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New Study Identifies Potential Enzyme Target for Diabetic Retinopathy

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A new study shows that diabetic retinopathy (DR), or retinal disease caused by the high blood glucose levels in diabetes mellitus, is due to the death of retinal cells because of the high levels of a pro-enzyme called lysyl oxidase propeptide (LOX-PP). This could help researchers develop specific treatments by targeting this molecule.

The study was reported online in The American Journal of Pathology on September 16, 2019.

Diabetic retinopathy causes serious loss of vision in about one third of diabetics, and is the No. 1 cause of blindness in people of working age. Its characteristics include early lesions like the development of capillaries lacking cells, and the loss of pericytes. Cell loss is associated with the thickening of the vascular basement membrane in the retinal blood vessels, a characteristic microscopic feature of DR.

An enzyme called lysyl oxidase (LOX) is a contributor to cell loss. Prior research indicates that its pro-enzyme form LOX-PP is also involved in triggering the process of programmed cell death, or apoptosis, in unhealthy tissue. Several studies have suggested its contribution to apoptosis by suppressing the AKT pathway by inhibiting the addition of an activating phosphorus group. This is a pathway necessary for cell survival.

The LOX enzyme is involved in strengthening collagen and elastin networks by crosslinking them to provide structural stability in the extracellular matrix, which supports all tissues. However, the role of LOX-PP is not clear, though it has been suggested that it keeps LOX inactive, requires the addition of glucose for the optimal activation of the LOX enzyme, and suppresses several cellular pathways.

This motivated the current study on the effects of LOX-PP (mediated by high blood glucose or diabetes) on the retinal blood vessels.

High glucose and diabetes increases LOX-PP levels and cell death

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Schedule4 Oct 2023