Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene Mutation Exacerbates Eye Defect in Inherited Glaucoma

07.03.2003


While studying mice with a mutant gene whose counterpart causes inherited glaucoma in humans, researchers have discovered a second gene mutation that worsens the structural eye defect that causes this type of glaucoma.



The newly discovered gene mutation affects production of L-DOPA. The researchers suggest that it might be feasible to prevent glaucoma by administering L-DOPA, which is used in treating Parkinson’s disease.

The researchers, led by Howard Hughes Medical Institute investigator Simon W. M. John at The Jackson Laboratory, reported their findings in the March 7, 2003, issue of the journal Science. John’s colleagues included Richard Libby and Richard Smith of The Jackson Laboratory, and Frank Gonzalez of the National Cancer Institute.


In their studies in mice, the researchers explored how the absence of the gene that encodes the protein Cyp1b1 — the same defect that occurs in humans with primary congenital glaucoma (PCG) — affects development of glaucoma. In examining the mice, the scientists found malformations of ocular drainage structures that normally control pressure as the liquid aqueous humor flows out of the eyeball. These eye abnormalities are known as anterior segment dysgenesis.

According to Smith, who has treated patients with PCG, the ability to pinpoint the abnormalities in mice will most likely advance understanding of how the disease develops in humans. “The frustrating thing about attempting to understand human PCG is that there have been very few cases reported in which the patients haven’t already had glaucoma for many years and been subjected to surgery and multiple medications,” said Smith. “So, by the time we can examine the human tissue, the anatomic defect is very difficult to determine.”

According to John, these anatomic abnormalities are an underlying cause of the severe glaucoma that affects people with PCG. Although the disorder is relatively uncommon — occurring in about one in 10,000 births in the United States — it can cause devastating consequences, he said.

“If you have abnormalities or decreased functioning of the drainage structures, the input of aqueous humor can result in increased intraocular pressure and the very nasty glaucoma that human infants suffer,” he said. “This can be a painful condition with pressures high enough to tear the cornea and risk loss of vision.”

One puzzle confronting researchers, said John, is that some infants with the inherited condition can suffer serious glaucoma, while others either show delayed effects or none at all. “So, although it is not widely accepted, we believed that there could be multiple genetic and/or environmental factors that could affect the course of the disease,” he said. Such factors could interact with one another to compromise the intricate drainage structures to a greater degree in some cases than in others, said John.

A clue to one possible genetic factor arose from observations that albino mice lacking Cyp1b1 appeared to show worse pathology than pigmented mice. A series of genetic crosses of various mice by Libby and his colleagues produced strains of mice whose only difference was the presence or absence of pigmentation. The researchers ultimately pinpointed the key modifier of severity of glaucoma, showing that in the Cyp1b1-negative mice it hinged on the status of the gene that encodes the enzyme tyrosinase. The tyrosinase enzyme is involved in the pigmentation process as a key catalyst for converting the amino acid tyrosine to a precursor pigment molecule, L-DOPA.

The researchers also explored how mutations in the gene for tyrosinase affected mice lacking the FOXC1 gene, which also causes PCG and other forms of glaucoma in humans. They found that the tyrosinase-deficient FOXC1 mice also showed more severe abnormalities in their ocular drainage system.

To determine whether administering L-DOPA might alleviate these defects, the researchers administered the chemical to the drinking water of pregnant mice lacking both Cyp1b1 and tyrosinase. They found that the treatment prevented the severe abnormalities in pups born to the mice who had been fed L-DOPA.

John noted that another enzyme, tyrosine hydroxylase, is also involved in L-DOPA production, suggesting yet another biochemical pathway affecting anterior segment development in the eye and severity of PCG.

“Together, these findings open a new avenue for investigating the role of L-DOPA in anterior segment development and glaucoma caused by various genes,” said John. “Furthermore, identifying L-DOPA as a key molecule may link the functions of many of the known genes that cause anterior segment dysgenesis and glaucoma,” he said. “Most of these known genes can affect tyrosine hydroxylase in the neural crest cells, from which the relevant anterior segment structures derive. Therefore, our work provides a conceptual linkage for anterior segment developmental disorders caused by different genes, and it provides an important framework for future experiments.”

While the researchers note that L-DOPA is already used to treat symptoms of Parkinson’s disease, they are cautious about recommending its use in treating glaucoma. “L-DOPA is a molecule that affects the nervous system, and we need to proceed very carefully with further animal and human studies before we will know whether such a treatment can become a clinical reality,” said John.

It may be the case, said John, that drugs that enhance the enzyme tyrosinase itself — and not administration of L-DOPA — that will be more useful as therapeutics. “We are very excited because these findings open up a new avenue for research on these disorders,” he said.

Jim Keeley | Howard Hughes Medical Institute
Further information:
http://www.hhmi.org/news/john.html

More articles from Health and Medicine:

nachricht Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University

nachricht Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>