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How a Tiny Enzyme May Initiate Damage to the Eye in Diabetes

 

Research by Doheny Researchers Published in Diabetes in November 2025

A team of Doheny Eye Institute researchers, Mahesh Agarwal, PhD; Sathishkumar Chandrakumar, PhD; Irene Santiago Tierno, MS; Emma M. Lessieur, MD, PhD; and Kaustabh Ghosh, PhD, recently published important new findings in Diabetes that help explain how diabetic eye disease begins.

Doheny Eye Institute media

Their research focuses on lysyl oxidase, or LOX, a small enzyme the body uses to strengthen tissues. In diabetes, however, the body makes too much of it. This team had previously shown that this excess LOX stiffens the tiny blood vessels in the retina, causing vessel degeneration and loss of visual function. In the current study, they show that abundance of LOX can also “supercharge” neutrophils, a type of white blood cell. Instead of acting normally, these neutrophils become overly aggressive, thanks to LOX’s effect on actin, a protein that cells use to regulate their shape and movement. When these overactive neutrophils reach the retina, they injure the delicate cells that line the eye’s tiny blood vessels, setting the stage for diabetic retinopathy, a complication of diabetes that can lead to vision loss or blindness. Current treatments are limited to later disease stages and cannot reverse damage that has already occurred.

Why This Research Matters

Doheny Eye Institute media

Click on the above image to enlarge.

Understanding this chain reaction – excess LOX, overactive immune cells, and damage to retinal blood vessels – gives scientists a clearer picture of how diabetic eye disease starts long before symptoms appear. This opens the door to future possibilities for early treatment of the diabetic patient. Therapies that reduce LOX activity could help protect the retina by simultaneously calming neutrophils and normalizing retinal vessel stiffness. Development of new diagnostic tools that can measure LOX-related changes in the blood or eye could further improve clinical care by identifying individuals at higher risk of diabetic retinopathy.

In short, this discovery adds an important piece to the puzzle of diabetic retinopathy and points toward new ways to protect vision for millions of people living with diabetes.

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