Effectiveness of Chinese Drug for Cataracts Supported by New Tests

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Posted on 30th July 2011 by Pacific ClearVision Institute in Cataracts

Scientists have said that a widely used non-prescription drug in China and certain other countries can prevent and treat cataracts.

In the study, Tzu-Hua Wu, Fu-Yung Huang, Shih-Hsiung Wu and colleagues note that eye drops containing pirenoxine, or PRX, have been reputed as a cataract remedy for almost 60 years.

Currently, the only treatment for cataracts in Western medicine is surgical replacement of the lens, the clear disc-like structure inside the eye that focuses light onto the nerve tissue in the back of the eye.

Despite the wide use of pirenoxine, there have been few scientific studies on its actual effects, the scientists note.

To fill that gap, scientists tested pirenoxine on cloudy solutions that mimic the chemical composition of the eye lens of cataract patients. The solutions contained crystallin – a common lens protein – combined with either calcium or selenite, two minerals whose increased levels appear to play key roles in the development of cataracts. Presence of PRX reduced the cloudiness of the lens solution containing calcium by 38 percent and reduced the cloudiness of the selenite solution by 11 percent.

“These results may provide a rationale for using PRX as an anti-cataract agent and warrant further biological studies,” the article noted.

The study has been published in Inorganic Chemistry, an ACS journal.

Smart Phone Doubles Up as an Eye Specialist to Detect Cataract

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Posted on 30th July 2011 by Pacific ClearVision Institute in Cataracts

The Camera Culture group of the Media Lab at the Massachusetts Institute of Technology (MIT) have developed an innovative software for the smartphone which is capable of detecting cataract.

This whole procedure which hardly takes anytime works with a clip-on device and specially developed software.

“The new device system basically works as radar for the human eye. Just as beam of weather radar sweeps across the sky to detect clouds, it sweeps a beam of light across the eye to detect the cloudy patches called cataracts,” said Ramesh Raskar, head of the Camera Culture group.

Low Vitamin C Levels Linked to Cataract Formation

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Posted on 30th July 2011 by Pacific ClearVision Institute in Cataracts

A new study published in the journal Ophthalmology suggests that low levels of vitamin C can increase the risk of cataracts especially among people living in lower income countries.

The study, conducted by a group of Indian researchers, tested more than 5,600 elderly over 60 years of age for cataracts and also questioned them regarding their diet and the level of vitamin C in their blood.

While over 73 percent of the elderly were found to suffer from cataracts, the researchers found that the number dipped among those who had high levels of vitamin C in their blood.

The researchers found that the risk of cataracts dropped by 39 percent among those who had the highest levels of vitamin C compared to those who had the lowest.

Source-Medindia.net

The Brain’s Connectome — From Branch to Branch

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Posted on 30th July 2011 by Pacific ClearVision Institute in Retina

The human brain is the most complex of all organs, containing billions of neurons with their corresponding projections, all woven together in a highly complex, three-dimensional web. To date, mapping this vast network posed a practically insurmountable challenge to scientists. Now, however, a research team from the Heidelberg-based Max Planck Institute for Medical Research has developed a method for tackling the mammoth task. Using two new computer programs, KNOSSOS and RESCOP, a group of over 70 students mapped a network of more than 100 neurons — and they did so faster and more accurately than with previous methods.

With some 70 billion neurons and hundreds of thousands of kilometres of circuits, the human brain is so complex that, for many years, it seemed impossible to reconstruct the network in detail. Each neuron is linked to about a thousand others by means of finely branched projections called dendrites and axons, and communicates with them using electrical signals. The connections between the cells are critical for brain function, so neuroscientists are keen to understand the structure of these circuits — the connectome — and to reconstruct it in a three-dimensional map. Since no computer is powerful enough yet for the task, researchers are dependent on the human eye. However, the sheer number of cellular connections contained in even the tiniest fragment of tissue makes the undertaking seem pointless — unless it is shared among a large number of people.

Moritz Helmstaedter, Kevin L. Briggman and Winfried Denk, scientists at the Max Planck Institute for Medical Research in Heidelberg, have now successfully tested this procedure. They developed a special software tool called RESCOP which summarises the results of several annotators to yield an overall picture. In this way, and with the support of over 70 students from Heidelberg University, they reconstructed a network of over 100 neurons from the retina in full detail.

The students used the KNOSSOS software developed by the team in Heidelberg to trace the connections between the neurons. It is no coincidence that the program is named after Crete’s legendary palace, renowned for its elaborate labyrinth: “Tracing the connections in the brain is at least as hard as finding your way out of a mythological labyrinth,” explains Moritz Helmstaedter.

