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Zebrafish study may point way to blindness cure

 

By Ben Hirschler Wed Aug 1, 2:25 AM ET

 

 

 

LONDON (Reuters) - The ability of zebrafish to regenerate damaged retinas has

given scientists a clue about restoring human vision and could lead to an

experimental treatment for blindness within five years.

 

British researchers said on Wednesday they had successfully grown in the

laboratory a type of adult stem cell found in the eyes of both fish and mammals

that develops into neurons in the retina.

 

In future, these cells could be injected into the eye as a treatment for

diseases such as macular degeneration, glaucoma and diabetes-related blindness,

according to Astrid Limb of University College London's (UCL) Institute of

Ophthalmology.

 

Damage to the retina -- the part of the eye that sends messages to the brain

-- is responsible for most cases of sight loss.

 

" Our findings have enormous potential, " Limb said. " It could help in all

diseases where the neurons are damaged, which is basically nearly every disease

of the eye. "

 

Limb and her colleagues studied so-called Mueller glial cells in the eyes of

people aged from 18 months to 91 years and found they were able to develop them

into all types of neurons found in the retina.

 

They were also able to grow them easily in the lab, they reported in the

journal Stem Cells.

The cells have already been tested in rats with diseased retinas, where they

successfully migrated into the retina and took on the characteristics of the

surrounding neurons. Now the team is working on the same approach in humans.

 

" We very much hope that we could do autologous transplants within five years, "

Limb told Reuters.

 

Autologous transplants, initially on a trial basis, will involve manipulating

cells and injecting them back into an individual's own eye. Eventually, Limb

hopes it will also be possible to transfer the cells between different people.

 

" Because they are so easy to grow, we could make stem cell banks and have cell

lines available to the general population, subject to typing as with blood

transfusions, " she said.

Just why zebrafish have an abundant supply of adult stem cells to regenerate

their retinas, while they are rare in mammals, remains a mystery but Limb

suspects it is because mammals have a limiting system to stop proliferation.

 

The new work on Mueller glial cells is the latest example of researchers

exploring the potential of different kinds of stem cells in treating eye

disease. Another team from UCL and Moorfield's Eye Hospital said in June they

aimed to repair damaged retinas with cells derived from embryonic stem cells.

 

http://news./s/nm/20070801/hl_nm/blindness_fish_dc

 

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Source: Rice University August 1, 2007 More on:

Developmental Biology, Human Biology, Genes, Gene Therapy, Genetics, Life

Sciences

 

Zebrafish Research Provides Answers About Neurological Development Science

Daily — Zebrafish cost about a dollar at the pet store. They grow from eggs to

hunting their own food in three days. Adults can lay up to 500 eggs at once...

and you have more in common with them than you think.

 

" For all their differences, humans and zebrafish aren't that dissimilar, " said

Rice University zebrafish expert Mary Ellen Lane. " For every zebrafish gene we

isolate, there is a related gene in humans. "

 

In her most recent work, Lane, graduate students Catherine McCollum and Shivas

Amin, and undergraduate Philip Pauerstein zeroed in on a gene called LMO4 that's

known to play roles in both cell reproduction and in breast cancer. Using the

tools of biotechnology, the team studied zebrafish that couldn't transcribe the

LMO4 gene, and they observed marked enlargement in both the forebrain and

optical portions of the embryos.

 

 

When they overexpressed the LMO4 gene, making more protein than normal, those

same areas shrank. " The study suggests that LMO4 independently regulates two

other genes that promote growth in those areas of the embryo, " said Lane,

assistant professor of biochemistry and cell biology. " It fills in another piece

of the bigger picture of what's going on during neurological development. "

 

Zebrafish -- like rats and fruit flies before them -- are becoming regular

contributors on research ranging from cancer to cocaine addiction. For example,

zebrafish were used a landmark 2005 study that led scientists to the human gene

that regulates skin color.

 

Lane's zebrafish studies explore one the major unexplained areas in

developmental biology -- how the brain and central nervous system develop. It

helps that zebrafish embryos grow from just a single cell to having a forebrain,

hindbrain, spinal column and eye within a scant 24 hours. It also helps that the

embryos are transparent and develop outside their mothers' bodies -- and can

thus been seen under a microscope at every step of their development.

