Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

From Gene Discovery to Preventing Eye Disease

23.03.2005


Retinitis pigmentosa (RP) is an inherited eye disease that causes visual disability leading to blindness. Over the last 15 years, researchers have pinpointed defects in dozens of genes causing different forms of RP. Surprisingly, patients with the same genetic defect can show different severities of vision loss and rates of disease progression. This effect is most dramatic across the retina of some individuals where regions with normal vision can abut regions of no vision. Environmental factors have been near the top of the suspect list for this variation in severity. An environmental factor experienced by all, but to varying extents, is exposure to light – bright lights have been previously speculated to accelerate certain forms of RP.

Now, investigators from the University of Pennsylvania and Cornell University provide evidence for retinal injury caused by moderate light exposure in dogs with a mutation in the rhodopsin gene. Since the blindness in these dogs mimics that observed in human RP caused by mutations in the rhodopsin gene, the investigators strongly recommend limiting excess light exposure in these patients.

“Rhodopsin is the light-catching molecule within rod photoreceptor cells that afford us with night vision,” says Artur V. Cideciyan, PhD, Research Associate Professor of Ophthalmology at Penn’s Scheie Eye Institute, and lead author of the current study published online this week in the Proceedings of the National Academy of Sciences.



“About 100 mutations in the rhodopsin gene have been shown to cause RP but our understanding of the steps between mutant proteins and death of rod photoreceptors remains incomplete,” says Cideciyan. “What we know is that there are at least two ways in which rhodopsin mutations lead to blindness. Some mutations destroy vision in early life and children are left with only impaired day vision, which then disappears. In other mutations, night vision can be present throughout life but has a characteristically slowed recovery time in the dark. Decline of vision is gradual. Naturally occurring rhodopsin mutant dogs that we studied mimic the latter type of human disease.”

Cideciyan and colleagues Samuel G. Jacobson, MD, PhD, the F.M. Kirby Professor in Penn’s Department of Ophthalmology and Director of the Center for Hereditary Retinal Degenerations at Scheie, Gustavo D. Aguirre, VMD, PhD, Professor of Medical Genetics and Ophthalmology at Penn’s School of Veterinary Medicine, and Gregory M. Acland, BVSc, of Cornell University asked whether modest light levels cause damage to retinas of the rhodopsin mutant dogs. The investigators performed the routine clinical procedure of retinal photography in the dogs. Normal dogs had no ill effects of the procedure. Surprisingly, the mutant dogs had complete degeneration one month after retinal photography and only in those regions that were photographed. There were no abnormalities associated with neighboring regions of the retina that were not photographed. Further experiments with focal light exposures and cross-sectional retinal imaging showed that retinal injury was detectable within 30 minutes and could cause complete retinal degeneration within a month following these moderate lights.

“Rhodopsin mutant dogs are one of several naturally occurring canine retinal degenerations which duplicate human hereditary eye diseases,” comment Aguirre and Acland, who have spent more than 20 years identifying and investigating inherited veterinary retinal degenerations and their treatments. “Identifying a light-induced component to the natural history of retinal degeneration in the rhodopsin mutant dogs means that now we can test new treatments for value and safety before attempting the same in human patients.”

When the investigators used lower light exposure levels, the degeneration process was slower and lasted six months or longer. Even further lowering of light exposure resulted in retinal injury that could be repaired over a period of weeks to months.

“It is tempting to speculate that extremely slow recovery of vision following light exposure observed in patients with rhodopsin mutations may represent the human equivalent of retinal repair mechanisms observed in the rhodopsin mutant dogs,” says Cideciyan. “Better understanding of the components of this repair mechanism may lead to new treatment strategies based on augmentation of innate repair.”

“The potentially damaging effects of environmental light have been well-studied and discussed in the past,” adds Jacobson. “Now, we have clues that a specific subgroup of patients may be far more vulnerable to light than others. These patients should be identified clinically and by gene testing and then counseled about this vulnerability. A clinical trial is definitely indicated.”

The research from the Penn-Cornell investigators ushers in a new era of eye-disease prevention by considering the interaction of genetics and environment – in this case exposure to light – on an individual basis. The investigators recommend that all patients with the clinical diagnosis of RP should see an RP specialist to determine their family pattern (the every generation or dominant form is the vulnerable one), their eye disease pattern by specialized (low-light level) testing, and the genetic cause of their RP to know whether this research applies to them and their family members.

Other members of the research team are Tomas Aleman, Alexander Sumaroka, and Danian Gu from Penn, as well as Susan Pearce-Kelling from Cornell. The research was sponsored by the National Eye Institute of the National Institutes of Health, Foundation Fighting Blindness, Macula Vision Research Foundation, F.M. Kirby Foundation, Macular Disease Foundation, Research to Prevent Blindness, Mackall Foundation, ONCE International Prize from Spain, and the Van Sloun Fund.

| EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>