Nine new research projects funded in our spring 2015 grants round

08 June 15

written by:

Ade Deane-Pratt

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The projects will take place at top UK institutions in Belfast, London, St Andrews, Edinburgh, Cardiff and Durham.

Fight for Sight has awarded over £1.4 million in new grants for world-class eye research. Nine 3-year projects will take place at top institutions around the UK, in Belfast, London, St Andrews, Edinburgh, Cardiff and Durham.

Researchers will investigate broad range of conditions from major causes of sight loss such as diabetic retinopathy and age-related macular degeneration (AMD) to rare inherited eye conditions and sight loss following childhood brain surgery.

Our Grants Assessment Panel meets 3 times each year to consider applications that have been peer reviewed by experts in the relevant field of ophthalmology and vision science. This time we received 26 high-quality applications but were only able to award 7 Project Grants and 2 Early Career Investigator Awards.

Commitment and dedication to eye research

“I am continually inspired by the high quality of the research applications we are asked to support and by the commitment and dedication of these internationally renowned researchers to tackling sight loss and eye disease,” said Dr Dolores M Conroy, Director of Research at Fight for Sight.

“In terms of scientific excellence, Fight for Sight research is second to none, but even as the largest charity funder of eye research in the UK, we have to turn down so many promising projects for lack of sufficient funds.

“However, I’m delighted that the range of work we have been able to support in this spring grants round is both firmly in line with Fight for Sight’s strategic goals and with research questions that are a priority for people affected by sight loss. We have made it our policy to bring the priorities identified by the Sight Loss and Vision Priority Setting Partnership to all of our grant applicants and they are doing an excellent job of taking those priorities on board.”

You can read a summary of our spring 2015 funded research projects below. 

 

Early Career Investigator Awards

 

Dr Alice Davidson, UCL Institute of Ophthalmology

The genetics of conditions that affect the cornea’s endothelial cell layer

The corneal endothelial dystrophies (CEDs) are conditions with various symptoms and different genetic causes. They all affect a thin layer of specialised cells (known as the endothelium) that line the back of the cornea (the transparent front surface of the eye). They can all lead to serious sight loss.

In this project, Dr Davidson will analyse DNA samples from a large group of CED patients at Moorfields. The aims are to identify both known and new genetic causes of CED and to investigate the overlap of relevant genes between common and rare types of CED. Finally, she will try to find out exactly how particular genetic faults cause corneal endothelial cells to fail, using cells from patients.

 

Dr Joe Rainger, University of Edinburgh

The genes and molecules involved in ‘keyhole’ eye development

Ocular coloboma is the most common eye condition affecting European children and accounts for up to 10% of blindness. People with ocular coloboma usually have a missing part at the base of their eye that means the iris is shaped like a keyhole instead of being round. The gap can happen if the eye doesn’t fully close during development. If the gap extends into the eye it can severely affect vision.

We don’t yet know much about the genetic causes of ocular coloboma. So in this study Dr Raigner will look at the genes and molecules involved when the eye develops normally and the gap fully closes. He will try to find out what can go wrong and whether it can be fixed.

Results from the project should also make it possible to relate people’s DNA data to the signs and symptoms they have. People with ocular coloboma may be able to have an accurate genetic diagnosis, and there may also be new potential targets for treatment.

 

Project grants

 

Prof Shin-ichi Ohnuma, UCL Institute of Ophthalmology

Generating eye tissue and whole eyes for research and treatment 

The eye is a very complex organ made up of several different types of tissue and types of nerve cells. They all have to be connected in the right way, but at the moment there is no good method for generating a whole eye system in the lab. 

However, the research team has recently discovered a protein that can cause eye tissue to develop in frog embryos. The tissue could be used for transplants to treat people with sight loss or to test new drugs.

So the team wants to find out how the protein works and then to improve the process, so they can produce eye tissue or even whole eyes from human stem cells. As well as improving treatment, the results could also mean we need fewer animal experiments in medical research on sight loss in the future.

 

Prof James Morgan, Cardiff University

What happens to optic nerve cells connections in glaucoma?

In glaucoma, the nerve cells that connect the eye to the brain (together called the optic nerve) become damaged. Previous animal studies have shown that damage to these connections happens in different stages, over a long period of time.

