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MicroRNAs Block Abnormal Blood Vessel Growth While Still Maintaining the Health of Normal Vessels

The research team from The Scripps Research Institute (TSRI) in California, Mount Sinai Hospital in Canada and the University of California, San Diego (UCSD), say their findings could lead to new treatments to prevent blindness.

 

Many types of blindness, including diabetic retinopathy and macular degeneration, can be linked to the abnormal growth of blood vessels (neovascularization) in the retina at the back of the eye, the researchers explain. The retina is a thin layer of soft tissue consisting of blood vessels and light-sensing cells.

 

According to the Center for Disease Control and Prevention (CDC), around 1.6 million Americans over the age of 50 suffer from macular degeneration, while 5.3 million people worldwide aged 18 or over have diabetic retinopathy, emphasizing the need for treatments for these diseases.

 

In order to determine how the abnormal growth of blood vessels in the retina can be stopped, many studies over the last decade have focused on a molecule in the human body called vascular endothelial growth factor (VEGF).

 

The researchers explain that when the body senses too little oxygen, it triggers VEGF. Once the vessels in the eye sense high levels of VEGF, this causes them to produce more “shoots.”

 

Furthermore, VEGF and other molecules that prompt the growth of blood vessels, activate a gene called Ras that has to be triggered before new blood vessels can grow. Using this information, researchers believed that if VEGF can be stopped, this could potentially provide a cure for blindness.

 

However, research from the team at TSRI last year found that VEGF plays an important part in maintaining healthy vision. If VEGF were to be blocked, this could kill light-sensing cells in the eye, causing severe loss of vision.

 

This discovery meant researchers were now on the hunt for new ways to prevent abnormal blood vessel growth, and David Cheresh and colleagues at the Department of Pathology at UCSD found that microRNAs may be the answer.

 

Testing the theory on mice, the UCSD laboratory discovered that microRNAs – small pieces of RNA known to adjust gene activation and expression – could be used to target neovascularization in the VEGF pathway at a “downstream” point, preventing Ras activation.

 

This means that microRNAs are able to block the formation of abnormal blood vessel growth and still maintain the health of normal blood vessels in the eye.

 

Commenting on the findings, Prof. Martin Friedlander of the Department of Cell and Molecular Biology at TSRI said, “We believe that targeting and inhibiting the action of microRNAs involved could represent a novel and effective way to treat a broad range of neovascular eye diseases such as diabetic retinopathy, macular degeneration and macular telangiectasia.¬†We are excited about this approach to halting abnormal blood vessel growth without inducing off-target side effects.”

 

Prof. Friedlander says it is hoped this approach will reach clinical trials. He notes that one pharmaceutical partner has already shown interest in teaming up with the research team once the therapy is advanced for human use.

 

However, he emphasizes that clinical trials could take many years, as the treatment needs to be proved safe and effective prior to routine availability.

 

“Are we ready to go to the clinic tomorrow? No,” adds Friedlander. “But is this class of therapeutics “druggable?” The answer is yes.”

 

Source: Medical News Today, October 27, 2013