Blind World Magazine

Infection plays key role in age-related blindness disease.




Telegraph.
March 6, 2006.




A new genetic discovery suggests that infection and inflammation play a role in the majority of cases of age-related macular degeneration (AMD), a leading cause of blindness in the elderly.


The genes, Factor H and Factor B explained nearly three out of four AMD cases. The study shows that 74 per cent of patients carry variants in one or both genes that increase the risk of this disease.


Published in Nature Genetics by a team led by Prof Rando Allikmets at Columbia University Medical Centre, New York, it follows the discovery that several variants in the Factor H gene significantly increase the risk of developing AMD.


Factor H encodes a protein that helps shut down an immune response against bacterial or viral infection, once the infection is eliminated. People with these inherited risk-increasing variations of Factor H are less able to control inflammation caused by infectious triggers, which may spark AMD later in life.


The investigators decided to look for additional culprits and focused on genes in the same immune response pathway that contains Factor H. Their genetic analysis of 1,300 people quickly identified Factor B as the major modifier of the disease.


The discovery makes biological sense: while Factor H is an inhibitor of the immune response to infection, Factor B is an activator. Because of the complementary roles of the two genes, a protective Factor B variation can protect against AMD, even if one carries a risk-increasing variant of Factor H, and vice versa.


Prof Allikmets said: "These findings confirm the roles of these two genes and, consequently, the central role of a specific immune response pathway, in the development of AMD. We now have clear targets for early therapeutic intervention."


More than 50 million people worldwide are estimated to have irreversible blindness as a result of macular degeneration, making it the most common cause of blindness for those over 60. It is estimated that 30 per cent of the population will have some form of AMD by the time they reach the age of 75.




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