So now the team wants to find out if damage to human nerve cells follows the same pattern. They will use high-powered 3D-imaging to look at nerve cells in donated eyes from people with and without glaucoma. They will also try to see how the stage of nerve damage relates to data from the donor’s previous sight tests.

Results from the project will give us more information about nerve cells in glaucoma including whether there’s a window of time in which damaged optic nerve cells could be revived. If so, it may one day be possible to give sight back to people with sight loss from glaucoma. At the moment, this is impossible.

 

Prof Roy Quinlan, University of Durham

How does lens cell shape affect the way lenses work?

Cataracts form when proteins in the lens of the eye build up, turning the lens from clear to cloudy. But we don’t yet fully understand how the lens normally stays clear.

Cells that make up the lens have an internal ‘scaffolding’ that holds their shape. They also have cell membranes (the ‘skin’ that contains the cell) studded with channels that let water get in and out of the cell.

Both scaffolding and channels are important for the lens to change its focus point (so that we can focus on objects at different distances). And the research team may have discovered a link between the two and some types of inherited cataract.

So in this project, the researchers will try to find out more about how they interact. The results will provide the basic information needed to understand the lens better and for future cataract treatment research to build on.

 

Dr Alan Stewart, University of St Andrews

How do calcium and protein build up in the eye and what’s the link to AMD?

A hallmark feature of age-related macular degeneration (AMD) is that deposits of protein and fat (called drusen) build up underneath the light-sensitive part of the eye. Light-induced damage to cells in the retina means that they need to be repaired constantly. But as we age, the eye becomes less able to clear away the debris.

Recently, the team discovered tiny bits of a type of calcium (called HAP, usually found in teeth and bones) at the centre of deposits in eye tissue donated from people with AMD. The deposits also contained proteins previously linked to AMD, so in this project the team aims find out more about how these deposits form.

Results from the project could suggest new targets for treatment to prevent deposits forming, perhaps leading to preventing AMD altogether.

 

Dr Mei Chen, Queen’s University Belfast

Can gene therapy stop the inflammation that leads to diabetic retinopathy?

Diabetic retinopathy is a common complication of diabetes. It happens when the body’s immune system becomes over-active in response to damage from high blood sugar. The immune response (inflammation) can trigger unhealthy blood vessel growth in the retina – the light-sensing part of the eye – and this can lead to significant sight loss.

The researchers think that a key part of developing diabetic retinopathy could be having too little of a substance in the body that usually controls inflammation. They have already found that it’s reduced by high blood sugar, so in this project they want to find out if targeting the substance can prevent, delay or halt diabetic retinopathy.

 

Prof Michel Michaelides, UCL Institute of Ophthalmology

Planning a gene therapy clinical trial for a severe type of retinitis pigmentosa

X-linked retinitis pigmentosa (XLRP) is a severe inherited condition that leads to legal blindness by age 40. Symptoms start with night blindness, usually before the age of 10 and progress to losing peripheral (side) vision and finally central, detailed vision.

XLRP is due to a fault on the X chromosome, usually in a gene named RPGR. At the moment there is no cure, but researchers are planning to do clinical trials of gene therapy in the next 3-5 years. The idea is to engineer a safe virus to carry a healthy version of the gene into cells, replacing the faulty gene.

So in this study the team will collect the information they need to plan the clinical trial well. They will follow 60 people with XLRP due to a faulty RPGR gene for 3 years. The aim is to find out about how the exact genetic fault each individual has affects how their XLRP develops. For example, do some faults mean the condition progresses faster? The results will also help patients to have better genetic counselling about how the condition might affect them and their family.

 

Prof Christopher Clark, UCL Institute of Child Health

Improving children’s vision following brain surgery for epilepsy

Surgery is an important option for children with epilepsy that doesn’t respond to drug treatments. But, unfortunately, brain operations can damage the nerve cells and pathways involved in vision.

Studies in adults have shown that advanced magnetic resonance imaging (MRI) can be used to map the visual brain, but there haven’t been any studies in children yet. This is important because adult brains are different to children’s, including differences in the nature of epilepsy and visual problems after surgery.

So in this study the researchers will develop a process for using brain imaging to map the visual pathway in children. They also hope to relate how removing brain tissue affects the child’s vision.

This is the first study of its kind in children.

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