Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Develop Animal Model for TB-Related Blindness

19.12.2011
Working with guinea pigs, tuberculosis experts at Johns Hopkins and elsewhere have closely mimicked how active but untreated cases of the underlying lung infection lead to permanent eye damage and blindness in people.

Lead study investigator and Johns Hopkins infectious disease specialist Petros Karakousis, M.D., says the new animal model should hasten development of a badly needed, early diagnostic test for the condition. Symptoms of ocular TB — vision loss, and redness and pain in the eye — are often indistinguishable from symptoms of other chronic infections and inflammatory conditions, including toxoplasmosis and sarcoidosis, which can often lead to selecting the wrong therapy.

“TB infection can be active in the eyes even in the absence of lung symptoms,” says Karakousis, an assistant professor at the Johns Hopkins University School of Medicine. “So, there are usually long delays in diagnosis, and by this time, it’s too late for tens of thousands of people who are already going blind due to permanent inflammatory damage to the inner lining of the eyes.”

The scenario, he noted, is especially true in the United States and Europe, where TB is far less common than in developing countries, where most of the 9 million new infections occur each year. Most new cases in the United States occur in people whose immune systems are already depressed from co-infection with HIV and who lack access to antibiotic treatments. Some 20 percent of people with the potentially deadly lung infection, caused by Mycobacterium tuberculosis, develop inflammation in other organs, including in the inner tissue linings of the eye or linings surrounding the brain.

The Johns Hopkins team’s description of the animal model for ocular TB appeared in the Public Library of Science One online last week.

Karakousis says a clear and rapid test for ocular TB would not only prevent treatment delays, but also reduce the rate of misdiagnosis. Suspected inflammatory disease, such as sarcoidosis and lupus in the eye, are treated with steroids, which can promote bacterial spread across other body organs, making the infection worse.

Current diagnostic methods for ocular TB involve a lot of guesswork, says Karakousis. Underlying signs of active TB in the lungs, such as positive chest X-rays and sputum samples, are helpful in making a diagnosis but often not present. Tissue biopsy of the affected part of the eye offers more reliable confirmation of infection, but the procedure involves painful needle extraction that carries the risk of permanent eye damage, even blindness. Physicians are often deciding to treat based on a high suspicion of TB infection, and then taking a “wait and see” approach for several weeks or months to determine if people are getting well or not.

Karakousis and his team used small, aerosolized doses of about 200 bacteria to infect each animal’s lungs, a procedure closely replicating human TB infection, which is spread when uninfected people inhale small numbers of the organisms coughed up by people already infected. Karakousis says all previous animal models for studying TB infection, in mice and in rabbits, used more than 10 times larger doses of injected tubercle organisms to eventually infect the eyes, which is not really how the disease spreads to the eyes.

Microscopic testing of eye tissue samples showed all guinea pigs were infected with TB after two months, and that the disease spread through the bloodstream, as it does in humans.

Moreover, small, grainy nodules, a telltale sign of active TB infection, were observed in both the lungs and in the inner choroid tissue layer lining the eyes. Some choroidal tissue death and thickening, as well as bleeding from blood vessels, were also seen — all known indicators of active TB infection in humans.

Further tissue analysis of lung and eye granulomas revealed increased production of vascular endothelial growth factor, or VEGF, a signaling protein linked to irregular blood vessel formation and known to play a role in other vascular-related vision problems, such as blindness due to diabetes and age-related macular degeneration.

Karakousis says ophthalmologists have already had some success with VEGF antibody treatments, used in combination with standard antibiotics, to treat TB infection in the eyes and the lungs. He adds that anti-VEGF drugs could represent new therapies for ocular-TB-related disease and that VEGF levels in the eye could signal active TB infection in the eye. The Johns Hopkins team next plans to test VEGF and other protein levels in eye fluid as possible diagnostic test markers for ocular TB.

“Having a verifiable diagnostic test for ocular TB is key to picking up on active infections early and providing treatment that stands the best chance of preventing long-term damage, with our without any signs or symptoms of lung infection,” says Karakousis. “Until then, physicians will have to be aware to test for ocular TB, especially in regions like Africa and Southeast Asia where the disease remains endemic, and to listen for clues in the patient’s life history that might alert them to earlier possible TB exposure.”

TB is the leading cause of death among people co-infected with HIV, the virus that causes AIDS, and is responsible for an estimated 2 million deaths annually, including a half-million in those infected with both organisms.

In addition to Karakousis, Seema Thayil, Ph.D., was another Johns Hopkins researcher involved in the study, conducted from June 2010 to June 2011. Other investigators were Thomas Albini, M.D.; Andrew Moshfeghi, M.D., M.B.A.; and Jean-Marie Parel, Ph.D., from the Bascom Palmer Eye Institute at the University of Miami, Florida; and Hossein Nazari, M.D.; and Narsing Rao, M.D., from the Doheny Eye Institute, at the University of Southern California in Los Angeles.

For additional information, go to:
http://www.hopkinsmedicine..org/dom/tb_lab/
http://www.hopkinsmedicine.org/DOM/TB_Lab/faculty/Karakousis.html
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028383

David March | Newswise Science News
Further information:
http://www.jhmi.edu

More articles from Health and Medicine:

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>