PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Researchers discover potential drug targets for early onset glaucoma

2014-01-24
(Press-News.org) Contact information: Brett Israel
brett.israel@comm.gatech.edu
404-385-1933
Georgia Institute of Technology
Researchers discover potential drug targets for early onset glaucoma

Using a novel high-throughput screening process, scientists have for the first time identified molecules with the potential to block the accumulation of a toxic eye protein that can lead to early onset of glaucoma.

Glaucoma is a group of diseases that can damage the eye's optic nerve and cause vision loss and blindness. Elevated eye pressure is the main risk factor for optic nerve damage.

Researchers have implicated a mutant form of a protein called myocilin as a possible root cause of this increased eye pressure. Mutant myocilin is toxic to the cells in the part of the eye that regulates pressure. These genetically inherited mutants of myocilin clump together in the front of the eye, preventing fluid flow out of the eye, which then raises eye pressure. This cascade of events can lead to early onset-glaucoma, which affects several million people from childhood to age 35.

To find molecules that bind to mutant myocilin and block its aggregation, researchers designed a simple, high-throughput assay and then screened a library of compounds. They identified two molecules with potential for future drug development to treat early onset glaucoma.

"These are really the first potential drug targets for glaucoma," said Raquel Lieberman, an associate professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology in Atlanta, whose lab led the research.

Lieberman presented her findings on January 20 at the Society for Laboratory Automation and Screening conference in San Diego, Calif.

The study was published on Nov. 26, 2013, in the journal ACS Chemical Biology. The National Institutes of Health and the Pew Scholar in Biomedical Sciences program provided support for the research. The work was a collaboration involving Georgia Tech, Emory University and the University of South Florida.

At the heart of the study was an assay that Lieberman's lab created to take advantage of the fundamental principles of ligand binding. In their assay, mutant myocilin is mixed with a fluorescent compound that emits more light when the protein is unwound. When a molecule from the library screen binds to myocilin, the pair becomes highly stable – tightly wound – and the fluorescent light emitted decreases. By measuring fluorescence, researchers were able to identify molecules that bound tightly to mutant myocilin.

The researchers then added these molecules to cultured human cells that were making the toxic aggregating myocilin. Treating the cells with the newly identified molecules blocked the aggregation and caused the mutated version of myocilin to be released from the cells, reducing toxicity.

"We found two molecules from that initial screen that bound to our protein and also inhibited the aggregation," Lieberman said. "When we saw that these compounds inhibited aggregation then we knew we were onto something good because aggregation underlies the pathogenesis of this form of glaucoma."

In a separate study, Lieberman's lab characterized the toxic myocilin aggregates. That study was published in December 2013 in the Journal of Molecular Biology. The study found that myocilin aggregates are similar to the protein deposits called amyloid, which are responsible for Alzheimer's disease and other neurodegenerative diseases.

"In Alzheimer's disease, the deposits are extracellular and kill neurons. In glaucoma the aggregates are not directly killing neurons in the retina to cause vision loss, but they are cytotoxic in the pressure-regulating region of the eye," Lieberman said. "It's parallel to all these other amyloids that are out there in neurodegenerative disease."

The researchers are now focusing on mapping the structure of myocilin to learn more about what myocilin does and why it is in the eye in the first place.

"The underlying problem with myocilin is that for 14 years it has been studied and still nobody really knows what its biological role is inside the eye," Lieberman said.



INFORMATION:

This research is supported by the National Institutes of Health (NIH) under award numbers RO1EY021205 and RO1NS073899, and the Pew Scholar in Biomedical Sciences program. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.

CITATION: Susan D. Orwig, et al., "Ligands for glaucoma-associated myocilin discovered by a generic binding assay," (ACS Chemical Biology, November 2013). (http://dx.doi.org/10.1021/cb4007776).

CITATION: Shannon E. Hill, et al., "The glaucoma-associated olfactomedin domain of myocilin forms polymorphic fibrils that are constrained by partial unfolding and peptide sequence," (Journal of Molecular Biology, December 2013). (http://dx.doi.org/10.1016/j.jmb.2013.12.002).



ELSE PRESS RELEASES FROM THIS DATE:

National plan for preventing healthcare-associated infections shows progress

2014-01-24
Philadelphia, Pa. (January 23, 2014) – Independent evaluators have found that measurable ...

