ORNL image analysis prowess advances retina research

Armed with a new ability to find retinal anomalies at the cellular level, neurobiologists at St. Jude Children's Research Hospital have made a discovery they hope will ultimately lead to a treatment for cancer of the retina.

 

While much work remains, Oak Ridge National Laboratory's specialized tracing algorithm allows researchers to analyze thousands of cells instead of just a few dozen. This tool has helped reveal a previously undiscovered role of Rb, the retinoblastoma tumor suppressor gene in the developing retina. The findings are detailed in a paper published in the Proceedings of the National Academy of Sciences, available at http://www.pnas.org/content/early/2011/12/08/1108141108.abstract.

"Our paper shows that horizontal neurons known to be deficient in this gene exhibited abnormalities in the way their dendrites – the arms that connect to other cells – were organized after a certain number of days after birth," said the Department of Energy lab's Ryan Kerekes, one of the authors. The images of mouse retinas were acquired using confocal microscopy while The Jackson Laboratory provided the mice. 

To make their discovery, Kerekes, ORNL colleague Shaun Gleason and postdoc Mahmut Karakaya developed a computer program and automated tool that traces the very complex and intricate dendritic arbor. This tool allows scientists to draw a line along each branch in the neuron's tree of connectors so the branch can be measured in terms of length, angle and other parameters.

"Previously, this was a very time-consuming and labor-intensive process," Kerekes said. "Existing commercial software tools were not tuned to this particular data and, as a result, produced too many tracing errors."

As a result, only a handful of cells could be analyzed in sufficient detail, according to Kerekes, who noted that the ORNL tracing algorithms achieves the level of accuracy required to analyze thousands of developing neurons.

Retinoblastoma is caused by a mutation in a gene controlling cell division, causing cells to grow out of control and become cancerous. It is most commonly found in children 2 and younger.

While this paper focused on cancer of the retina, Gleason noted that this research focuses on a number of retinal developmental issues.

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Israeli company to provide advanced bionic vision to the blind

An Israeli company will provide an advanced bionic vision device to help millions of blind people see the world.

Herzilya-based Nano Retina is developing a prototype medical device, that "if all goes well" could be an answer to the prayers of people worldwide who suffer from impaired eyesight and blindness due to age-related macular degeneration (AMD), diabetes, retinopathy, retinitis pigmentosa, and related illnesses.

The start-up, founded in 2009, aims to make a science-fiction staple, bionic vision, a la Geordi La Forge in Star Trek, a reality within the next few years.

But they want to go further by building a simpler, smaller, lighter and less invasive device.

The heart of the system is a wi-fi - powered chip about the size of a child's fingernail that is attached over the damaged retina within the eyeball. The 30-minute operation would be a relatively simple surgical procedure, similar to a cataract procedure, in which a five millimeter incision is made in the sclera, and the device slid inside and glued to the retina, according to the company.

The potential market for the device and the number of people it could help will simply be immense.

According to the World Health Organization, as of 2010, 285 million (65 percent of whom are aged over 50 years) suffer some degree of visual impairment, and 39 million are estimated to be blind (82 percent over 50). The top three causes are cataracts, glaucoma and age-related macular degeneration.

The device, which the firm calls Bio-Retina, is powered via a small battery mounted in a normal-looking pair of eyeglasses that broadcasts an under-one-milliwatt WiFi signal.

Ra'anan Gefen, Nano-Retina's managing director, told Xinhua on Monday that the "electronic radiation at that level is equivalent to sunlight," and poses no risk to the user.

Bio-Retina then uses the power to operate like a digital camera 's image recording chip: light naturally entering through the pupil falls on the chip, which then sends a 24x24 black and white pixel image via a series of nano-scale electrodes enmeshed within the optic nerve to the brain.

The company believes that full-sight, within the equipment's range, would begin immediately.

Later versions are aiming for 72x72 resolution, according to the firm, with enough resolution to read a large-font book, watch television or engage in similar activities -- essentially giving the blind and near blind back their vision.

While there are close to a dozen groups around the world attempting to come up with similar devices, and with varying degrees of success, Gefen said that the uniqueness of their idea is the number of pixels crowded on the sensor, and the way it's glued within the eyeball, as opposed to sutures, wires and heavier battery packs that other designs use.

"We are working in this incredible, ultra low-power arena, and ours is better than the next best by a factor of ten," Gefen said with pride, adding that "One competitors' model is something like ten volts "that's something like a car battery."

The firm has already demonstrated proof of concept, and Gefen said "we're working on a prototype to show the image end-to-end," and hope to start clinical trials on humans by 2013.

"We're trying to return to the blind a greater sense of independence; to be able to identify the person in front of you visually. The difference is being able to distinguish images, instead of just light and dark," Gefen told Xinhua.

