Nav: Home

Poor anti-VEGF responses linked to genetic variation in immune regulation

December 05, 2016

Anti-VEGF therapies are commonly used to stabilize deteriorating vision in patients with wet age-related macular degeneration (wet AMD). Vascular endothelial growth factor, or VEGF, is a signaling molecule that helps maintain blood vessels in the eye and other organs, but its overabundance in wet AMD patients can lead to overgrowth of vessels that causes vision loss. Though reducing VEGF signaling with anti-VEGF therapies has positive effects in many patients, some individuals continue to experience vision deterioration during treatment. In a study published this week in the JCI, Martin Friedlander's lab at Scripps Research Institute investigated whether genetic variation in an immune system component called the complement system may contribute to vision loss during anti-VEGF therapy in some wet-AMD patients. Prior work suggested that patients who do not respond well to anti-VEGF therapy often expressed variations in the genes encoding complement system proteins, but it was not known whether these variations interacted with VEGF signaling during treatment. In the current study, researchers examined the these genetic variations in human retinal cells and observed that they led to complement system dysregulation. Blocking VEGF signaling enhanced this dysregulation, providing evidence for a link between VEGF signaling and complement system activation. These findings suggest that screening wet AMD patients for genetic variations in the complement system may help identify individuals at risk for adverse responses to anti-VEGF therapy.
-end-
TITLE: VEGF regulates local inhibitory complement proteins in the eye and kidney

AUTHOR CONTACT: Martin Friedlander
Scripps Research Institute
friedlan@scripps.edu

View this article at:http://www.jci.org/articles/view/86418?key=0485356af1f7871ce520

JCI Journals

Related Genetic Variation Articles:

Poor anti-VEGF responses linked to genetic variation in immune regulation
Though reducing VEGF signaling with anti-VEGF therapies has positive effects in many patients with wet age-related macular degeneration, some individuals continue to experience vision deterioration during treatment.
Out of sync: How genetic variation can disrupt the heart's rhythm
New research from the University of Chicago shows how deficits in a specific pathway of genes can lead to the development of atrial fibrillation, a common irregular heartbeat, which poses a significant health risk.
New insights into human genetic variation revealed: Nature paper
A powerful new analysis of the protein-coding region of the human genome known as the exome will boost efforts to pinpoint clinically relevant genetic variations linked to human disease.
Defining the consequences of genetic variation on a proteome-wide scale
Combining two emerging large-scale technologies for the first time -- multiplexed mass spectrometry and a mouse population with a high level of natural genetic diversity --researchers at Harvard Medical School (HMS) and The Jackson Laboratory (JAX) can crack an outstanding question in biology and medicine: how genetic variants affect protein levels.
RNA splicing mutations play major role in genetic variation and disease
RNA splicing is a major underlying factor that links mutations to complex traits and diseases, according to an exhaustive analysis of gene expression in whole genome and cell line data.
Genetic variation shown in patients with severe vascular complications of infection
Major infections such as influenza and bacterial sepsis kill millions of people each year, often resulting from dangerous complications that impair the body's blood vessels.
Genetic variation may explain Asian susceptibility to Kawasaki disease
Scientists from the RIKEN Center for Integrative Medical Sciences (IMS) in Yokohama, Japan, in collaboration with researchers from a number of hospitals around Japan, have found two variations in a gene called ORAI1, one of which may help explain why people of Asian descent are more susceptible to Kawasaki disease, a poorly understand ailment that mostly afflicts young children.
Enormous genetic variation may shield tumors from treatment
The most rigorous genetic sequencing ever carried out on a single tumor reveals far greater genetic diversity among cancer cells than anticipated, more than 100 million distinct mutations within the coding regions of its genes.
Genetic variation is key to fighting viruses
Using a genome-wide association study, EPFL scientists have identified subtle genetic changes that can cause substantial differences to how we fight viral infections.
Poor survival in multiple myeloma patients linked to genetic variation
Researchers have found that multiple myeloma patients with a genetic variation in the gene FOPNL die on average 1-3 years sooner than patients without it.

Related Genetic Variation Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...