In order to reconstruct a neural circuit, researchers start by staining the neurons of a section of tissue with heavy metals to make them visible. Using three-dimensional electron microscope images, they start at the cell body and follow the dendrites and axons, marking the branch point nodes on the screen. Then they use the computer to generate a three-dimensional image of the section. In this way, they work their way through the tangle of neurons bit by bit. It is a tedious undertaking: One person working alone with the currently available programs would take at least 30 years to reconstruct a path of 30 centimetres in length. Besides, these procedures are prone to error, since the branch points are not always easily recognised and the annotator’s attentiveness decreases with time.

The KNOSSOS software considerably reduces the time required: It is about 50 times faster than other programs used up to now. In addition, the RESCOP program now makes it possible for dozens of people to work on the reconstruction at the same time. Since the method is easily learned, even non-experts can use it. Most of the students worked from home and sent their results to the scientists via e-mail. The scientists were able to establish that the error rate of the best students was no higher than that of experienced neurobiologists. Moreover, its sophisticated algorithms enable RESCOP to detect and average out inaccuracies. This means that the reconstruction is not only faster, but also more reliable than before.

“For the first time ever, these new programs could make it possible for us to unravel the complicated neural network of the brain — a task far more complex than decoding the human genome,” says Winfried Denk. Next, the scientists plan to reconstruct a fragment of the mouse cerebral cortex, as this is where all the important mental processes occur.

Researchers Invent New Drug Delivery Device to Treat Diabetes-Related Vision Loss

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Posted on 30th July 2011 by Pacific ClearVision Institute in Retina

A team of engineers and scientists at the University of British Columbia has developed a device that can be implanted behind the eye for controlled and on-demand release of drugs to treat retinal damage caused by diabetes.

Diabetic retinopathy is the leading cause of vision loss among patients with diabetes. The disease is caused by the unwanted growth of capillary cells in the retina, which in its advanced stages can result in blindness.

The novel drug delivery mechanism is detailed in the current issue of Lab on a Chip, a multidisciplinary journal on innovative microfluidic and nanofluidic technologies.

The lead authors are recent PhD mechanical engineering graduate Fatemeh Nazly Pirmoradi, who completed the study for her doctoral thesis, and Mechanical Engineering Assoc. Prof. Mu Chiao, who studies nanoscience and microelectromechanical systems for biological applications.

The co-authors are Prof. Helen Burt and research scientist John Jackson at the Faculty of Pharmaceutical Sciences.

“We wanted to come up with a safe and effective way to help diabetic patients safeguard their sight,” says Chiao who has a family member dealing with diabetic retinopathy.

A current treatment for diabetic retinopathy is laser therapy, which has side effects, among them laser burns or the loss of peripheral or night vision. Anti-cancer drugs may also used to treat the disease. However, these compounds clear quickly from the bloodstream so high dosages are required, thus exposing other tissues to toxicity.

Key to UBC’s innovation is the ability to trigger the drug delivery system through an external magnetic field. The team accomplished this by sealing the reservoir of the implantable device — which is no larger than the head of a pin — with an elastic magnetic polydimethylsiloxane (silicone) membrane. A magnetic field causes the membrane to deform and discharge a specific amount of the drug, much like squeezing water out of a flexible bottle.

In a series of lab tests, the UBC researchers loaded the implantable device with the drug docetaxel and triggered the drug release at a dosage suitable for treating diabetic retinopathy. They found that the implantable device kept its integrity with negligible leakage over 35 days.

They also monitored the drug’s biological effectiveness over a given period, testing it against two types of cultured cancer cells, including those found in the prostate. They found that they were able to achieve reliable release rates.

“The docetaxel retained its pharmacological efficacy for more than two months in the device and was able to kill off the cancer cells,” says Pirmoradi.

The UBC device offers improvements upon existing implantable devices for drug delivery, says Chiao.

“Technologies available now are either battery operated and are too large for treating the eye, or they rely on diffusion, which means drug release rates cannot be stopped once the device is implanted — a problem when patients’ conditions change.”

Pirmoradi says it will be several years before the UBC device is ready for patient use. “There’s a lot of work ahead of us in terms of biocompatibility and performance optimization.”

The team is also working to pinpoint all the possible medical applications for their device so that they can tailor the mechanical design to particular diseases.

Next Generation Gene Therapy

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Posted on 30th July 2011 by Pacific ClearVision Institute in Retina

Inspired by earlier successes using gene therapy to correct an inherited type of blindness, investigators from the Perelman School of Medicine at the University of Pennsylvania, are poised to extend their approach to other types of blinding disorders.

In a previous human trial conducted at the Children’s Hospital of Philadelphia and Penn, researchers packaged a normal version of a gene missing in Leber’s congenital amaurosis (LCA) inside a genetically engineered vector, called an adeno-associated virus (AAV). The vector delivered the gene to cells in the retina, where the gene produces an enzyme that restores light receptors.

