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Diabetic mice to let scientists study vision loss

A new mouse model that exhibits symptoms of diabetic retinopathy, a disease that often causes blindness, could lead to future translational research, say researchers.

Diabetic retinopathy affects adults who have had diabetes mellitus for 10 years or more. Estimates are that 600 million people will have some sort of the disease by 2040.

Until now, no good animal models existed that scientists could use to study the disease, its diagnosis, or potential treatments.

“Diabetic retinopathy is a common retinal complication of diabetes mellitus that can be categorized in different stages in humans,” says Shyam Chaurasia, assistant professor of ophthalmology and vision sciences research at the University of Missouri.

“Multiple interlinked pathways—including malfunctions in the immune system—lead to cellular damage. These vascular and neuronal abnormalities in the retina lead to ‘blind spots’ and complete blindness. With the prevalence of diabetes reaching record levels, it is important to develop the tools needed to combat this disease.”

As reported in Scientific Reports, researchers focused on a specific inflammasome, a protein responsible for the activation of inflammatory responses, called the NLRP3 inflammasome.

Long-term hyperglycemia results in the activation of the NLRP3 inflammasome causing vascular leakages in the retina and eventually leading to neovascularization—the formation of new blood vessels or networks in the retina.

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Using advanced retinal imaging techniques, scientists tested the diabetic mice that processed NLRP3. Using a new technique called laser speckle flowgraphy, they were able to create a “heat map” of blood flow volume and found significantly decreased levels in the NLRP3 mice.

The mice also showed an increased prevalence of a buildup of macrophages in the retina that could be caused by immune responses involved in chronic inflammation that leads to diabetic retinopathy.

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“Several new techniques and potential diagnostics are demonstrated in this study for the first time, including the laser speckle flowgraphy technique, which may prove useful in the diagnosis of human DR,” Chaurasia says.

“This is the first study to show that the activation of the NLRP3 inflammasome is involved in the proliferative changes observed during DR progression, proving that this mouse model could be useful in screening potential drugs to fight the disease.”

Source: University of Missouri

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