Navigation Links
NIH study suggests immune system could play a central role in AMD
Date:11/28/2012

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. "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 twinsone pair identical and two pairs fraternalwhere 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.


'/>"/>

Contact: NEI Communications Office
neinews@nei.nih.gov
301-496-5248
NIH/National Eye Institute
Source:Eurekalert

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. Law that regulates shark fishery is too liberal: UBC study
3. New study will help protect vulnerable birds from impacts of climate change
4. Study jointly led by UCSB researcher supports theory of extraterrestrial impact
5. BYU study: Using a gun in bear encounters doesnt make you safer
6. 15-year study: When it comes to creating wetlands, Mother Nature is in charge
7. Pycnogenol (French maritime pine bark extract) shown to improve menopause symptoms in new study
8. Crystal structure of archael chromatin clarified in new study
9. EU-funded study underlines importance of Congo Basin for global climate and biodiversity
10. University of Houston study shows BP oil spill hurt marshes, but recovery possible
11. Study demonstrates cells can acquire new functions through transcriptional regulatory network
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/25/2016)... 2016  Glencoe Software, the world-leading supplier of image ... will provide the data management solution OMERO Plus for ... Photo - ... Phenotypic analysis measures the characteristics and behavior ... between states such as health and disease, the presence ...
(Date:1/20/2016)...   MedNet Solutions , an innovative SaaS-based eClinical ... research, is pleased to announce the attainment of record-setting ... result of the company,s laser focus on (and growing ... it,s comprehensive, easy-to-use and highly affordable cloud-based technology platform. ... MedNet growth achievements in 2015 include: , ...
(Date:1/13/2016)... , January 13, 2016 ... the addition of the  "India Biometrics ... & Forecast (2015-2020)"  report to ... ) has announced the addition of ... Market - Estimation & Forecast (2015-2020)" ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... ... February 11, 2016 , ... Reichert ... years, continues today to pursue the highest level of accuracy and quality with ... AR9 Refractometer and the AR5 Refractometer. Accurate, reliable and tough enough for ...
(Date:2/10/2016)...  The Maryland House of Delegates and House Speaker ... of Maryland School of Medicine Dean E. Albert ... Medical System President and CEO Robert Chrencik , ... honor given to the public by the leader of ... and Mr. Chrencik for their contributions to our ...
(Date:2/10/2016)... 10, 2016  Allergan plc (NYSE: AGN ) ... Brent Saunders , Allergan,s CEO and President, will be ... session at the RBC Capital Markets Healthcare Conference on ... The New York Palace Hotel in New ... live and can be accessed on Allergan,s Investor Relations ...
(Date:2/10/2016)... , ... February 10, 2016 , ... ... to their comprehensive training and support program, Sonalinkā„¢ remote monitoring. The inaugural launch ... performed on Friday, February 5th, connecting Dr. Samuel Peretsman to a HIFU technical ...
Breaking Biology Technology: