01.07.09, 08:00 PM EST
Researchers find it prolongs lives of key vision cells in mice
THURSDAY, Jan. 8 (HealthDay News) -- Researchers working with mice have identified a protein that appears to prolong the lives of retinal cells in both healthy and diseased eyes.
The discovery could one day lead to treatments that would prevent blindness among people genetically predisposed to develop retinal disease, the scientists said.
The protein, known as histone deacetylase 4 (HDAC4), is naturally produced by both mice and humans and is typically involved in the regulation of bone and muscle development.
Reducing the amount of HDAC4 to below-normal levels appears to lead to premature photoreceptor cell death in healthy eyes, the study revealed. In contrast, increasing quantities of this protein to above-normal levels appears to protect the lifespan of these critical vision cells -- both in healthy mouse eyes and in those mice suffering from a genetic flaw, also present in humans, that gives rise to degenerative retinal disease.
The finding -- if replicated in people -- could ultimately lead to new interventions to prevent such disease-driven blindness, or even to the development of methods to restore lost sight to diseased retinas.
"There are some inherited genetic defects that lead to the death of the two types of photoreceptor cells in the eye that capture light, first directly killing the rod cells and then the cone cells which depend on rod cell survival," explained study author Bo Chen, a postdoctoral research fellow with the Howard Hughes Medical Institute at Harvard Medical School in Boston. "So, this mutation eventually leads to complete blindness."
"But what we found," Chen noted, "is that we could actually promote the survival of these genetically affected photoreceptors by introducing more of this particular protein, even though the photoreceptors themselves continue to remain genetically defective."
Chen and his colleagues report their findings in the Jan. 9 issue of Science.
The findings are based solely on a series of neural cell experiments, focused on the retinal health of live mice, that were designed to assess the impact of both under-expression and overexpression of the HDAC4 protein.
Subsequent lab work led the researchers to determine that in sufficient quantities the protein indeed displays a protective effect against eye cell death and thereby has an "essential role in neuronal survival," they wrote.
Yet despite expressing enthusiasm for his current work, Chen emphasized the ongoing nature of the effort.
"Even though the genetics are the same in mice and humans, at this stage it's really very experimental," he stressed. "And much more work needs to be done before we know this will be efficacious in humans."
Nevertheless, Dr. Robert Cykiert, a clinical associate professor of ophthalmology at New York University Langone Medical Center in New York City, described the current work as an "impressive" effort.
"Clearly a lot of people go blind from retinal diseases," he said, noting that glaucoma and macular degeneration are two serious conditions that result from retinal cell death. "And this protein they worked with appears to be what we call neuro-protective, in that it has protective benefits on both the photoreceptor layer that gets damaged in macular degeneration as well as on the ganglion cell layer which is damaged by glaucoma. So this finding could actually turn out to be a major accomplishment, affecting a lot of patients down the road."
However, Rando Allikmets, an associate professor of ophthalmology, pathology and cell biology at Columbia University in New York City, took Chen's cue in cautioning that the true measure of the current work awaits human clinical trials.
"It's a very good study, an interesting observation and a very encouraging finding that will definitely lead to an investigation of this pathway for possible therapeutic targets," he said. "But the problem is that they have identified a protein involved with very basic functions -- including muscle development and bone growth -- so it's very difficult to predict if what they did in mice can be done in humans at all and, even if it can, if it will work in the same way."
Cykiert agreed.
"Of course, it's a mouse study," he acknowledged. "So you certainly don't know if what they've found will be reproduced in patients. And in any case, it would take 10 years to develop any drugs from this that might benefit people. So, yes, it's just a first step."
Friday, January 9, 2009
Saturday, January 3, 2009
In vivo 3D cellular imaging of eyes is aim of extended research grant
DECEMBER 30, 2008--The National Eye Institute (Bethesda, MD) has awarded a $5 million research grant to ophthalmologist John S. Werner of the University of California-Davis and researchers at three other universities. The grant will fund continued development of technology for three-dimensional imaging of cells in the living eye.
The studies, part of the next five-year phase of a Bioengineering Research Partnership, could benefit increasing numbers of patients suffering from glaucoma and age-related macular degeneration. Cell-level imaging of eyes would provide significant advances in understanding the origins of retinal and optic nerve disease and in evaluating novel therapies for a wide spectrum of blinding diseases.
"Our project has been described as the Hubble telescope of the eye," said Werner, the project's principal investigator and a professor at the UC Davis Health System Eye Center.
