An international team representing 18 research groups has identified seven new loci (regions of the human genome) that are associated with advanced age-related macular degeneration (AMD). In all, they identified 19 loci.
The team undertook a meta-analysis of genome-wide association studies to look for genetic variations associated with AMD. Over 17,000 people with advanced AMD and over 60,000 people with normal vision (controls) were studied. The results are published online on Monday (March 4) in Nature Genetics .
AMD is one of the leading causes of blindness in people over 60 years. In the case of India, 10 to 20 per cent of people over 60 are said to be suffering from advanced AMD. As longevity increases, the number of those suffering from this kind of blindness is increasing in the country, and is becoming comparable to the developed countries.
In India, the “19 loci identified account for about 30 per cent of the variability in disease risk” (owing to the high prevalence of the condition).
Rods and cones, essential for vision, are concentrated in the central region of the retina called macula. AMD affects this. Reading, writing, face recognition, to name a few, are affected by macular degeneration. Age is the biggest risk factor, but smoking, diet, alcohol consumption, diabetes, and genetic risk factors are also significant risk factors.
The seven new loci identification will go a long way in providing therapies. “We have found an association of the loci with AMD. This will help us in future studies for developing therapies that are directed at particular set of genes so the vision is retained for a longer period of time,” said Dr. Parveen Sen from Sankara Nethralaya, Chennai. She is a senior consultant in the retina services and was part of the research group that did the study.
Providing genetic treatment is still far away. “But we have identified the loci which code for specific proteins. And these proteins may be responsible in some ways for maintaining vision. Even though we are not able to replace or repair the faulty genes, we can always supplement or replace the protein which is not being produced,” she said.
In other words, it is based on the fact that the biochemical factors that get altered as a result of the faulty genes can always be supplemented.
Immediate medical attention is essential in the case of wet advanced AMD (the other being the dry advanced AMD) caused by leaky new blood vessels formed under the retina. This can cause rapid deterioration of vision in about 6-12 months.
In the last decade, biochemical markers have been indentified for wet advanced AMD. For instance, vascular endothelial growth factors (a protein) are higher in this kind of AMD. Molecules that can combat the excessive biochemical activity of this factor have been developed. And this has become possible only by the identification of the 12 loci. “They have improved our understanding of the disease, helped us in developing molecules that can be given as injection/drops to treat patients with wet advanced AMD,” Dr. Sen stressed.
But not all patients respond to treatment. In some cases, injection has to be given once every month. With the cost of one injection being prohibitively high (Rs. 40,000 to 50,000), only a few stand to gain.
“The identification of novel genes and pathways involved in the disease enables the pursuit of a larger range of disease-specific targets for the developments of new therapeutic interventions,” the paper notes.