“The results from three Phase I clinical trials for LCA showed the potential for gene therapy based on adeno-associated viruses delivering corrective genes to the retina,” notes co-senior author Jean Bennett, MD, PhD, the F.M. Kirby professor of Ophthalmology. “To broaden treating inherited eye diseases, we will need a larger vector toolkit, and what we have seen of AAV8 gives us hope for creating gene therapies for diseases that attack the retina’s photoreceptors. This preclinical study provides the guidance we need to formulate dose level and type of vector to deliver corrective genes to treat blindness caused by the loss of photoreceptors.”

In the present study, published in Science Translational Medicine this week, the Penn team compared the safety and efficiency of delivery in an animal model of two different types of AAVs — AAV2, which was used in the human trials for LCA, and AAV8, a second-generation AAV technology initially discovered in the lab of co-senior author James M. Wilson, MD, PhD, professor of Pathology and Laboratory Medicine.

The researchers used both vectors to deliver a green fluorescent protein (GFP) transgene to the retinal pigment epithelial (RPE) cells and photoreceptor cells of nonhuman primates. Photoreceptor cells are the problem area for other retinal diseases such as retinitis pigmentosa (RP) and others, for which there is no treatment. Photoreceptors are specialized nerve cells that convert light into a biological electrical signal and are designated as rods and cones.

“We showed that we can use AAV8 to deliver genes to the photoreceptor of the primate eye at lower doses, both safely and efficiently,” says first author Luk H. Vandenberghe, PhD, Senior Investigator, Gene Therapy Program, and currently at Penn’s F.M. Kirby Center for Molecular Ophthalmology.

Both AAV2 and AAV8 delivered the gene safely and efficiently to the monkey retinas, but AAV8 was markedly better at targeting photoreceptor cells.

The STM study describes the dose relationship between AAV2 and AAV8 vectors and their target cells and the immune response in the nonhuman primate retina. From this the researchers found dosage thresholds to safely and efficiently target cells in the outer retina such as RPE cells and rod and cone photoreceptors. While AAV2 and AAV8 efficiently delivered the gene to RPE cells at moderate to low doses, expression of the GFP gene in rod and cone photoreceptors was reached only at higher dosages. Substantial delivery to rods was obtained with moderate doses of AAV8, doses similar to those currently used in experimental clinical protocols.

The vectors at intermediate doses did not cause problematic immune responses and post-surgical injection complications. The delivered gene also stayed in the retina at very high levels throughout the study duration of four months. Additionally, the GFP gene was preferentially transduced to one type of retinal ganglion cells, which surprised the researchers. In general retinal ganglion cells transmit visual information from the retina to several regions of the brain. This knowledge could be used in the future to further delineate the neuronal connections between the retina and the brain.

In earlier animal studies, AAV8 also delivered genes safely and efficiently to the mouse retina. However, the mouse retina differs significantly from the primate retina, most notably in structure, which affects the surgical approach to delivering corrective genes to different parts of the eye. (For example, mice do not have a macula — the eye structure used for visual discrimination, which is affected in macular degeneration — and primates do.) The present study in nonhuman primates is the next step to better translate treatment strategies for people.

“To address patients with other retinal diseases, we need a renaissance of technology–new and better vectors to safely and effectively deliver corrective genes to a range of diseases,” says Wilson. “My lab has recently isolated new families of simian-based adenoviruses and adeno-associated viruses. Recombinant versions of these viruses are turning out to be useful as improved gene transfer vehicles to a variety of targets.”

The other co-authors, all from Penn, are Peter Bell, Albert M. Maguire, Cassia Cearley, Ru Xiao, Roberto Calcedo Lili Wang, Michael J. Castle, Alexandra C. Maguire, Rebecca Grant, and John H. Wolfe. Maguire, Bennett, and Wolfe also have affiliations with The Children’s Hospital of Philadelphia.

The study was supported by grants from GlaxoSmithKline Pharmaceuticals Inc.; Foundation Fighting Blindness, Research to Prevent Blindness; the Paul and Evanina Mackall Foundation Trust; the F. M. Kirby Foundation; the National Institute of Neurological Disorders and Stroke; the National Center for Research Resources; and the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania.

Study Evaluates Eye Findings After Use of Intra-Arterial Chemotherapy for Retinoblastoma

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Posted on 30th July 2011 by Pacific ClearVision Institute in Retina

In a study examining eight eyes that were removed following intra-arterial chemotherapy (IAC) for treatment of retinoblastoma (a tumor of the retina of the eye), there was variable response of the tumor to therapy but also evidence of ocular complications, according to a report published Online First by Archives of Ophthalmology, one of the JAMA/Archives journals.

