Is the absence of the protein megalin responsible for high myopia?

  • Grant holder: Dr Tina Storm, Research Fellow
  • Institution: UCL Institute of Ophthalmology
  • Grant award: £9,769
  • Start date: August 2020
  • End date: February 2022

Why is this research needed?

Myopia, or short-sightedness, is estimated to become a leading cause of permanent blindness worldwide by 2050. For many people, myopia poses a much more serious problem than the inconvenience of having to wear glasses or contact lenses. People who are short-sighted, especially those who are severely so, are at significantly higher risk of developing sight-threatening conditions such as retinal detachment and macular degeneration in later life and could lead to permanent sight loss. The prevalence of myopia is on the rise and it is estimated that by 2050, some 5 billion people – half the world’s population – will be short-sighted, compared to around 1.4 billion today.

High myopia is better known as severe near-sightedness and is used to describe a condition where the eye has become longer (front to back) causing the light to focus in front of the retina instead of directly on it. This results in blurry vision and needs high prescription glasses to correct it. Severe near-sightedness increases the risk of other blinding conditions such as glaucoma, age-related macular degeneration, and detachment of retina.

Very little is known about what causes high myopia on a molecular level. Patients that do not have a particular protein called megalin, go on to develop a very severe form of high myopia suggesting that this protein is crucial for normal eye development.

What is megalin?

Megalin is a multifunctional protein in our bodies that is important for the healthy functioning of our organs, including our eyes, kidneys, and brain. In the eyes, it is found in the retinal pigment epithelium (RPE) layer of the retina where it helps RPE cells take up molecules from outside themselves that are required for multiple important cellular processes. Megalin is also potentially able to modulate communication between cells, which is vital for normal eye function as well as normal eye development in the foetus.

Detailed analyses of tissue from organs that lack megalin have revealed that the entire cellular machinery, responsible for uptake of molecules from outside the cell, is severely affected and not functional. This machinery is furthermore involved in formation and discharge of specialised transport vesicles, called exosomes, that carry important communication molecules to other cells. Recently, megalin was found on these exosomes suggesting that it may be important for their formation and release.

What is the aim of the project?

In this study, the researchers aim to determine whether the megalin protein is indeed essential for the formation and discharge of exosomes in the RPE cells, and if this could be the reason why patients without megalin become severely near-sighted.

How will this research help to beat sight loss faster?

This project will greatly improve our understanding of what causes severe near- sightedness and have the potential to identify new ways to treat or stop it. It may also lead to other important future projects that can help determine what roles exosomes play in diseases affecting other organs where megalin is also present such as in the kidneys and the brain.

Further information

Professor Jeremy Guggenheim at the University of Cardiff led another research project, funded by Sight Research UK, that explored the interaction between genetic and environmental risk factors for myopia. You can read about what he discovered here. We are also supporting other research in myopia and high myopia and you can read more here.

Not everyone who is severely short-sighted will develop other eye conditions, and for most people, their eyes will be healthy. The best way for everyone to look after their eyes is to have regular eye tests. An optician can spot early signs of eye conditions before you experience any symptoms, many of which can be treated if detected early enough. You can read about what’s involved in having an eye test here.

You can find more about the causes and symptoms of myopia and pathological myopia here.

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