" It's a beautiful organism for experiment, " Lane said. " It develops in a very

regular way, so any abnormality is easy to spot, even for undergraduates with

only a few days training. "

The study will appear later this year in the journal Developmental Biology.

 

Note: This story has been adapted from a news release issued by Rice

University.

http://www.sciencedaily.com/releases/2007/07/070730111642.htm

 

--

 

Public release date: 30-Jul-2007

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Contact: Justin Walden

jawalden

570-271-8083

Geisinger Health System

 

Geisinger scientist seeks cure for Lou Gehrig's disease, creating device to

find treatment Researcher teams with college students DANVILLE- A small

tropical fish, the curiosity of a Geisinger research scientist and some college

students have created the perfect storm of sorts in an attempt to find a cure

for one of the world’s most devastating neurological diseases.

 

On initial glance, there doesn’t seem to be much in common between zebrafish,

researcher Glenn S. Gerhard, MD and a trio of Bucknell University biomedical

engineering students. Yet they’re each playing a critical role in clearing a

major roadblock in the search for a cure for Lou Gehrig's disease.

 

Lou Gehrig's disease-or ALS or amyotrophic lateral sclerosis— is a fatal

neurodegenerative condition that affects nerve cells in the brain and the spinal

cord. As many as 20,000 Americans suffer from ALS and about 5,000 people in the

U.S. are diagnosed with the disease each year, according to the National

Institutes of Health.

 

It’s an aging-related disease that has long fascinated Gerhard, a staff

scientist in Geisinger’s Weis Center for Research.

 

Gerhard believes that the cure for the disease—or at least a more viable

treatment option—can be found in the right mix of the millions of drugs and drug

compounds that have been developed in laboratories across the world.

 

“There are so many different compounds but you don’t know which ones to test,”

Gerhard says. “We need bioengineering help to automate this process.”

 

That’s why Gerhard turned to the zebrafish and Bucknell University professor

Joe Tranquillo and students Erica Andreozzi, Meredith Kalman and Emily Thiel.

 

Several years ago, Gerhard started using the zebrafish, which can be easily

bred and tends to exhibit disease’s effects at an accelerated rate.

 

Yet the instruments needed to use these small and inexpensive fish for finding

new drugs have not yet been brought to market.

 

The students have developed a working prototype screening plate that allows

scientists to quickly expose zebrafish to ALS and mix chemicals together.

 

What once took weeks or months to screen thousands of potential cure-carrying

chemical solutions may soon take days, and with far fewer research staff

involved. A streamlined screening process will free up precious resources in the

lab, Gerhard says.

 

The Bucknell students worked throughout the spring semester to improve on

their design.

“In their first three years, Bucknell biomedical engineering students compile

an excellent set of technical and design skills through a number of open-ended

experiences,” Tranquillo says. “But they truly become engineers in their senior

year when they meet with a medical professional, identify a real problem and

spend a year solving that problem. The rich and educational interactions between

Dr. Gerhard, Erica, Meredith and Emily were extraordinary to witness. ”

 

Geisinger Ventures, which is the health system’s corporate development arm,

arranged the partnership between Gerhard and the Bucknell team.

 

Ventures is now seeking a corporate partner willing to license the invention

for production and distribution.

 

Geisinger Ventures nurtures innovative ideas, licenses and brings to market

intellectual property, develops business plans, and catalyzes growth of

for-profit companies. Gerhard’s work fits perfectly into Geisinger Ventures’

mission, says director Bryan Allinson.

“Ventures-worthy ideas generally are focused on a better way to use a device,

a piece of equipment or a process,” Allinson says. “The work with zebrafish has

the potential to identify therapeutics that could help the thousands of people

who suffer from ALS.”

 

In the disease’s early stage, symptoms may be so hard to detect that the

disease gets overlooked. But by the end stages of the disease, the patients are

totally paralyzed.

“ALS is a terrible disease,” Gerhard says. “Your brain is fine but your body

and your muscles just waste away.”

 

http://www.eurekalert.org/pub_releases/2007-07/ghs-gss073007.php

 

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