Health Story

03 December 2008 02:31 BST

Gene associated with major cause of blindness found

Scientists have discovered the first gene associated with a major cause of blindness.

A study by the University of California published in the New England Journal of Medicine outlines two important discoveries related to age-related macular degeneration (AMD), the leading cause of blindness in adults over 60.

As well as establishing the first gene associated with severe, "dry" macular degeneration, also known as geographic atrophy, researchers showed that there could be adverse consequences, including blindness, if individuals who possess a particular variation of the gene were treated with an experimental treatment currently being used on another form of AMD.

It was discovered that a link existed between dry AMD a key molecule that alerts the immune system to the presence of viral infection, a molecular protein called toll-like receptor three (TLR3).

A genetic variant associated with low activity of the TLR3 receptor appears to provide protection against dry AMD, perhaps by suppressing the death of certain retinal cells.

Today's report indicates that individuals with a genetic variant of TLR3 who undergo a new treatment called RNA interference (RNAi) could be at risk.

And the report's authors warn that those testing RNAi therapies for wet AMD need to be cautious and aware of a possible unintended side effect.

"If you are genetically susceptible to macular degeneration and are exposed to a virus that activates TLR3, it could lead to the death of cells in the macula," said Dr Kang Zhang from the University of California.

"Ironically, in some individuals, using RNAi to cure wet AMD might actually increase the risk for blindness from dry AMD."

Jayakrishna Ambati, from the University of Kentucky, added: "These findings pave the way for using TLR3 inhibitors as a potential new therapy for dry AMD, and simultaneously highlight the importance of critically assessing the potential risk posed to patients by RNAi-based therapies."

The use of RNAi can have the inadvertent effect of suppressing TLR3's protective role because it induces TLR3 activation. This then causes other cells to increase their anti-viral defences.

"What TLR3 does in the case of perceived infection is to sacrifice infected cells – in this case, retinal pigment epithilial cells – to protect the neighbourhood," said Nicholas Katsanis, from the Johns Hopkins School of Medicine.

"Biologically well-intentioned though the sacrifice may be, it can lead to blindness."