"Vision and visual disorders begin at the cellular and molecular levels, yet the ability to visualize most cellular structures in vivo continues to elude scientists and clinicians," said Werner, whose research interests include changes in vision across the life span and diseases of the retina and optic nerve. "Despite extraordinary advances in retinal imaging, only a small fraction of human retinal cells have been visualized in the living eye."
The first phase of the partnership, started in 2003, combined adaptive optics and optical coherence tomography (OCT) to provide high-lateral and high-axial resolution, respectively. The initial phase also was funded by a five-year, $5 million grant from the National Eye Institute.
Led by Werner, investigators used this new instrumentation to create volume images of structures previously only visible with histology, including the photoreceptor outer segments, Fibers of Henle, individual optic nerve fiber bundles, detailed structures within the drusen, or lesions, of macular degeneration patients, and the fine structure of the lamina cribosa of the optic nerve. They developed instrumentation with sufficient resolution to image all the major retinal neurons in three dimensions.
However, while the resolution of their instruments reached the cellular scale, many cells and structures of interest were of low contrast. As a result, the major engineering focus of the next five years will be on contrast enhancement through additional imaging techniques. The resulting adaptive optics and optical coherence tomography instruments will permit human in vivo imaging with sufficient resolution and contrast to visualize the smallest of cells in the human retina.
Partner institutions include Duke University, Department of Bioengineering; Indiana University, Department of Optometry; and Lawrence Livermore National Laboratory, Physics and Advanced Technologies Section.
The project's engineering aims have parallel clinical/vision science objectives, including advancing the understanding of changes in cell layers associated with the most common worldwide diseases leading to blindness, including age-related macular degeneration and glaucoma.
More information:
John Werner's Vision Science and Advanced Retinal Imaging lab
The studies, part of the next five-year phase of a Bioengineering Research Partnership, could benefit increasing numbers of patients suffering from glaucoma and age-related macular degeneration. Cell-level imaging of eyes would provide significant advances in understanding the origins of retinal and optic nerve disease and in evaluating novel therapies for a wide spectrum of blinding diseases.
"Our project has been described as the Hubble telescope of the eye," said Werner, the project's principal investigator and a professor at the UC Davis Health System Eye Center.
"Vision and visual disorders begin at the cellular and molecular levels, yet the ability to visualize most cellular structures in vivo continues to elude scientists and clinicians," said Werner, whose research interests include changes in vision across the life span and diseases of the retina and optic nerve. "Despite extraordinary advances in retinal imaging, only a small fraction of human retinal cells have been visualized in the living eye."
The first phase of the partnership, started in 2003, combined adaptive optics and optical coherence tomography (OCT) to provide high-lateral and high-axial resolution, respectively. The initial phase also was funded by a five-year, $5 million grant from the National Eye Institute.
Led by Werner, investigators used this new instrumentation to create volume images of structures previously only visible with histology, including the photoreceptor outer segments, Fibers of Henle, individual optic nerve fiber bundles, detailed structures within the drusen, or lesions, of macular degeneration patients, and the fine structure of the lamina cribosa of the optic nerve. They developed instrumentation with sufficient resolution to image all the major retinal neurons in three dimensions.
However, while the resolution of their instruments reached the cellular scale, many cells and structures of interest were of low contrast. As a result, the major engineering focus of the next five years will be on contrast enhancement through additional imaging techniques. The resulting adaptive optics and optical coherence tomography instruments will permit human in vivo imaging with sufficient resolution and contrast to visualize the smallest of cells in the human retina.
Partner institutions include Duke University, Department of Bioengineering; Indiana University, Department of Optometry; and Lawrence Livermore National Laboratory, Physics and Advanced Technologies Section.
The project's engineering aims have parallel clinical/vision science objectives, including advancing the understanding of changes in cell layers associated with the most common worldwide diseases leading to blindness, including age-related macular degeneration and glaucoma.
More information:
John Werner's Vision Science and Advanced Retinal Imaging lab
Saturday, December 27, 2008
PSivida's eye treatment in trials for macular degeneration
By Mass High Tech staff
PSivida Ltd., an Australian drug company with U.S. headquarters in Watertown, has announced that its Medidur technology, licensed to Alimera Sciences Inc., has begun an early-stage clinical trial for treating macular degeneration. The technology is currently in Phase 3 clinical trials for treating a different disease associated with blindness, diabetic macular edema.
