Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune cell age plays role in retinal damage in age-related macular degeneration

05.11.2007
Studying a mouse model of age-related macular degeneration, the leading cause of blindness in older Americans, scientists at Washington University School of Medicine in St. Louis have found age is key in determining whether damaging blood vessels will form beneath the retina and contribute to vision loss.

The scientists discovered that specific immune cells called macrophages play a role in the disease process in older mice by failing to block the development of abnormal, leaky blood vessels behind the retina. But in younger mice, macrophages typically prevent abnormal blood vessel formation.

The scientists believe better understanding of how macrophages work may provide potential targets for therapies to slow or even reverse vision loss. The findings are reported in the November issue of the Journal of Clinical Investigation.

Age-related macular degeneration is the leading cause of blindness in the United States in people over the age of 50. It accounts for more than 40 percent of blindness among the elderly in nursing homes, and as baby boomers get older, the problem is expected to grow, with at least 8 million cases predicted by the year 2020.

Whether the macrophages will block or encourage the growth of damaging blood vessels is related to the subtype of macrophage according to principal investigator Rajendra S. Apte, M.D., Ph.D., assistant professor of ophthalmology and visual sciences.

"There are two basic types of macrophages — known as M1 and M2 — and in the older mice, there was a preponderance of cells with the M2 signature," he says. "These M2 cells promoted abnormal blood vessel growth in the eyes of older mice. In younger mice, most macrophages had the M1 signature, and those cells inhibited the development of defective blood vessels."

Apte says it appears the population of macrophages drifts from the M1 type to M2 cells because of an increase in the levels of an immune system molecule called interleukin-10 (IL-10) in the eye as the mice get older. In a previous study, his team had found that high levels of IL-10 interfere with macrophages' ability to regulate blood vessel growth. As mice got older, the animals made more IL-10, and this caused more macrophages to become the M2 type.

"The older mice had much higher levels of IL-10," Apte explains. "That suggests IL-10 may be driving this process because higher IL-10 levels are associated with more M2 macrophages that cannot regulate blood vessel growth, and lack of IL-10, as in genetic knockout mice, leads to a preponderance of M1 macrophages."

The blood vessels that form in age-related macular degeneration are not like the mature vessels found in most of the body. Vessels associated with the disease don't have normal, tight junctions, but rather leak and bleed. They also tend to be located beneath the macula, the center of the retina, and when they bleed, the result is loss of vision.

Just as there are two types of macrophages, there also are two types of macular degeneration: a "dry" form and a "wet" form. Most patients have the dry form of the disease, which sometimes can progress and cause severe vision loss. But between 80 and 90 percent of blindness occurs in the wet form of the disease and is caused by abnormal blood vessel growth beneath the retina.

Apte's team studied both young and old mice whose eyes were treated with a laser that spurs the growth of the damaging blood vessels. Although the acute laser injury is not identical to the chronic damage caused by the disease, Apte says the animal model has been remarkably successful in identifying therapies to treat the blinding eye disease.

Some of the laser-treated mice could not make IL-10. Previously, Apte's team found that mice genetically engineered without IL-10 develop fewer abnormal vessels beneath the retina. That also was true in this study. One reason may be that mice without IL-10 have mostly M1 macrophages, which inhibit new blood vessel formation.

It may be true, Apte says, that as people age, they experience increases in IL-10 levels, as well as other cytokines that influence a drift towards M2 macrophages just as the mice do. It's also possible that factors such as smoking, uncontrolled high blood pressure or a genetic pre-disposition may enhance this process.

"It appears from the mice we've studied that the microenvironment in and around the eye might influence how macrophages behave and what subclass of macrophages is likely to be present," Apte says. "We believe this cascade involving IL-10 and macrophages provides potential targets for therapies to prevent some of the devastating vision loss that affects so many patients with age-related macular degeneration and may even be useful in treating other diseases that involve abnormal blood vessel growth, such as cancer and heart disease."

Jim Dryden | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Hubble captures massive dead disk galaxy that challenges theories of galaxy evolution

22.06.2017 | Physics and Astronomy

New femto-camera with quadrillion fractions of a second resolution

22.06.2017 | Physics and Astronomy

Rice U. chemists create 3-D printed graphene foam

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>