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"Hydrogels" Boost Ability of Stem Cells to Restore Eyesight and Heal Brains PDF
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Ophthalmology and Optometry
Tuesday, 19 May 2015

hydrogel syringeUniversity of Toronto scientists and engineers have made a breakthrough in cell transplantation using a gel-like biomaterial that keeps cells alive and helps them integrate better into tissue. In two early lab trials, this has already shown to partially reverse blindness and help the brain recover from stroke.

Led by University of Toronto Professors Molly Shoichet and Derek van der Kooy, together with Professor Cindi Morshead, the team encased stem cells in a "hydrogel" that boosted their healing abilities when transplanted into both the eye and the brain. These findings are part of an ongoing effort to develop new therapies to repair nerve damage caused by a disease or injury.

Conducted through the University of Toronto's Donnelly Centre for Cellular and Biomolecular Research, their research was published in the recent issue of Stem Cell Reports, the official scientific journal of the International Society for Stem Cell Research.

Stem cells hold great therapeutic promise because of their ability to turn into any cell type in the body, including their potential to generate replacement tissues and organs. While scientists are adept at growing stem cells in a lab dish, once these cells are on their own—transplanted into a desired spot in the body—they have trouble thriving. The new environment is complex and poorly understood, and implanted stem cells often die or don't integrate properly into the surrounding tissue.

The researchers also showed that these new cells could help restore function that was lost due to damage or disease. One part of the Stem Cell Reports study involved the team injecting hydrogel-encapsulated photoreceptors, grown from stem cells, into the eyes of blind mice. Photoreceptors are the light sensing cells responsible for vision in the eye. With increased cell survival and integration in the stem cells, they were able to partially restore vision.

"After cell transplantation, our measurements showed that mice with previously no visual function regained approximately 15% of their pupillary response. Their eyes are beginning to detect light and respond appropriately," says Dr. Brian Ballios, an expert in stem cell biology and regenerative medicine for retinal degenerative disease, who led this part of the study.

 
Nerve Cells and Blood Vessels in Eye "Talk" to Prevent Disease PDF
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Ophthalmology and Optometry
Tuesday, 05 May 2015

A new study from scientists at The Scripps Research Institute (TSRI) in the US shows that nerve cells and blood vessels in the eye constantly "talk" to each other to maintain healthy blood flow and prevent disease.

"It turns out these neurons produce a chemical critical for the survival of blood vessels and the survival and function of photoreceptors—the most important cells for maintaining sight," said TSRI Professor Martin Friedlander, senior author of the new study.

The study, published online in The Journal of Clinical Investigation, has implications for treating diseases such as diabetic retinopathy and age-related macular degeneration—the leading causes of vision loss in adults. Since the eye is often a good model for understanding the workings of the brain, the findings also provide clues to major neurological diseases such as Alzheimer's.

According to the researchers, an intermediate layer of the retinal blood vessels seems to activate during periods of low oxygen and acts as a "reserve" of blood vessels in the retina. When blood flow and oxygen levels are low, a transcription factor called hypoxia-inducible factor (HIF) triggers the production of a chemical called VEGF. The VEGF then prompts new blood vessel growth, bringing more oxygen to the area.

Unfortunately, these new blood vessels can leak blood and other fluids and obscure vision. This is the case with age-related macular degeneration, a "wet" version, of which causes vision loss in the center of the eye, and diabetic retinopathy, in which some people with diabetes develop blurry or patchy vision.

In the new study, the team focused on neurons called amacrine cells and horizontal cells, which have a known role in "preprocessing" or adjusting electrical signals transmitted to the brain from the photoreceptors after they have been stimulated by light photons. These cells first caught the researchers' attention because they appear to wrap themselves around the blood vessels (all together called the vasculature) of the intermediate layer.

"We wondered if these neurons were actually altering the way the vasculature forms and behaves," said TSRI Research Associate Peter Westenskow, co-first author of the new paper with TSRI Research Associate Yoshihiko Usui.

To try to find out, in one experiment the researchers "knocked out" the production of VEGF in the amacrine and horizontal cells in mice before they were born. They found that these mice never developed normal blood vessels in the intermediate layer, leading to degeneration of the photoreceptors and severe vision impairment.

This was surprising since previous research had given no clues that these cells were an important source of VEGF.

 
Virtual Reality May Be Effective Tool for Evaluating Balance Control in Glaucoma PDF
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Ophthalmology and Optometry
Thursday, 30 April 2015

Virtual Reality - GlaucomaFalls are the leading cause of injury-related death and morbidity in older adults, especially those with a chronic eye disease such as glaucoma. To investigate this problem, a multidisciplinary group of researchers has become the first to use virtual reality technology to develop a new method for measuring balance control in those with glaucoma. The results of their study, published online by Ophthalmology, the journal of the American Academy of Ophthalmology, demonstrate that virtual reality provides a more realistic testing environment compared to traditional testing methods.

