Gene linked to aggressive 'wet' age-related macular degenerationNovember 27, 2006A gene variant that increases the risk of developing the aggressive "wet" form of age-related macular degeneration (AMD), the most common cause of blindness in people over age 50, is reported in two recent articles in Science by researchers at Yale School of Medicine. AMD causes light-sensitive cells in the retina to break down, resulting in progressive loss of central vision. Of the two forms of AMD, the "dry" is more common than the "wet" form. Wet macular degeneration can rapidly lead to blindness, while the dry AMD progresses more slowly. Last year, Josephine Hoh, associate professor in the Departments of Epidemiology & Public Health and Ophthalmology at Yale and senior author on one of the two new studies, identified a gene for dry AMD and found that both wet and dry AMD are associated with a variant in the complement factor H (CFH) gene on chromosome 1.
Hoh now reports they have found a single nucleotide polymorphism (SNP)-a one-base change in the sequence-of the regulatory part of the HTRA1 gene on chromosome 10 that leads to greatly increased risk of developing the wet form of AMD. According to Hoh, buildup of abnormal blood vessels in Caucasian patients is compounded by development of large waste deposits called drusen. Chinese patients, she said, develop little to no drusen and progress directly to wet AMD. This study demonstrates that these two major genes, CFH and HTRA1, in two different biological pathways, each affect the risk for a distinct component of the AMD phenotype: CFH influences the drusen of dry AMD, whereas HTRA1 influences blood vessel development, the hallmark of the wet disease type. When the two processes are combined, it leads to the composite characteristics that are seen in some cases of AMD. Hoh, her collaborators in Hong Kong, and her colleagues at Yale including Michael Snyder and Colin Barnstable in the Departments of Molecular, Cellular and Developmental Biology and Molecular Biophysics and Biochemistry, and Ophthalmology, did trans-racial gene mapping by comparing genomes between precisely defined populations to find the incidence of SNP in a Chinese population-96 with AMD and 130 with normal vision. "We found that patients with the HTRA1 SNP were 10 times more likely to have wet AMD than those without this gene variant," said Hoh. "While this is only preliminary work, it points to possible directions for future treatment of wet AMD." Hoh also worked on a replication study led by Kang Zhang at the University of Utah School of Medicine that found a link between the same SNP and AMD. Zhang and his team studied 581 Caucasian patients with AMD and 309 with normal vision. These patients had wet AMD as well as a large amount of drusen. To confirm the association, the Utah team also examined several donor eyes and measured the expression of the gene and the encoded protein. They found that the expressions were elevated in the eyes of patients who carry HTRA1. "The marker we have identified is very much associated with AMD, but no one has ever pinpointed the clinical features of the gene. We need to conduct further analysis in order to understand the biological mechanisms," said Hoh. Yale University Science News and Science Current Events Tag Cloud This tag cloud is a visual representation of term frequencies of random science news topics with common terms grouped together and emphasized by their display size. Tumor cell Longevity Aging Nanoscale Gravitational Wave Stem cells Radiotherapy Ace Inhibitors Antimicrobial Influenza Schizophrenia Behavioral Problems Diabetes Bone Density Crohn's Disease Endangered Species Biodiesel Marine Species Ebola Polycystic kidney disease Melanoma Huntingtons Disease Birth Defects Brain function Progesterone
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Related Macular Degeneration Current Events and Macular Degeneration News Articles 'Nature' and 'nurture' variables early predictors of AMD Like many diseases, causes for age-related macular degeneration (AMD) can be categorized as either "nature" or "nurture". Structures from the human immune system's oldest branch shed light on a range of diseases How molecules of the oldest branch of the human immune system have interconnected has remained a mystery. Omega-3 fatty acids appear to impact AMD progression Omega-3 fatty acids found in fatty fish such as tuna and salmon may protect against progression of age-related macular degeneration (AMD), but the benefits appear to depend on the stage of disease and whether certain supplements are taken. Major Breakthrough in Early Detection and Prevention of AMD A team of researchers led by Dr. Jayakrishna Ambati at the University of Kentucky has discovered a biological marker for neovascular age-related macular degeneration (AMD), the leading cause of blindness in older adults. UNC study suggests new approach to common cause of blindness Researchers at the University of North Carolina at Chapel Hill School of Medicine in collaboration with lead investigators at the University of Kentucky have identified a new target for the diagnosis and treatment of age-related macular degeneration, the most common cause of blindness in older Americans. Why do people with Down syndrome have less cancer? Most cancers are rare in people with Down syndrome, whose overall cancer mortality is below 10 percent of that in the general population. Erectile dysfunction treatments do not appear to damage vision over 6 months Two medications used to treat erectile dysfunction in men (tadalafil and sildenafil) do not appear to have visual side effects when taken daily for six months, despite concerns about eye-related complications. Growth factor TGF-B helps maintain health of retinal blood vessels Scientists at Schepens Eye Research Institute have found that the growth factor known as TGF-β is essential to the health of blood vessels in the retina and that blocking it can cause retinal dysfunction. Ambati study published in PNAS The side effects of an experimental "gene-silencing" treatment that is currently being investigated for a variety of diseases are even more wide-ranging than previously discovered, according to a study by a University of Kentucky researcher. Mutated gene in zebrafish sheds light on blindness in humans Among zebrafish, the eyes have it. Inside them is a mosaic of light-sensitive cells whose structure and functions are nearly identical to those of humans. More Macular Degeneration Current Events and Macular Degeneration News Articles |
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