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Mimetogen Pharmaceuticals Announces Initiation of Phase II Clinical Trial of Novel NGF Mimetic in Patients with Dry Eye

Mimetogen Pharmaceuticals Inc., a clinical-stage biotechnology company focused on developing novel small molecule compounds that mimic the effects of neurotrophins,  announced that it has initiated the first human clinical trial evaluating MIM-D3, a mimetic of nerve growth factor (NGF), in a Phase II clinical trial in patients with moderate to severe dry eye disease. MIM-D3 is a small cyclic peptidomimetic of NGF, a naturally occurring protein in the eye that is responsible for the maintenance of corneal nerves and epithelium, mucin and tear production.

The Dry Eye Remedy: The Complete Guide to Restoring the Health and Beauty of Your Eyes

"This is a key development milestone for Mimetogen, as this trial represents the first use of small molecule mimetics of neurotrophins to treat an ocular disease. Encouraging data in animal models of dry eye suggests that the use of neurotrophin mimetics to treat dry eye and other degenerative ocular indications such as glaucoma is an important new approach to treat ocular diseases for which there are currently very limited treatment options, said Garth Cumberlidge, Ph.D., Chief Executive Officer of Mimetogen. "We are excited to have initiated this study, and anticipate receiving data in mid-2011.”

This 150 patient randomized, double-masked, multi-center, placebo-controlled study is designed to evaluate the safety, tolerability and efficacy of MIM-D3 in improving the signs and symptoms of dry eye.

About Dry Eye Disease

Dry eye disease is one of the most common problems treated by ophthalmologists; an estimated 25-30 million Americans suffer from dry eye and the worldwide prevalence closely parallels that of the United States. Dry eye is a chronic multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface.

About Mimetogen Pharmaceuticals

Mimetogen Pharmaceuticals, Inc. began operations in 2006, developing the use of peptidomimetics as novel approaches to treat diseases with high unmet medical needs. The underlying technology has been developed at McGill University and the Lady Davis Institute for Medical Research in Montréal. The Company is currently developing novel therapeutic approaches for ophthalmic indications including dry eye disease, glaucoma and other degenerative diseases of the retina. Mimetogen also possesses a pipeline of lead compounds for non-ophthalmic indications (such as neurodegenerative disease and pain).

Source: Mimetogen Pharmaceuticals Inc

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Enzo Biochem Initiates Clinical Trial for Treatment of Uveitis at NIH

Enzo Biochem, Inc. announced that, following filing of a investigational new drug (IND) application with the FDA, its Enzo Therapeutics division is commencing a clinical trial of Optiquel(TM) , the Company's proprietary oral therapeutic for chronic non-infectious uveitis. The trial is designed as a randomized, double-masked, placebo-controlled study with a long-term follow-up and is being conducted by the National Institute of Health's National Eye Institute (NEI). Robert Nussenblatt, MD, Chief of NEI's Laboratory of Immunology, will serve as Principal Investigator.

Optiquel(TM) has been awarded orphan drug status in the European Union and a similar designation may be applied for in the US. Enzo owns the exclusive rights to both US and international patents claiming the use of this compound for the treatment of uveitis. An investigator-initiated clinical trial of Optiquel(TM) in Germany demonstrated a therapeutic effect with no treatment-related side effects.

Uveitis: Fundamentals and Clinical Practice: Expert Consult - Online and Print

Uveitis is a collective term for a variety of ophthalmic conditions that result in chronic inflammation of the eye involving the uvea, which lies between the outermost and innermost layers of the eye. Uveitis occurs most frequently in relatively young people, ages 20 to 50. A recent study estimated that more than 280,000 people in the United States are affected by uveitis each year, and that the disease is associated with 30,000 cases of blindness annually. It has been estimated that 10-22% of new cases of blindness in the United States result from this disease.

Patients with chronic autoimmune uveitis often require immunosuppressive treatment for an extended period of time. Furthermore, immunosuppressive therapy is frequently associated with side effects, including glaucoma and cataracts that limit the duration and intensity of treatment. 

Optiquel(TM), by contrast, has been designed as a novel and specific immune modulator that utilizes a highly specific down-regulation of the uveitis autoimmune response by oral treatment with an antigen that is very nearly identical to the offending antigen. This tolerogenic approach with Optiquel(TM) is based on Enzo's proprietary oral immune regulation platform, a platform that has been studied extensively across a number of clinical indications. 

"We are pleased to announce the initiation of this clinical trial, and that it will be performed at the National Eye Institute," said Elazar Rabbani, Ph.D., Chairman and CEO of Enzo Biochem. "Chronic non-infectious uveitis is currently treated with steroids and other general immune suppressive therapy, often producing serious and damaging side effects. Optiquel(TM), if it meets its endpoints of reducing the need for high doses of steroid treatment in order to reduce symptoms and improve visual acuity, would represent a significant step forward in the treatment of this affliction." 

Source:  Enzo Biochem, Inc.

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