A recent study identifies new ways in which high sugar levels destroy vision, leading to diabetic eye disease. These findings are the basis for the future development of a new treatment for diabetic retinopathy.
Diabetic retinopathy is an eye disease causing blindness. Diabetic retinopathy accompanies high blood glucose levels, often appears without any preceding symptoms, and usually requires surgical intervention. According to Dr. Sayon Roy from the Department of Medicine and Ophthalmology of the Boston University School of Medicine: “Diabetic retinopathy is the leading cause of blindness in the working-age population,” and there is no real cure for this difficult eye problem. How exactly elevated glucose levels kill retinal cells in the eye is not exactly understood. It is known, however, that some metabolites lead to cell death in other conditions. One such metabolite is Lysyl oxidase propeptide (LOX-PP). LOX-PP is a known toxin to different tissues, causing cell death in various diseases.
In a recent study published in the American Journal of Pathology, American researchers studied whether LOX-PP is related to glucose-mediated eye cell death. First, the researchers examined whether LOX-PP affected blood vessels in the retina in healthy and diabetic rats. They administered a synthetic LOX-PP directly into healthy or diabetic rat eyes and monitored for pathologies characteristic of diabetic retinopathy, such as swelling and changes to healthy blood vessel functioning. The study found that diabetic rats had more retinal vascular disorders in comparison to healthy rats. Moreover, healthy rats who received LOX-PP, developed vascular malfunctions in their eyes, which are characteristic of pathologies associated with diabetic retinopathy. Next, the researchers studied how high glucose levels affect the growth and development of eye cells. They found that glucose causes elevation of LOX-PP levels, which in turn promotes eye cell death.
In a recent press release, Dr. Roy further explains: “We found that hyperglycemic and diabetic conditions increased LOX-PP levels. LOX-PP may induce cell death by compromising a cell survival pathway, and in retinas of diabetic rats, increased LOX-PP contributed to retinal vascular cell death associated with Diabetic retinopathy. The administration of LOX-PP alone was enough to induce cell death. This report shows novel functionality of LOX-PP in mediating cell death under high glucose conditions in retinal endothelial cells as well as in diabetic animals.”
The implications of this study are huge. It is the first time that a direct link has been established between high glucose levels and a toxic metabolite in a model of eye disorder. Further experiments are clearly needed as well. In these future efforts, scientists have to answer the question regarding the exact role of LOX-PP in diabetes-associated vascular abnormalities in the eye. Once more light is shed on that mystery, drug development possess can hopefully kick in.
Written by Marina Chemerovski-Glikman, PhD
Kim, D., Lee, D., Trackman, P. C., Roy, S. Effects of High Glucose–Induced Lysyl Oxidase Propeptide on Retinal Endothelial Cell Survival Implications for Diabetic Retinopathy. Phatol, 2019.