According to background information in the article, a new but somewhat controversial treatment for retinoblastoma (Rb) is IAC. In this type of therapy, chemotherapy is delivered directly to the eye and the surrounding area by administering the medication through the ophthalmic artery. “The main goal of this approach is to provide sufficient chemotherapy to eradicate the Rb and avoid the toxicities of systemic chemotherapy,” explain the authors.

Ralph C. Eagle, Jr., M.D., from the Wills Eye Institute, Philadelphia, and colleagues examined eight eyes that had been treated with IAC but were later removed (enucleated). The enucleations were performed because the tumors were not responsive to therapy, or because other medical problems, such as a certain type of glaucoma, developed. An ophthalmic pathologist dissected and studied the eyes.

This examination demonstrated that the response to treatment ranged from minimal (one eye), to moderate (one eye), to extensive (four eyes) to complete regression (two eyes). However, a majority of the eyes also showed evidence of complications, including ischemia and atrophy of the retina, blood clots in blood vessels and foreign material within those clots.

“In summary, histopathology of eyes with Rb following IAC showed evidence of complete tumor regression in eyes in which there was clinical tumor regression and also confirmed viable tumor in those in which tumor was suspected clinically,” report the authors. However, the authors also emphasize the importance of the discovery of blood vessel blockages and foreign material in the clots within those vessels. The researchers conclude, “We suggest that IAC for Rb be used with caution.”

Scientists Discover New Role for Vitamin C in the Eye and the Brain

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Posted on 30th July 2011 by Pacific ClearVision Institute in Retina

Scientists Discover New Role for Vitamin C in the Eye and the Brain

Nerve cells in the eye require vitamin C in order to function properly — a surprising discovery that may mean vitamin C is required elsewhere in the brain for its proper functioning, according to a study by scientists at Oregon Health & Science University recently published in the Journal of Neuroscience.

“We found that cells in the retina need to be ‘bathed’ in relatively high doses of vitamin C, inside and out, to function properly,” said Henrique von Gersdorff, Ph.D., a senior scientist at OHSU’s Vollum Institute and a co-author of the study. “Because the retina is part of the central nervous system, this suggests there’s likely an important role for vitamin C throughout our brains, to a degree we had not realized before.”

The brain has special receptors, called GABA-type receptors, that help modulate the rapid communication between cells in the brain. GABA receptors in the brain act as an inhibitory “brake” on excitatory neurons in the brain. The OHSU researchers found that these GABA-type receptors in the retinal cells stopped functioning properly when vitamin C was removed.

Because retinal cells are a kind of very accessible brain cell, it’s likely that GABA receptors elsewhere in the brain also require vitamin C to function properly, von Gersdorff said. And because vitamin C is a major natural antioxidant, it may be that it essentially ‘preserves’ the receptors and cells from premature breakdown, von Gersdorff said.

The function of vitamin C in the brain is not well understood. In fact, when the human body is deprived of vitamin C, the vitamin stays in the brain longer than anyplace else in the body. “Perhaps the brain is the last place you want to lose vitamin C,” von Gersdorff said. The findings also may offer a clue as to why scurvy — which results from a severe lack of vitamin C — acts the way it does, von Gersdorff said. One of the common symptoms of scurvy is depression, and that may come from the lack of vitamin C in the brain.

The findings could have implications for other diseases, like glaucoma and epilepsy. Both conditions are caused by the dysfunction of nerve cells in the retina and brain that become over excited in part because GABA receptors may not be functioning properly.

“For example, maybe a vitamin C-rich diet could be neuroprotective for the retina — for people who are especially prone to glaucoma,” von Gersdorff said. “This is speculative and there is much to learn. But this research provides some important insights and will lead to the generation of new hypotheses and potential treatment strategies.”

Scientists and students in von Gerdorff’s lab in OHSU’s Vollum Institute are dedicated to basic neuroscience research. The vitamin C research work was done using goldfish retinas, which have the same overall biological structure as human retinas.

The retina research work was done by Ph.D. student Evan Vickers, working as part of the von Gersdorff lab. The work was in collaboration with Cecilia Calero in the lab of Dr. Daniel J. Calvo from the University of Buenos Aires, Argentina, and Gustavo Cid and Luis Aguayo from the University of Concepcion, Chile.

The work was funded by the Consejo Nacional de Investigaciones Científicas y Tecnicas (Argentina), the Pew Foundation, the International Brain Research Organization and the National Eye Institute of the National Institutes of Health.

The study was published online in the June 29 issue of the Journal of Neuroscience, which is the official journal of the Society for Neuroscience.