Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transport interrupted -- Texas A&M biologists trace cause of early blindness to tissue defect

12.03.2007
Researchers at Texas A&M University are shedding light on a rare form of early blindness, identifying the cells involved and paving the way for possible therapies to treat or even prevent what is currently an incurable disease.

The findings, funded by Fight for Sight and the National Institutes of Health, are published in the March 5-9 online Early Edition (EE) of the Proceedings of the National Academy of Sciences.

Since his post-doctoral days at Harvard University, Texas A&M biologist Dr. Brian Perkins has been studying protein transport within photoreceptors—the rod and cone cells that allow organisms to detect their visual worlds—in zebrafish, a vertebrate whose eye physiology is essentially identical to that of a human. Recently he became intrigued by a 30-year-old debate involving photoreceptor death—specifically, whether it was a cause or an effect—in choroideremia, an X chromosome-linked hereditary retinal degenerative disease that leads to blindness in an estimated one in every 100,000 people, beginning with severe loss of vision and night blindness as early as the pre-teen years and progressing to complete blindness by middle age.

Using a line of mutant zebrafish developed by Rockefeller University’s Jim Hudspeth, Perkins and Texas A&M biology graduate student Bryan Krock zeroed in on a specific protein, the Rab escort protein-1 (REP1), which helps regulate intracellular traffic in the photoreceptors as well as a neighboring tissue called the retinal pigment epithelium (RPE). In collaboration with the University of Western Kentucky’s Joseph Bilotta, they observed that mutations in REP1 disrupt cellular processes in the RPE, causing photoreceptor death as a secondary consequence. Their results suggest therapies that correct the RPE may successfully rescue photoreceptor loss in choroideremia and even reverse the disease.

... more about:
»Perkins »RPE »photoreceptor »zebrafish

"For decades, no one knew if the photoreceptors were dying because of an internal trafficking defect or if they were dying as a secondary consequence of problems in the RPE," Perkins explains. "Previous research based on studies of human tissue said it was independent of the RPE. We wanted to see if that hypothesis was true. It turns out that it wasn’t, but in making the wrong assumption, we found out something even more interesting—a different way to cause photoreceptor death."

"If you disrupt protein transport, you kill the cell," Perkins notes. "In this case, the transportation process in the photoreceptors was perfectly normal, but the neighboring RPE was defective, which is why the photoreceptors were dying."

"For this particular disease, we now have the reason why people go blind. If our results translate into treating humans, it should lead to design of potential therapies. But at the very least, it helped settle the controversy of why photoreceptors are failing and why people go blind. Knowing the right cell type to target is half the battle, and we’re saying it’s the RPE, not the photoreceptor, and that the functional gene can potentially be added back to the RPE using gene therapy."

In addition to being small, relatively inexpensive and suitable for large-scale genetic experiments, zebrafish make ideal research specimens in Perkins’ eyes because they are model systems, both for treating human disease and for determining what’s important.

"Most people think of mice, monkeys and other furry animals, rather than fish, when they think of research subjects for human diseases," Perkins says. "An advantage of zebrafish is the ability to inexpensively perform forward genetic screens. Using chemicals, we can induce random mutations throughout the genome. We then search through dozens of zebrafish families to identify mutant zebrafish with traits that resemble human diseases. We use the screen to look for specific traits we think are important, but we can’t pre-select the gene that caused it."

"Rather than starting with a gene to mutate and hoping to generate a given trait, we select for the trait, then go find the mutated gene that caused it. We let nature and the organism tell us what’s important and what’s not."

Perkins says the next steps for his laboratory involve continuing investigation into protein transport processes and trying to find additional zebrafish models of photoreceptor-specific mutations that lead to additional causes of retinal degeneration and blindness.

Shana K. Hutchins | EurekAlert!
Further information:
http://www.tamu.edu
http://www.bio.tamu.edu/FACMENU/FACULTY/perkins.htm
http://www.pnas.org/cgi/content/abstract/0605818104v1

Further reports about: Perkins RPE photoreceptor zebrafish

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>