The lung microbiome: A new frontier in pulmonary medicine

2014-01-24
The Annals of the American Thoracic Society has released a comprehensive supplement on the 56th annual Thomas L. Petty Aspen Lung Conference entitled "The Lung Microbiome: A New Frontier in Pulmonary Medicine." ...

Moderate doses of radiation therapy to unaffected breast may prevent second breast cancers

2014-01-24
NEW YORK, NY (January 23, 2014) — Survivors of breast cancer have a one in ...

Johns Hopkins scientists identify a key to body's use of free calcium

2014-01-24
Scientists at Johns Hopkins report they have figured out a key step in how "free" calcium — the kind not contained in bones — is managed in the body, a finding that could aid in the development of ...

Liars find it more rewarding to tell truth than fib when deceiving others

2014-01-24
TORONTO, ON – A University of Toronto report based on two neural imaging studies that monitored brain activity has found individuals are more satisfied to get a reward from telling the truth rather ...

Happy 10th anniversary Opportunity!

2014-01-24
PUBLIC RELEASE DATE: 23-Jan-2014 [ | E-mail ] var addthis_pub="eurekalert"; var addthis_options = "favorites, delicious, digg, facebook, twitter, google, newsvine, reddit, slashdot, stumbleupon, buzz, more" Share Contact: Diana Lutz dlutz@wustl.edu 314-935-5272 Washington University in St. Louis Happy 10th anniversary Opportunity! Whirlwind tour of the past 10 years of adventures and discoveries by mission scientist Ray Arvidson VIDEO: Ray Arvidson, deputy ...

CWRU study finds depression symptoms and emotional support impact PTSD treatment progress

2014-01-24
Many individuals with posttraumatic stress disorder (PTSD) also experience depression. Researchers at Case Western Reserve University found that during PTSD treatments, ...

Sports medicine physical of the future could help athletes 'ESCAPE' sudden cardiac death

2014-01-24
BOSTON (01/23/14)—A young athlete in seemingly excellent health dies suddenly from a previously ...

Are developing heart valves sensitive to environmental chemicals?

2014-01-24
Baltimore, MD—Exposure to environmental endocrine disrupters, such as bisphenol A, which mimic estrogen, is associated with adverse health effects. Bisphenol A is commonly found in plastic bottles ...

New clues may link hereditary cancer genes to increased risk of cancer from alcohol

2014-01-24
In laboratory experiments conducted on human cell lines at the Johns Hopkins Kimmel Cancer Center, scientists have shown that people carrying certain mutations in two hereditary ...

LAST 30 PRESS RELEASES:

Study unexpectedly finds living in rural, rather than urban environments in first five years of life could be a risk factor for developing type 1 diabetes

Editorial urges deeper focus on heart-lung interactions in pulmonary vascular disease

Five University of Tennessee faculty receive Fulbright Awards

5 advances to protect water sources, availability

OU Scholar awarded Fulbright for Soviet cinema research

Brain might become target of new type 1 diabetes treatments

‘Shore Wars:’ New research aims to resolve coastal conflict between oysters and mangroves, aiding restoration efforts

Why do symptoms linger in some people after an infection? A conversation on post-acute infection syndromes

Study reveals hidden drivers of asthma flare-ups in children

Physicists decode mysterious membrane behavior

New insights about brain receptor may pave way for next-gen mental health drugs

Melanoma ‘sat-nav’ discovery could help curb metastasis

When immune commanders misfire: new insights into rheumatoid arthritis inflammation

SFU researchers develop a new tool that brings blender-like lighting control to any photograph

Pups in tow, Yellowstone-area wolves trek long distances to stay near prey

AI breakthrough unlocks 'new' materials to replace lithium-ion batteries

Making molecules make sense: A regional explanation method reveals structure–property relationships

Partisan hostility, not just policy, drives U.S. protests

The Journal of Nuclear Medicine Ahead-of-Print Tip Sheet: August 1, 2025

Young human blood serum factors show potential to rejuvenate skin through bone marrow

Large language models reshape the future of task planning

Narrower coverage of MS drugs tied to higher relapse risk

Researchers harness AI-powered protein design to enhance T-cell based immunotherapies

Smartphone engagement during school hours among US youths

Online reviews of health care facilities

MS may begin far earlier than previously thought

New AI tool learns to read medical images with far less data

Announcing XPRIZE Healthspan as Tier 5 Sponsor of ARDD 2025

Announcing Immortal Dragons as Tier 4 Sponsor of ARDD 2025

Reporting guideline for chatbot health advice studies

[Press-News.org] Researchers discover potential drug targets for early onset glaucoma