Medidur is a tiny insert, injected during an in-office procedure, which is being studied as a way to deliver a low dose of fluocinolone acetonide, a corticosteroid, to the retina for up to three years as a treatment for DME. To be marketed by Alimera, a privately held ophthalmic pharmaceutical company, the product will go by the name Iluvien if it is approved by the U.S. Food and Drug Administration, pSivida (Nasdaq: PSDV) (ASX: PSD) (FSE: PSI) officials said.
The study is expected to evaluate the effectiveness of Illuvien in treating dry-age related macular degeneration in patients with bilateral geographic atrophy.
In a previous study conducted on animals, Iluvien showed signs of preventing macular degeneration.
Alimera Sciences and pSivida have a worldwide agreement to co-develop and market the Medidur insert for the use of fluocinolone acetonide to treat DME. The agreement also includes the option to identify other compounds for ophthalmic diseases, potentially resulting in three additional products with the Medidur insert.
PSivida Ltd., an Australian drug company with U.S. headquarters in Watertown, has announced that its Medidur technology, licensed to Alimera Sciences Inc., has begun an early-stage clinical trial for treating macular degeneration. The technology is currently in Phase 3 clinical trials for treating a different disease associated with blindness, diabetic macular edema.
Medidur is a tiny insert, injected during an in-office procedure, which is being studied as a way to deliver a low dose of fluocinolone acetonide, a corticosteroid, to the retina for up to three years as a treatment for DME. To be marketed by Alimera, a privately held ophthalmic pharmaceutical company, the product will go by the name Iluvien if it is approved by the U.S. Food and Drug Administration, pSivida (Nasdaq: PSDV) (ASX: PSD) (FSE: PSI) officials said.
The study is expected to evaluate the effectiveness of Illuvien in treating dry-age related macular degeneration in patients with bilateral geographic atrophy.
In a previous study conducted on animals, Iluvien showed signs of preventing macular degeneration.
Alimera Sciences and pSivida have a worldwide agreement to co-develop and market the Medidur insert for the use of fluocinolone acetonide to treat DME. The agreement also includes the option to identify other compounds for ophthalmic diseases, potentially resulting in three additional products with the Medidur insert.
Tuesday, December 16, 2008
PSivida's eye treatment in trials for macular degeneration
By Mass High Tech staff
PSivida Ltd., an Australian drug company with U.S. headquarters in Watertown, has announced that its Medidur technology, licensed to Alimera Sciences Inc., has begun an early-stage clinical trial for treating macular degeneration. The technology is currently in Phase 3 clinical trials for treating a different disease associated with blindness, diabetic macular edema.Medidur is a tiny insert, injected during an in-office procedure, which is being studied as a way to deliver a low dose of fluocinolone acetonide, a corticosteroid, to the retina for up to three years as a treatment for DME. To be marketed by Alimera, a privately held ophthalmic pharmaceutical company, the product will go by the name Iluvien if it is approved by the U.S. Food and Drug Administration, pSivida (Nasdaq: PSDV) (ASX: PSD) (FSE: PSI) officials said.
The study is expected to evaluate the effectiveness of Illuvien in treating dry-age related macular degeneration in patients with bilateral geographic atrophy.
In a previous study conducted on animals, Iluvien showed signs of preventing macular degeneration.
Alimera Sciences and pSivida have a worldwide agreement to co-develop and market the Medidur insert for the use of fluocinolone acetonide to treat DME. The agreement also includes the option to identify other compounds for ophthalmic diseases, potentially resulting in three additional products with the Medidur insert.
Friday, December 12, 2008
Clinical Trial for Macular Degeneration Seeks a New Way of Seeing
The brain's remarkable ability to reorganize itself to compensate for vision loss, the ability called plasticity, may be the key in helping those with age-related macular degeneration (AMD) see better. This theory is the impetus behind a study between Emory Eye Center and the Georgia Institute of Technology (Psychology). Patients who have retinal damage because of AMD sometimes begin to see by using other parts of the intact retina. By "training" these patients to focus on using those good retinal cells, they may experience increased visual acuity.
Susan Primo, OD, MPH, of Emory Eye Center, says the Phase 2 portion of the clinical trial "Age-Related Macular Degeneration and Cortical Reorganization" will help bridge the knowledge gap between cortical plasticity and visual function.
"Results from these studies will begin to provide answers for how behavioral improvements in AMD patients can lead to changes in underlying brain activity and, most importantly, how we can influence those changes to maximize use of remaining vision," Primo says. "Once this link is made, clinicians and healthcare engineers can use the information to design and implement rehabilitation therapies and technologies that will expedite efficient use of fixation strategies ultimately fostering cortical reorganization."
