Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCLA researchers identify key enzyme linked to childhood blindness

12.08.2005


Findings could lead to gene therapy cure



In findings that could lead to curing some forms of congenital blindness through gene therapy, researchers at UCLA have discovered that RPE65, a gene missing in infants born with the blinding disease Leber congenital amaurosis, is also a key enzyme in the visual cycle. The identity of this enzyme has long been a mystery to scientists.
The study, "Rpe65 is the Retinoid Isomerase in Bovine Retinal Pigment Epithelium," is published in the Aug. 12 issue of Cell magazine.

"We were amazed when we discovered the function for Rpe65 -- and that Rpe65 is the retinoid isomerase. It is a protein that all of us had known about for years," said Dr. Gabriel Travis, professor of ophthalmology and biological chemistry at UCLA’s Jules Stein Eye Institute and one of the researchers. "It’s like searching the world for a treasure, then discovering it in your own back yard."



Leber congenital amaurosis is an inherited disease that is believed to cause up to 20 percent of all cases of childhood blindness. It is caused by mutations in several different genes including RPE65. An important characteristic of this disease is that the light sensitive rod and cone cells remain intact in the retinas of Leber patients for a long time.

"This suggests that replacement of RPE65 by gene therapy should correct the blindness in these children, as was observed in mice and dogs with RPE65 mutations," Travis said. "This is a major breakthrough in understanding the visual cycle. It has ramifications for several inherited blinding diseases caused by mutations in visual cycle genes."

The newly identified isomerase enzyme plays a crucial role in the regeneration of rhodopsin visual pigment in the retina after light exposure. Rhodopsin contains a light absorbing molecule called 11 cis retinaldehyde, related to vitamin A, which is converted upon light absorption to all trans retinaldehyde in a process called photo bleaching. This conversion is the first step in visual perception.

Photo bleaching leaves the rhodopsin insensitive to light until the all trans retinaldehyde is converted, or "isomerized," back into 11 cis retinaldehyde, which completes the visual cycle. Scientists have for two decades been attempting to identify the retinoid isomerase enzyme that catalyzes this regeneration of 11 cis retinaldehyde. Scientists have also been stumped by the function of the Rpe65 protein

Working with Travis at the Jules Stein Eye Institute, Dr. Minghao Jin, visiting assistant researcher in ophthalmology, performed an expression screen in cultured human cells, looking for a gene that caused these cells to convert vitamin A into 11 cis retinol.

The researchers are now studying the effects on retinoid isomerase activity of specific disease causing mutations in the RPE65 gene, which should provide more data on the cause of Leber congenital amaurosis and on how the Rpe65 protein works. The researchers are also examining the function of other proteins that work closely with Rpe65. Mutations in the genes for these interacting proteins are linked to other forms of human blindness.

"These results settle the long standing mystery about the identity of the retinoid isomerase," Travis said. "Scientists have been searching for this enzyme for almost 20 years. Our results also explain why finding this enzyme has been so difficult, until now."

Other researchers on this project besides Travis and Jin are Hui Sun, assistant professor of physiology at UCLA, and Songhua Li and Walid Moghrabi, staff research associates at the Jules Stein Eye Institute.

Enrique Rivero | EurekAlert!
Further information:
http://www.mednet.ucla.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>