Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

NIH Study Suggests Immune System Could Play a Central Role in AMD

Published: Thursday, November 29, 2012
Last Updated: Thursday, November 29, 2012
Bookmark and Share
First epigenetic study reveals the molecular mechanisms for any eye disease.

Changes in how genes in the immune system function may result in age-related macular degeneration (AMD), the leading cause of visual impairment in older adults, based on preliminary research conducted by National Institutes of Health (NIH) investigators.

"Our findings are epigenetic in nature, meaning that the underlying DNA is normal but gene expression has been modified, likely by environmental factors, in an adverse way," said Dr. Robert Nussenblatt, chief of the National Eye Institute (NEI) Laboratory of Immunology. Environmental factors associated with AMD include smoking, diet, and aging.

Dr. Nussenblatt continued, "This is the first epigenetic study revealing the molecular mechanisms for any eye disease."

The study identified decreased levels of DNA methylation, a chemical reaction that switches off genes, on the interleukin-17 receptor C gene (IL17RC).

The lack of DNA methylation led to increased gene activity and, in turn, increased levels of IL17RC proteins in patients with AMD. IL17RC is a protein that promotes immune responses to infections, such as fungal attacks.

The study, conducted by research teams from the NEI and other NIH institutes, including the National Heart, Lung, and Blood Institute and the National Center for Complementary and Alternative Medicine; the University of Melbourne, Australia; and Oregon Health and Science University, appears in the Nov. 29 issue of Cell Reports.

"Our study also suggests IL17- and IL17RC-mediated immune responses can be crucial in causing AMD," added Dr. Lai Wei, also of NEI's Laboratory of Immunology and first author on the paper. "By measuring IL17RC gene activity in at-risk patients, we have also potentially identified an early method to detect AMD."

AMD damages the light-sensitive cells of the macula, the central part of the retina that allows us to see fine visual detail.

As the disease progresses, patients encounter great difficulty reading, driving, or performing hobbies and tasks that require hand-eye coordination.

Treatments exist to prevent severe vision loss in certain types of advanced AMD but none prevent or cure the disease. Currently, 2 million Americans have advanced AMD and another 7 million have intermediate stages.

Recent studies have identified several genes with alterations that increase the risk of developing the disease. In addition, environmental risk factors have also been suggested as possible causes of the disease.

One explanation may be that environmental exposures influence DNA methylation, which regulates gene expression. Changes in this process may result in the production of too much or too little of a gene’s protein, leading to cellular dysfunction and disease.

Changes in DNA methylation have been implicated in cancer, lupus, multiple sclerosis, and many other diseases.

To test whether changes in DNA methylation might play a role in AMD, the investigators evaluated three pairs of twins - one pair identical and two pairs fraternal - where only one of the siblings had AMD.

Identical twins have the same genetic makeup while fraternal twins share about half of their DNA. Because of their similar genetic backgrounds, identical and fraternal twins can be helpful in studying the differences between the effects of genetics and the environment.

When compared with the unaffected twins, methylation patterns were altered in 231 genes of affected twins. This finding is consistent with the hypothesis that environmental exposures may epigenetically regulate expression of many genes and lead to AMD.

Among the 231 genes, the investigators found that DNA methylation was absent in a region of the IL17RC gene in twins with AMD.

The lack of methylation in the IL17RC gene led to increased gene activity and, in turn, increased levels of its protein in circulating blood.

The investigators further validated these findings by comparing seven siblings with and without AMD as well as 202 AMD patients and 96 control subjects without the disease. These studies also found increased IL17RC levels in circulating blood and, most importantly, in the retina of patients with AMD but not controls.

Based on these results, the authors propose that chronic increased levels of the IL17RC protein in the retina likely promote inflammation and recruitment of immune cells that damage the retina and lead to AMD.

“This study strongly implicates epigenetic DNA methylation as another crucial biological pathway for understanding the molecular basis of AMD,” according to Nussenblatt.

The investigators next plan to evaluate what environmental factors may be responsible for the regulation of IL17RC and how the epigenetic regulation leading to the chronic inflammation in AMD patients can be reversed by novel therapies. They will also evaluate the role of epigenetics in other eye diseases.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Tuesday, April 12, 2016
Decoding Ties Between Vascular Disease, Alzheimer’s
NIH consortium uses big data, team science to uncover complex interplay of factors.
Tuesday, March 15, 2016
Researchers Find Link Between Death of Tumor-Support Cells and Cancer Metastasis
Researchers at NIH have found that the lifespan of supportive cells in a tumor may control the spread of cancer.
Tuesday, February 23, 2016
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH-funded study could lead to new tick control methods.
Tuesday, February 09, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Thursday, February 04, 2016
Genome-Wide Study Yields Markers of Lithium Response
An international consortium of scientists has identified a stretch of chromosome that is associated with responsiveness to the mood-stabilizing medication lithium among patients with bipolar disorder.
Monday, February 01, 2016
Schizophrenia’s Strongest Known Genetic Risk Deconstructed
Suspect gene may trigger runaway synaptic pruning during adolescence – NIH-funded study.
Thursday, January 28, 2016
NIH Genome Sequencing Program Targets the Genomic Bases of Common, Rare Disease
The National Institutes of Health will fund a set of genome sequencing and analysis centers whose research will focus on understanding the genomic bases of common and rare human diseases.
Friday, January 15, 2016
Three Glaucoma-Related Genes Discovered
NIH-funded genetics analysis of glaucoma is largest to date.
Tuesday, January 12, 2016
International Study Reveals New Genetic Clues to AMD
NIH-funded research provides framework for future studies of AMD biology, therapy.
Tuesday, December 22, 2015
Dementia Linked to Deficient DNA Repair
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer’s disease.
Tuesday, December 01, 2015
Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Scientific News
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
A lncRNA Regulates Repair of DNA Breaks in Breast Cancer Cells
Findings give "new insight" into biology of tough-to-treat breast cancer.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
Computational Model Finds New Protein-Protein Interactions
Researchers at University of Pittsburgh have discovered 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia.
MicroRNA Pathway Could Lead to New Avenues for Leukemia Treatment
Cancer researchers at the University of Cincinnati have found a particular signaling route in microRNA (miR-22) that could lead to targets for acute myeloid leukemia, the most common type of fast-growing cancer of the blood and bone marrow.
Analysis of Dog Genome will Provide Insight into Human Disease
An important model in studying human disease, the non-coding RNA of the canine genome is an essential starting point for evolutionary and biomedical studies – according to a new study led by The Genome Analysis Centre (TGAC).
New Insights into Gene Regulation
Researchers have solved the three-dimensional structure of a gene repression complex that is known to play a role in cancer.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!