Featured Research

from universities, journals, and other organizations

Study Suggests Potential New Approach To Glaucoma Therapy

Date:
August 18, 1999
Source:
Washington University School Of Medicine
Summary:
Investigators at Washington University School of Medicine in St. Louis believe they have identified the basis for a new way to treat glaucoma, the second-leading cause of irreversible vision loss in the United States.

St. Louis, Aug. 17, 1999 -- Investigators at Washington University School of Medicine in St. Louis believe they haveidentified the basis for a new way to treat glaucoma, the second-leading cause of irreversible vision loss in the UnitedStates.

In the Aug. 17 issue of Proceedings of the National Academy of Sciences, the investigators report on experimentsinvolving an animal model of glaucoma. Working in rats with elevated eye pressure, they were able to prevent loss ofretinal ganglion cells by inhibiting the action of an enzyme that makes nitric oxide.

"Having seen reports on nerve damage caused by excessive nitric oxide, we decided to look for evidence of high levelsof nitric oxide in human eyes with glaucoma," said lead author Arthur H. Neufeld, Ph.D., the Bernard Becker ResearchProfessor of Ophthalmology and Visual Sciences. "Using sophisticated staining techniques, we detected an enzyme calledinducible nitric oxide synthase in the optic nerve head tissue of patients with glaucoma."

This enzyme — NOS-2 — can produce excessive amounts of nitric oxide, and Neufeld and colleagues regarded itspresence as evidence that nitric oxide might be involved with the ganglion cell damage seen in glaucoma. To explore thatidea, they set out to determine whether NOS-2 was causing the damage in retinal cells or appearing as a byproduct ofthat damage.

"We adopted an animal model of glaucoma that raises pressure levels in the eyes of rats," Neufeld said. "And we foundthat, as in humans, the eyes of rats with elevated pressure lost retinal ganglion cells and that the tissue also containedelevated levels of NOS-2."

For the last century, most medical and surgical therapies for glaucoma have attempted to lower pressure in the eye,aiming to prevent or delay damage to ganglion cells and preserve good vision. "But we have many clinical situationswhere we can’t get the pressure low enough to avoid damage," said Bernard Becker, M.D., professor emeritus andformer head of the Department of Ophthalmology and Visual Sciences. "In spite of the drugs we have, in spite of surgery,in spite of everything we try to do, the patient continues to lose vision."

Inhibiting NOS-2 may provide a new option. The investigators put a drug called aminoguanidine into the drinking waterof rats with elevated eye pressure. Other rats did not get the drug. After six months, the researchers found that theuntreated rats lost 36 percent of their retinal ganglion cells in the eyes with elevated intraocular pressure. Those whoreceived aminoguanidine lost less than 10 percent of their retinal ganglion cells in spite of continued elevated intraocularpressure.

"As the paper reports, there were marked changes in the eyes of animals that did not receive the drug," Neufeld said."But we didn’t seen that type of cell loss in animals that were treated with aminoguanidine. Statistically, the retinalganglion cell loss was not any different than in the controls."

Processes from retinal ganglion cells leave the eye through a structure called the optic disc, and ophthalmologists keep aclose watch on the optic disc in glaucoma patients. In this study, Becker did the same thing with the rats.

"Once a month, we looked into the animal eyes through an ophthalmoscope," he explained. "Patients with glaucomadevelop ‘cupping’ of the disc — a bowing back and atrophy of that structure. These rats also were developing thiscupping of the optic disc, but in those treated with aminoguanidine, no cupping occurred."

Although the rats treated with aminoguanidine had less damage in the retina and the optic nerve, their intraocular pressurewas no different than in animals that did not receive the drug. "That means aminoguanidine did not lower the elevatedpressure in these animals," Neufeld said. "That is important because it means that lowering the pressure is not whatprotected the retinal ganglion cells."

That fact gives the researchers hope that it may be possible to treat patients whose glaucoma does not respond topressure-lowering drugs or surgery, as well as a subset of patients who have what doctors call normal-pressureglaucoma. The hope is inhibitors of NOS-2 might preserve vision in those patients who don’t respond to currenttherapies and also could be used along with drugs that lower intraocular pressure.

"The emerging concept of using drugs to protect nerve cells is being aggressively pursued across the country," said CarlKupfer, M.D., director of the National Eye Institute, part of the National Institutes of Health, the federal agency thathelped fund the study. "New approaches to treating glaucoma are welcome, and this work will be followed closely byother glaucoma researchers."

Robert Ritch , M.D., agrees. He is chairman of the scientific advisory board of The Glaucoma Foundation, which alsohelped fund this project. "We’re getting closer to finding the answers," Ritch said. "Although the current investigations donot yet translate into clinical use, this is the sort of breakthrough research that could eventually lead to a stemming ofvision loss from glaucoma."

In an accompanying commentary article, Paul L. Kaufman. M.D., professor and Director of Glaucoma Services at theUniversity of Wisconsin-Madison, said the paper "will likely be considered a classic in years to come" and that thestudy’s conclusions may contribute to more than finding better treatments for glaucoma. "The significance of their findingsmay go far beyond glaucoma, with broad pathophysiologic and therapeutic implications for neurodegenerative andneurovascular diseases in general," Kaufman wrote.

For now, however, the research is focusing purely on glaucoma. In future animal studies, Neufeld and Becker will testother drugs that inhibit production of NOS-2. If their work progresses, human trials may follow.

###

This research was supported by grants from the National Eye Institute and the Glaucoma Foundation.

Neufeld AH, Sawada A, Becker B. Inhibition of Nitric Oxide Synthase-2 by Aminoguanidine Provides Neuroprotectionof Retinal Ganglion Cells in a Rat Model of Chronic Glaucoma. Proceedings of the National Academy of Sciences,vol. 96 (17), pp 9944-9948, Aug. 17, 1999.

Copies of the paper are available from the PNAS news office, (202) 334-2138, or email <pnasnews@nas.edu>.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Study Suggests Potential New Approach To Glaucoma Therapy." ScienceDaily. ScienceDaily, 18 August 1999. <www.sciencedaily.com/releases/1999/08/990818071333.htm>.
Washington University School Of Medicine. (1999, August 18). Study Suggests Potential New Approach To Glaucoma Therapy. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/1999/08/990818071333.htm
Washington University School Of Medicine. "Study Suggests Potential New Approach To Glaucoma Therapy." ScienceDaily. www.sciencedaily.com/releases/1999/08/990818071333.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
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