Researchers have identified how an excess of glucose in the blood leads to the production of an enzyme, itself linked to cell death at the origin of diabetic retinopathy. This discovery gives hope for a new therapeutic target in the prevention of diabetes-related blindness.
Diabetic retinopathy is an ocular complication affecting nearly half of type 2 diabetics. In France, 40% of diabetics, or 1 million patients, have diabetic retinopathy. Very serious, this pathology is linked to the occlusion of the retinal capillaries, which causes ischemia of the retina, the sensory membrane of the eye, and can lead to blindness in the absence of appropriate treatment.
In a new study published in The American Journal of Pathologyresearchers from the Boston University School of Medicine demonstrate that chronic hyperglycemia increases levels of an enzyme called lysyl oxidase propeptide (LOX-PP), which promotes cell death that causes blindness.
The role of LOX-PP in diabetic retinopathy
“We found that hyperglycemia and diabetes increased LOX-PP levels,” explains Sayon Roy, principal investigator of the work.
To reach this conclusion, his team studied the role of LOX-PP in the retinal tissue of rats. The scientists injected the synthesized enzyme directly into the eyes of rodents divided into two groups: a group of diabetic rats and a control group. Some animals in both groups also received a control injection.
They then found that the injection of LOX-PP contributed in both groups to the appearance of symptoms linked to diabetic retinopathy: swelling and leakage of blood vessels, obstruction or thickening of the vascular walls. , as well as the appearance of acellular capillaries and pericyte loss.
These symptoms were however more important in the retina of the diabetic rats than in that of the control rats having received the injection of LOX-PP.
The hope of a therapeutic treatment
The researchers also studied the effect of a high level of glucose on retinal endothelial cells, which are particularly affected in cases of diabetic retinopathy, and found during in vitro cultures that hyperglycemia contributed to cell death. Same observation with cells exposed to LOX-PP. According to them, these results indicate that a high level of glucose increases the level of LOX-PP, which, in turn, promotes cell death. Moreover, LOX-PP appears to induce cell death by compromising a pathway involved in cell survival.
“Diabetic retinopathy is the leading cause of blindness in the working-age population,” says Dr. Roy. “Unfortunately, there is no cure for this devastating ocular complication. Our results suggest a new mechanism of high-glucose-induced cell death involving the enzyme LOX-PP, which could be a therapeutic target in the prevention of retinal vascular cell loss associated with diabetic retinopathy.”
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