Age-related macular degeneration is the leading cause of blindness in the elderly, accounting for 10 million people who have reduced vision in the United States (Research to Prevent Blindness). AMD is a disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. People in middle-age have about a 2 percent risk of getting AMD, but this risk increases to nearly 30 percent in those over age 75. More than 200,000 develop AMD each year in this country.
"Visual rehabilitation is entering an exciting area of research that expands our current understanding of neuroplasticity of the visual system," says Timothy W. Olsen, director of Emory Eye Center and a retina specialist. "Findings from this study and others may help us understand the tremendous capacity of our central nervous system, especially as it relates to sensory deficits. Combining expertise of the Emory Eye Center with Georgia Tech opens exciting new opportunities in vision research."
Phase 1 of the study appears in the December edition of the journal Restorative Neurology and Neuroscience (Restor Neurol Neurosci. 2008;26(4-5):391-402.)
Phase 1 of the trial at Emory involved seven patients, and the Phase 2 portion at Emory will have 10 patients. The goal will be to study hundreds of patients in the near future. Results will be disseminated in late 2009.
Funding is provided through the Health Systems Institute Seed Grant, a collaboration between Georgia Institute of Technology and Emory University/Children's Healthcare of Atlanta/Egleston. The HSI Seed Grant supports collaborative and interdisciplinary research projects that will help stimulate innovative healthcare research and promote improvements in healthcare. The seed grant awards are specifically designed to provide funding for novel projects that demonstrate a high potential for enhanced diagnostic capabilities of diseases, lead to new inventions that yield new patents, licenses and/or commercial products, lead to high quality peer-reviewed publications and those with high potential to leverage seed funding into extra-mural support.
About Emory Eye Center: The Department of Ophthalmology and Emory Eye Center have a mission to conduct pioneering research into blinding eye diseases, to educate and train eye professionals, and to provide excellent patient care. The Department includes 35 ophthalmologists, seven optometrists, nine basic scientists, 11 post-doctoral fellows, and nine researchers in other Emory departments who hold joint appointments in the Department of Ophthalmology. Ophthalmology research is supported by $6 million in NIH funding. The Department remains in the top rankings (#9 -- 2008) by U.S. News & World Report for the 12 years the magazine has held a ranking for Ophthalmology. It also ranks in the Top Ten in all four categories surveyed by Ophthalmology Times annual report.
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, and health care. Its components include schools of medicine, nursing, and public health; the Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.
Tuesday, December 9, 2008
Study Shows Lutein and Zeaxanthin Protect Against Age-Related Macular Degeneration
by David Gutierrez, staff writer
(NaturalNews) Researchers from Ohio State University may have discovered a mechanism by which proteins known as xanthophylls help prevent against age-related vision loss, they reported in a study published in the Journal of Lipid Research.
"Our research to understand this mechanism might provide a greater appreciation for how one could intervene to possibly slow macular degeneration," said senior study author Earl Harrison.
Age-related macular degeneration is one of the most common causes of age-related vision loss and affects approximately 10 million people in the United States. The deterioration of the macula, a tissue located in the center of the retina, causes vision in the center of the eye to blur, which lead to functional blindness. The condition cannot be reversed once it develops; it can only be slowed.
Prior research has suggested that the xanthophyll proteins lutein and zeaxanthin may protect against the eight-related macular degeneration by filtering out potentially harmful light from the blue end of the spectrum and also protecting the eye against damage from oxidation. The two proteins have been observed to concentrate in the macula, forming a yellow spot.
In the current study, researchers tested the hypothesis that the xanthophylls are transported to the macula by proteins known as scavenger receptor class B, type 1 (SR-B1). They treated pigment cells from the lining of the human retina with lutein, zeaxanthin and the related compounds beta-carotene, finding that the cells absorbed more xanthophylls than they did beta-carotene.
The researchers then blocked the action of SR-B1 by one of two methods. Both of the methods led to a decrease in xanthophyll of distortion of 41 to 87 percent.
Lutein and zeaxanthin cannot be synthesized by the body, but must be consumed in foods such as green, leafy vegetables, peas, summer squash, or yellow and orange fruits and vegetables (including carrots, papaya and peaches).
Sources for this story include: www.sciencedaily.com.
(NaturalNews) Researchers from Ohio State University may have discovered a mechanism by which proteins known as xanthophylls help prevent against age-related vision loss, they reported in a study published in the Journal of Lipid Research.
"Our research to understand this mechanism might provide a greater appreciation for how one could intervene to possibly slow macular degeneration," said senior study author Earl Harrison.
