The little fish that's fighting blindness

A small tropical fish is proving very important in a study looking at how the effects of diabetes can damage the retina and eventually cause blindness, writes CLAIRE O'CONNELL

A FISH EYE is providing fresh insights into diabetic eye disease, and discoveries being made could widen the scope of future therapies.

The new zebrafish model of diabetic retinopathy – a complication of diabetes that can lead to blindness – indicates that light-sensitive cells at the back of the eye die off early in the disease, and protecting those cells may ultimately offer a way to help slow sight loss, according to Dr Brendan Kennedy, a senior lecturer at University College Dublin.

“The aim of the study was to try and understand diabetic retinopathy better,” says Kennedy, whose group at the Conway Institute carried out the research.

The condition, which is responsible for blindness in an estimated 2.5 million people worldwide, develops in two stages – an early phase where blood vessels at the back of the eye become leaky, and a later stage where the blood vessels grow inappropriately.

This late-stage growth of blood vessels is a target of therapies to help address the condition in humans, explains Kennedy. And while it might be more effective to intervene earlier in the condition, less is understood about how the disease develops in that initial stage.

In particular the fate of light-detecting cells at the back of the eye in the first phase is not clear. However, Kennedy’s group discovered that light-detecting cells at the back of the eye die off early in the zebrafish model of the disease, and they suggest that protecting these neurons could potentially offer another target for therapy.

To generate the model, the group allowed the fish to swim in a glucose solution every second day for 30 days, and this resulted in the fish developing an early stage of diabetic retinopathy, he explains.

They examined the fish for changes – even down to measuring their eyesight. “You can do an electroretinogram, the same thing you do in a human patient. You record the ability to respond to light,” explains Kennedy. “And these fish didn’t have normal electrical responses.”

One of the more unusual findings was that light-sensitive cells called “cones” in the retina were dying off in the model.

"This is something we wouldn't expect, that these photoreceptor neurons would be specifically affected," says Kennedy of the results, published in the journal Disease Models & Mechanisms. "It looks like it's an early hallmark of diabetic retinopathy."

The finding suggests that cone cell function should be further examined in human diabetic retinopathy, he adds.

“We don’t know what goes on in humans yet because most of the tissue is post-mortem, but there is some evidence in humans that they lose visual function before they have proliferative [late-stage] disease.”

Ultimately if cone cells in the eye are also dying off early in the condition in humans, then shoring up those cells may be able to help, Kennedy believes.

“The real issue is to see if these cones are affected in humans, and if they are affected at an early stage then you get a different therapeutic target,” he says.

“The current treatments really only target the blood vessels, but this study indicates that it should be considered more closely whether cone photoreceptors are affected in diabetic retinopathy as well as looking at the blood vessels.

“So, our argument would be that if you can try and protect these neurons from dying at an early stage maybe you can delay the later stage disease. It gives you an alternative therapeutic target.”

The group, which receives funding from Science Foundation Ireland and the Health Research Board, is now looking to develop a zebrafish model that can shed light on the later stage of diabetic retinopathy and which could also relate to other degenerative eye diseases.