Diabetic retinopathy

BioMed Radio - Washington University School of Medicine in St. Louis

Diabetes-related vision loss most often is blamed on blood vessel damage in and around the retina, but new research indicates that much of that vision loss may result from nerve cell injury and probably begins long before any blood vessels are damaged. The findings � from scientists at Washington University School of Medicine in St. Louis � may lead to new approaches to treating diabetes-related vision loss, called diabetic retinopathy, since many current treatments are aimed at damaged blood vessels.

MANY PEOPLE WHO HAVE DIABETES ALSO EVENTUALLY SUFFER DIABETES-RELATED VISION LOSS FROM DIABETIC RETINOPATHY. IT�S ONE OF THE MOST COMMON CAUSES OF VISION LOSS IN WORKING-AGE PEOPLE AND OFTEN IS BLAMED ON BLOOD VESSEL DAMAGE IN AND AROUND THE RETINA, BUT NEW RESEARCH FROM WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS SUGGESTS THE LOSS OF VISION MAY BEGIN LONG BEFORE ANY BLOOD VESSELS ARE DAMAGED. JIM DRYDEN HAS THE STORY�

THE RESEARCHERS CREATED A MOUSE MODEL OF DIABETIC RETINOPATHY, THE FIRST SUCH MODEL TO CAUSE THE DISEASE THE SAME WAY IT DEVELOPS IN MOST PEOPLE: BY EATING A HIGH-FAT DIET. IN FACT, FIRST AUTHOR RITHWICK RAJAGOPAL SAYS THE ORIGINAL GOAL OF THE STUDY WAS MAINLY TO DEVELOP A BETTER ANIMAL MODEL. HE SAYS THE MOST COMMON ANIMAL MODELS OF THE DISORDER HAVE SOME PROBLEMS.

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The most common one uses a toxin to poison the beta cells,
to stop them from secreting insulin, and it works really well
to make the mice deficient in insulin. But the problem is that
the toxin also has collateral effects, and one of them is
neurotoxicity. So we didn�t think that was going to be very
good when we wanted to study a neurologic tissue like the retina.

RAJAGOPAL, AN OPHTHALMOLOGIST AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS, SAYS SOME 30 MILLION PEOPLE IN THE U.S. HAVE DIABETES, AND A LARGE PERCENTAGE ALSO DEVELOP RETINOPATHY. HE SAYS IN THE EXPERIMENTS WITH MICE, IT TOOK A LONG TIME BEFORE THE HIGH-FAT DIET CAUSED VISION PROBLEMS OR BLOOD VESSEL DAMAGE IN THE RETINA, BUT THAT TURNED OUT TO BE A GOOD THING.

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They developed disease so slowly that we could unmask very different
stages of disease. And so they, initially, went through this phase
where they developed functional problems � which we think are primarily
due to defects in the way the neurons and the glia are working in the
retina � and then, eventually, they developed vascular disease that
was typical of mouse, and human, retinopathy.
MOST THERAPIES FOR DIABETIC RETINOPATHY CONCENTRATE ON TREATING THAT VASCULAR DAMAGE, BUT AS THE MICE DEVELOPED THE CONDITION, RAJAGOPAL, AND HIS COLLEAGUE CLAY SEMENKOVICH, FOUND THAT DAMAGE TO NERVE CELLS IN THE EYE PRECEDED THE BLOOD VESSEL DAMAGE.

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There is evidence that people with diabetes go through a phase
that probably reflects early neuronal injury. But this has been
ignored because the dogma is that this is a blood vessel disease,
so nerves shouldn�t be involved.

BUT, IN THIS STUDY, THE NERVES WERE DAMAGED FIRST, WHICH, SEMENKOVICH SAYS, COULD MEAN THAT SOME THERAPIES FOR DIABETIC RETINOPATHY SHOULD TARGET NERVE DAMAGE, RATHER THAN BLOOD VESSEL DAMAGE, AND HE SAYS THOSE THERAPIES COULD BEGIN EARLIER IN THE COURSE OF THE DISORDER, WHEN THE NERVE DAMAGE BEGINS.

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And the truly profound implications of this study is the fact that
neuronal injury may occur early; people knew about this a long time
ago but have, kind of, forgotten it; and now we have an animal model
that will allow us to develop mechanistic-based therapies that can
decrease suffering.

AND RAJAGOPAL SAYS USING THIS MOUSE MODEL COULD POTENTIALLY PAY BIG DIVIDENDS FOR PEOPLE WITH DIABETIC RETINOPATHY, DUE TO THE FACT THAT THE DISEASE PROGRESSES IN THE MICE IN A VERY SIMILAR WAY TO HOW IT PROGRESSES IN PEOPLE.

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And so our mouse is actually the first diabetic retinopathy
model to recapitulate exactly what we think happens in humans.

RAJAGOPAL AND SEMENKOVICH PUBLISHED THEIR FINDINGS IN THE JOURNAL DIABETES. I�M JIM DRYDEN…

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