Featured Research

from universities, journals, and other organizations

Nature's Own Medicine For Vision Loss: Inhibitor Of Angiogenesis Found By Biologists At The Scripps Research Institute

Date:
January 3, 2002
Source:
Scripps Research Institute
Summary:
A potentially potent inhibitor of angiogenesis, the process whereby new blood vessels are formed from existing ones, can be found in one of the very molecules involved in the same process. This finding, made by two scientists from The Scripps Research Institute (TSRI), may lead to new therapies, as abnormal angiogenesis is the leading cause of vision loss in the United States.

A potentially potent inhibitor of angiogenesis, the process whereby new blood vessels are formed from existing ones, can be found in one of the very molecules involved in the same process. This finding, made by two scientists from The Scripps Research Institute (TSRI), may lead to new therapies, as abnormal angiogenesis is the leading cause of vision loss in the United States.

In the current issue of the journal Proceedings of the National Academy of Sciences, two reports by collaborating authors from TSRI describe the antiangiogenesis activity of a fragment of the human protein tryptophanyl-tRNA synthetase (TrpRS). The reports are authored by Paul Schimmel, Ph.D., Ernest and Jean Hahn Professor, Chair of Molecular Biology and Chemistry, and member of The Skaggs Institute for Chemical Biology and Martin Friedlander, M.D., Ph.D., Associate Professor in the Department of Cell Biology and Chief of the Retina Service in the Division of Ophthalmology, Department of Surgery at Scripps Clinic.

"There are many potential applications [for TrpRS], ranging from blindness to cancer, that we want to pursue," says Schimmel.

Angiogenesis is a natural biological process that can sometimes go awry. Abnormal angiogenesis is the cause of age-related macular degeneration (ARMD) and diabetic retinopathy, diseases that afflict tens of millions of Americans and cause catastrophic vision loss in many.

Both of these eye diseases are characterized by the development of abnormal blood vessel growth in the eye. In the case of ARMD, new blood vessels grow under the retina. In diabetic retinopathy, abnormal vessels grow on top of the retina. The effect is much the same; the vessels interfere with normal structures or the transmission of light to the back of the eye, impeding vision. There is currently no effective treatment for the vast majority of these patients.

There are several antiangiogenic compounds in clinical trials. But TrpRS, says Friedlander, appears to be more potent.

"People typically talk about 20, 30, 40 percent inhibition [of new vessel formation] for the compounds that are in clinical trials," says Friedlander. "What we have seen in our pre-clinical studies is that in 70 percent of cases, you get 100 percent inhibition."

The fact that TrpRS is a naturally occurring protein may make it an even more effective treatment because it will not have the same problems of toxicity and immunogenicity that plague some other potential drugs.

"Moreover," says Friedlander, "this is something that we can teach the cell how to make." One clinical approach to treating angiogenic vision loss, he says, could be to deliver the TrpRS molecules directly into the eye through gene- and cell-based vectors.

These are applied questions that Friedlander and Schimmel are just beginning to explore. At the same time, they are pursuing the basic science questions of the mechanisms and evolutionary meaning behind TrpRS inhibition of angiogenesis.

Cells undergo proliferation of blood vessels as a response to inflammation, infection, or ischemic blockage of blood flow. The raw material for this proliferation is the proteins cells express through their genes.

After a gene is transcribed from double-stranded DNA into a single-stranded form of RNA called messenger RNA (mRNA), a large molecule called the ribosome translates the mRNA into a protein. The ribosome recognizes another type of molecule, transfer RNA (tRNA), which brings the ribosome the amino acids from which it constructs proteins.

One of the first steps of protein synthesis involves "charging" the tRNA molecules with the amino acids, and this step is carried out by a set of molecules known as tRNA synthetases. TrpRS, for instance, charges tRNA molecules with the amino acid tryptophan. Since protein synthesis provides the raw material during angiogenesis, molecules like TrpRS play a big role.

Interestingly, two naturally occurring, shortened forms of the molecule have proven to be powerful inhibitors of angiogenesis. These truncated forms are either made after one end of the full-size TrpRS is chopped off by proteolysis or they are synthesized from an "alternatively spliced" mRNA, which has been rearranged by the cell before the ribosome uses it to make a protein.

This dual role for TrpRS surprised Schimmel and Friedlander, because they did not expect a molecule involved in protein synthesis and cell proliferation to be involved in shutting down that same proliferation.

In nature, TrpRS could be controlling the direction and perhaps the termination of blood vessels, and organisms may have evolved to use the shortened form of TrpRS to regulate angiogenesis because the full-size protein was already at the site of proliferation.

"We're trying hard to figure out what role [the alternatively-spliced fragment] plays in nature," says Schimmel. "The key thing that we have to do now is identify its receptor."

The research article "A human aminoacyl-tRNA synthetase as a regulator of angiogenesis" is authored by Keisuke Wakasugi, Bonnie M. Slike, John Hood, Atushi Otani, Karla L. Ewalt, Martin Friedlander, David Cheresh, and Paul Schimmel and appears in the January 2, 2002 online issue of Proceedings of the National Academy of Sciences.

The research article "A fragment of human TrpRS as a potent antagonist of ocular angiogenesis" is authored by Atushi Otani, Bonnie M. Slike, Michael I. Dorrell, John Hood, Karen Kinder, Karla L. Ewalt, David Cheresh, Paul Schimmel, and Martin Friedlander and appears in the January 2, 2002 online issue of Proceedings of the National Academy of Sciences.

The research was funded by the National Eye Institute, The National Cancer Institute, The Skaggs Institute for Chemical Biology, The Robert Mealey Program for the Study of Macular Degenerations, the ARCS Foundation, and the National Foundation for Cancer Research.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Cite This Page:

Scripps Research Institute. "Nature's Own Medicine For Vision Loss: Inhibitor Of Angiogenesis Found By Biologists At The Scripps Research Institute." ScienceDaily. ScienceDaily, 3 January 2002. <www.sciencedaily.com/releases/2002/01/020103074421.htm>.
Scripps Research Institute. (2002, January 3). Nature's Own Medicine For Vision Loss: Inhibitor Of Angiogenesis Found By Biologists At The Scripps Research Institute. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2002/01/020103074421.htm
Scripps Research Institute. "Nature's Own Medicine For Vision Loss: Inhibitor Of Angiogenesis Found By Biologists At The Scripps Research Institute." ScienceDaily. www.sciencedaily.com/releases/2002/01/020103074421.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins