Clinical round-up

Hannah Flynn takes a look at research surrounding diabetic retinopathy and wet AMD.

Genes causing blindness identified

Genes controlling inherited blindness have been discovered by a team from the University of Leeds School of Medicine, with the results of the study published in the journals Nature Genetics and the American Journal of Human Genetics.  

The genes found can cause conditions such as Leber’s congenital amaurosis, an eye condition that appears at birth or in the first few months of life, cone-rod dystrophy and eye development defects.

Researchers sequenced the genes of people who had been blind since birth as a result of these conditions, to work out which genes were controlling the expression of the conditions.

The team looked at over 100 Pakistani families in West Yorkshire and in Pakistan. They also looked at over 2000 individual patients to identify the genes that cause the conditions. Pakistani families were looked at due to an increased rate of marriage to relatives in that community, and an increased rate of these conditions within the community.

“When we know that there is consanguinity in the people it means that there will be a particular pattern of inheritance," said Professor Chris Inglehearn, who worked on the research.

He added that a mapping process would be used to work out which genes were causing the mutations.

Once the genes have been identified then people can be screened for them from any community or ethnic background, he adds.

One benefit of identifying these genes is that people can now be screened to find out if they have them, and provided with more accurate information regarding their condition, the likelihood that it will progress and also which treatments can be used and how successful they may be.

The team is now planning on piloting a diagnostic screen, so that individuals with known mutations can be put forward for clinical trials.

Controlling the progression of AMD

Controlling the presence of a protein in the eye, could be used to prevent the development of wet age-related macular degeneration (AMD), a study published in the international medical journal, Nature Medicine has shown.

A key feature of dry AMD is the formation of a product called drusen in the eye. A significant number of cases of the “dry” form of AMD can progress to the “wet” form, where blood vessels underneath the retina begin to grow, leading to central blindness.

Researchers found that the accumulation of drusen in the macula can lead to the production of two proteins calledIL-1beta and IL-18.

“The progression from “dry” to “wet” AMD appears to be mediated by IL-18, our results directly suggest that controlling or indeed augmenting the levels of IL-18 in the retinas of patients with dry AMD could prevent the development of the wet form of disease,” says Dr Sarah Doyle, Assistant Professor in Immunology at Trinity College Dublin. This is as it suppresses the production of damaging blood vessels behind the retina.

The findings were based on studies involving drusen isolated from four donor eyes as well as studies carried out on groups of up to ten mice.

“We shone a laser into the retina of the mice to induce the growth of blood vessels in the retina, to simulate AMD. This model is good at showing what drugs will work, and Lucentis and Eylea were proven in this model first,” co-author Doyle explains.

“We were able to show that injecting IL-18 into the eye works better than current therapies. IL-18 stops VEGF being produced in the eye,” she explains.

VEGF causes the formation of blood vessels in the eye and is the target of anti-VEGF treatments.

The use of IL-18 is known to be safe in humans as it has been used in cancer treatment intravenously in the past, with a low rate of side effects.

Detecting early warning signs of diabetic retinopathy

Indiana University researchers have detected new early-warning signs of the potential loss of sight from diabetic retinopathy, and reported the results in the journal, Biomedical Optics Express.

They have shown that damage to the retina happens much earlier in some diabetic retinopathy patients than previously thought, following a study of seven diabetics. 

In order to visualise the early warning signs, the team developed an instrument that uses adaptive optics to obtain a sharp image, and minimised optical errors.

This means small capillaries in the eye appear quite large on a computer screen in a video format, which allows observation of blood cells moving through the blood vessels.

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