process is called cellular respiration and mitochondria use oxygen to release energy to the cell. 

With ageing, or disease, however, mitochondria have been shown to perform their digestive function less well, which, in the eye, can lead to inflammation in the retina. Inflammation is known to be correlated with AMD, therefore declining mitochondrial function in the retina is an important marker of potential susceptibility to AMD. 

What are biomarkers? 

Biomarkers (short for biological markers), provide a very useful way to look for biological signs of the presence of a disease, and even to assess how a patient is reacting to treatment for that disease. The presence or absence of a particular biomarker, or even their level, can help a doctor diagnose a patient with a disease. 

Researchers and clinicians look for biomarkers either in images (such as those obtained through scans), or in molecules that can be associated with a particular disease. These molecules can be anything from DNA, antibodies, or proteins, and even smaller molecules.

What will the project do?

Researchers will shine a safe infrared light in the eyes of human volunteers and will use imaging devices to record reflections from their retinas. Confirming that is it possible to record these signals in humans is critical to any form of clinical progression identifying those individuals who may be at greater risk of AMD. Professor Jeffery and his research team will liaise with Professor Sobha Sivaprasad at Moorfields Eye Hospital to design the testing equipment in a way that is suitable to progress to the next stage of clinical research.

How will this research help prevent sight loss?

Early results have been encouraging so far, and this research can take significant steps towards establishing a biomarker for mitochondrial diseases of the retina. This would have implications not only for AMD but also diabetic retinopathy and Leber’s Hereditary Optic Neuropathy where mitochondrial failure occurs. The hope is to uncover biomarker information before disease is established. 

The ultimate goal of the project is that, if successful, it would pave the way to large scale screening that could become routine in high street optometry practices. Such large scale screening would offer a very important additional diagnostic opportunity to help prevent AMD developing in the first place. This would be through counselling the patient on a series of lifestyle interventions (diet, exercise, smoking cessation, etc.) and potentially other lifestyle aspects such as choosing certain types of medication over others not to tax their immune system.  

Further information

You can find more about the causes and symptoms of AMD here

Around 700,000 people in the UK have late-stage AMD, and nearly 200 people are diagnosed every day. 

Your gift can help find new sight-saving solutions for the UK’s biggest cause of sight loss. 

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