Explained: How a small protein can cause blindness in diabetics

Researchers have shown how a small protein that can both damage or grow blood vessels in the eye can cause vision loss in people with diabetes, an advance that may lead to better treatment of the disease.

By combining data on optometry patients' eyes with advanced computational methods, researchers from Indiana University in the US created a virtual tissue model of diabetes in the eye.

The findings show precisely how a small protein that can both damage or grow blood vessels in the eye causes vision loss and blindness in people with diabetes, researchers said. The study could lead to better treatment for diabetic retinopathy, which currently requires multiple invasive procedures that are not always effective in the long term.

Diabetic retinopathy is responsible for 1% of all blindness worldwide, researchers said. "With the current epidemic of diabetes in adults, the number of people with vision damage from diabetes will continue to rise," said Thomas Gast from Indiana University. "Therapeutically, understanding a disease can lead to improved treatments," he added.

Dr. Thomas Gast of the IU School of Optometry, center, with John Gens, left, and Xiao Fu of the IU Biocomplexity Institute.
Image Credit: Indiana University 

A major way diabetic retinopathy threatens vision is diabetic edema. In this condition, the smallest vessels supplying the retina with oxygen become leaky, causing fluid to swell the central retinal area and impairing the type of vision required for precise activities such as reading.

This happens because the loss of blood flow in a blood vessel causes the local oxygen level to drop, which stimulates local production of vascular endothelial growth factor (VEGF), a protein that in most tissues causes the growth of new blood vessels to repair damage, researchers said.

However, in a retina with elevated sugar levels, instead of repairing the damage, physicians observe a cascade of damage that propagates from the initial blocked vessel. The rate and area of the damage's progression also vary greatly between patients in a seemingly unpredictable way.

The virtual retina model in the study provides the first strong evidence for why this pattern of disease progression is so variable, and it predicts where damage will occur next. It shows that the blockage of one vessel causes a local loss of oxygen in the retina, which triggers release of VEGF that spreads over a larger region which, in turn, increases the probability of blockage in the surrounding vessels, creating a "domino effect," researchers said.

The spread of damage from region to region depends on the detailed pattern of blood vessels in each patient and the amount of blood they carry, both of which vary greatly from person to person, they said.

Based on a patient's specific vascular structure, the scientists' new model calculates how much a blockage in one blood vessel will increase the probability of blockage in each neighbouring vessel.
As a result, their programme predicts the specific rate and pattern of cascading vascular damage in the individual.

The findings were published in the journal PLOS Computational Biology.