Robo4 Gene – ‘Major Breakthrough” for Eye Diseases

By Anna Boyd
13:52, March 18th 2008
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Robo4 Gene – ‘Major Breakthrough” for Eye Diseases

New research reveals that a gene called Robo4 could help curb or prevent two leading causes of blindness: age-related macular degeneration (AMD) and diabetic retinopathy.

AMD is a medical condition that affects mostly the elderly and in which the center of the lining of the eye, known as the macula area of the retina suffers thinning, atrophy, and in some cases, bleeding. This can result in loss of central vision, which entails inability to see fine details, to read, or to recognize faces.

According to the American Academy of Ophthalmology, AMD is the leading cause of central vision loss (blindness) in the U.S. today for those over the age of fifty years, effecting more than 10 million individuals.

Diabetic retinopathy caused by complications of diabetes mellitus can also lead to blindness. The disease affects up to 80 percent of all diabetics who have had diabetes for 10 years or more.

The University of Utah study suggests a new therapeutic target for these two ophthalmic diseases, as well as other conditions marked by inflammation and vascular leakiness, including cancer and certain traumatic injuries.

“Many diseases are caused by injury or inflammation destabilizing blood vessels and causing them to leak fluid into adjacent tissues as well. We found a natural pathway – the Robo4 pathway – that counterattacks this by stabilizing blood vessels. Robo4 tells the vessels not to grow, to stabilize, not to explore. The blood vessels have an instruction system that tells them to do the opposite, to stabilize,” study senior author Dr. Dean Li of the University of Utah School of Medicine in Salt Lake City said, according to the Telegraph.co.uk.

Dr. Li, along with Dr. Kang Zhang, also of the University of Utah, mutated the Robo4 gene in mice. Activating the Robo4 gene shored up leaky blood vessels and curbed the development of new blood vessels, Dr. Zhang found in a series of experiments in test tubes and mice.

To do that, the Robo4 gene countered a chemical called vascular endothelial growth factor (VEGF), which signals the creation of new blood vessels. This way, Robo4 prevented VEGF from issuing the “let’s make some blood vessels” order.

The Robo4 gene not only stopped the uncontrolled growth of the weak and leaky eye vessels, it also reversed the vessel damage. Dr. Li said clinical trials on human would probably take place within the next 5 year.

Dr. Randall Olson, director of the John A. Moran Eye Center at the University of Utah, welcomed the University of Utah study, calling Dr. Li’s findings historic.

“This is a major breakthrough in an area where the advances have been minimal. We are excited about taking this opening and moving the frontier forward with real hope for patients who have but few, often disappointing, options,” Dr. Olson said.

The study was published in the March 16 online edition of Nature Medicine.

 



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