Age-related macular degeneration is one of the most common causes of age-related vision loss and affects approximately 10 million people in the United States. The deterioration of the macula, a tissue located in the center of the retina, causes vision in the center of the eye to blur, which lead to functional blindness. The condition cannot be reversed once it develops; it can only be slowed.
Prior research has suggested that the xanthophyll proteins lutein and zeaxanthin may protect against the eight-related macular degeneration by filtering out potentially harmful light from the blue end of the spectrum and also protecting the eye against damage from oxidation. The two proteins have been observed to concentrate in the macula, forming a yellow spot.
In the current study, researchers tested the hypothesis that the xanthophylls are transported to the macula by proteins known as scavenger receptor class B, type 1 (SR-B1). They treated pigment cells from the lining of the human retina with lutein, zeaxanthin and the related compounds beta-carotene, finding that the cells absorbed more xanthophylls than they did beta-carotene.
The researchers then blocked the action of SR-B1 by one of two methods. Both of the methods led to a decrease in xanthophyll of distortion of 41 to 87 percent.
Lutein and zeaxanthin cannot be synthesized by the body, but must be consumed in foods such as green, leafy vegetables, peas, summer squash, or yellow and orange fruits and vegetables (including carrots, papaya and peaches).
Sources for this story include: www.sciencedaily.com.
Sunday, December 7, 2008
Avastin problems crop up for eye patients
'They’re taking it out of its (original) packaging, repackaging it and injecting it into people’s eyes'
TORONTO — Public health authorities in Canada are investigating a spike in cases of eye inflammation among patients being treated for macular degeneration with the cancer drug Avastin.
First noticed in British Columbia, there appears to be a rise in cases in other parts of the country as well.
And now authorities are trying to draw the potential problem to the attention of the global public health community in the hopes of seeing if it is being observed elsewhere.
The problem is believed to stem from a particular lot of the drug that was distributed widely around the world, though not to the United States. The lot number is B3002B028.
The drug’s manufacturer, the Swiss pharmaceutical firm Roche, is co-operating with Health Canada and the British Columbia Centre for Disease Control, which was alerted to the problem by ophthalmologists.
The situation puts Roche in an awkward position. Avastin is a colon cancer drug; it is not approved for use as a treatment age-related macular degeneration.
And Roche doesn’t want to encourage the off-label use of the drug by ophthalmologists who have embraced it as a much cheaper alternative to a similar drug, Lucentis, which has been approved as a treatment for macular degeneration.
"Absolutely we do not recommend this," said Samantha Ouimet, a spokeswoman for Roche Canada.
"They’re taking it out of its (original) packaging, repackaging it and injecting it into people’s eyes. This comes in a bag and it’s meant for intravenous use for people with cancer."
Ouimet said the company is in discussions with Health Canada. But it is reluctant to put out an advisory warning people not to use the drug as a treatment for age-related macular degeneration when the drug was never approved for this purpose.
Any statement could be seen as promoting the off-label use, Ouimet said.
"Is it a delicate situation? Absolutely."
Ophthamologists in British Columbia started noticing a problem in October.
A small portion — under two per cent — of people treated for age-related macular degeneration with Avastin will develop acute intra-ocular inflammation. But between Oct. 3 and Oct. 27, the rates were much higher.
The BC CDC was called in to help investigate the cluster of cases. And they concluded that the rate of inflammation among patients treated with Avastin from the lot in question was almost 10 times higher than the normal rate. The lot is no longer in use there.
Dr. David Patrick, the centre’s director of epidemiology services, submitted a report on the investigation to ProMED, an electronic reporting system that sends out alerts about outbreaks to a mailing list of public health officials, scientists and other interested parties around the world.
Patrick said the team investigating the issue sent out feelers to ophthamologists in about a half-dozen other Canadian centres and has heard back that others too have noticed an increase in cases of inflammation after use.
The inflammation causes cloudy vision, but appears to clear up over time, he said.
Ouimet said there have been no reports of problems from other countries — and no reports of adverse reactions in cancer patients who received treatments from the same lot.
"We have reviewed all the analytical release data for the lot in question. And all the best parameters were within the limits for use in oncology," she said.
"So we found no deviations in the manufacturing process. All the environmental testing was fully compliant. We’ve revisited the batch. It is safe . . . for its indicated purpose."
Patrick said scientists at the University of British Columbia are studying vials of the drug. But so far they haven’t found anything usual.
"On the initial go-through they haven’t determined a chemical difference between the implicated lot and another one. But there may well be further work with that," he said.
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