People with glaucoma have a more than three times greater risk of falling than those without the condition. Yet, research to date has shown only a weak correlation between results obtained by visual field testing and risk of falls in glaucoma patients. To address this issue, a group of researchers based at the University of California, San Diego, sought to develop a new, more effective approach using virtual reality goggles.

The team of ophthalmologists, vision scientists and engineers studied 42 patients with open-angle glaucoma and 38 healthy subjects as a control. The subjects wore Oculus Rift stereoscopic goggles that can simulate different settings while standing on a force platform, a device that measures balance and movement. Measurements were recorded by the force platform, including when the goggles simulated movement such as moving through a tunnel or a spinning floor, and when the goggles were not worn or were not providing visual stimulation.

During simulated movement, researchers found that participants made balance adjustments that were an average of 30 to 40 percent more pronounced in glaucoma patients than in healthy subjects, who were able to regain balance more quickly than those with glaucoma. The study authors suspect that the pronounced lack of balance control in the subjects with glaucoma may be related to the loss of retinal ganglion cells caused by the disease, which leads to slower visual processing and impaired motion perception.

The study also found that the degree to which balance was lost was strongly linked to a history of falls, which validated the study's methods and metrics. The researchers hope that future studies using this paradigm will help ophthalmologists better understand the relationship between risk of falls and retinal ganglion cell loss in people with glaucoma.

"Measures from traditional static visual field tests do not mimic the visual conditions that occur day-to-day," explained Felipe A. Medeiros, M.D., senior author and professor of ophthalmology and director of the Visual Performance Laboratory at the University of California, San Diego. "With further refinement of this method, we hope that the approach could one day be used to identify patients at high-risk of falling so that preventative measures can be employed at an earlier stage."

 
New Technique Developed Reduces Halo Effect Caused by Lenses PDF
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Ophthalmology and Optometry
Monday, 20 April 2015

Halo Effect LensesIn a recent study published in Optics Communications, scientists from Bar-Ilan University in Israel have presented a new technique that significantly reduces the halo effect that is generated when using multifocal (contact and intra-ocular) lenses and looking at bright point sources in dark conditions.

Presbyopia is a result of natural aging and stems from a gradual thickening and decrease in elasticity of the lens inside the eye. Corrective lenses used to address presbyopia often lead to a halo effect. This is basically a glow or color light pattern observed when looking at a bright source of light in front of a dark background. It is mostly experienced at night when people see halos around street lamps and car headlights, and it can make driving at night unsafe or even impossible in extreme cases.

Co-author of the paper, Prof. Zeev Zalevsky, head of the Electro-Optics study program of the Faculty of Engineering at Bar-Ilan, explains, "Our solution involves smoothening the surface structure of a contact lens or an intra-ocular lens that has extended depth of focus or multifocal capabilities. The smoothening does not complicate the fabrication complexity of the lens and yet yields the same optical performance in treating presbyopia and assisting people after cataract surgery, but with about one order of magnitude smaller. This allows people that use such lenses to be able to use them also at night."

More and more commercial ophthalmic products incorporate EDOF (extended depth of focus) and multifocal technologies in contact and intra-ocular lenses to solve presbyopia. Until now, such lenses were very problematic when used in dark illumination conditions. The researchers say their proposed concept can resolve the above difficulties and make the existing products even more applicable and useful.

 
Stem Cell Injection Soon To Reverse AMD PDF
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Ophthalmology and Optometry
Friday, 17 April 2015

An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration (AMD), according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that slows the progression of the disease, which is the leading cause of vision loss in people over 65.

"This is the first study to show preservation of vision after a single injection of adult-derived human cells into a rat model with age-related macular degeneration," said Shaomei Wang, MD, PhD, lead author of the study published in the journal STEM CELLS and a research scientist in the Eye Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

The stem cell injection resulted in 130 days of preserved vision in laboratory rats, which roughly equates to 16 years in humans. When animal models with macular degeneration were injected with induced neural progenitor stem cells, which derive from the more commonly known induced pluripotent stem cells, healthy cells began to migrate around the retina and formed a protective layer. This protective layer prevented ongoing degeneration of the vital retinal cells responsible for vision.

Cedars-Sinai researchers in the Induced Pluripotent Stem Cell (iPSC) Core, directed by Dhruv Sareen, PhD, with support from the David and Janet Polak Foundation Stem Cell Core Laboratory, first converted adult human skin cells into powerful induced pluripotent stem cells (iPSC), which can be expanded indefinitely and then made into any cell of the human body. In this study, these induced pluripotent stem cells were then directed toward a neural progenitor cell fate, known as induced neural progenitor stem cells, or iNPCs.

"These induced neural progenitor stem cells are a novel source of adult-derived cells which should have powerful effects on slowing down vision loss associated with macular degeneration," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and contributing author to the study. "Though additional pre-clinical data is needed, our institute is close to a time when we can offer adult stem cells as a promising source for personalized therapies for this and other human diseases."

Next steps include testing the efficacy and safety of the stem cell injection in preclinical animal studies to provide information for applying for an investigational new drug. From there, clinical trials will be designed to test potential benefit in patients with later-stage age-related macular degeneration.

 
Carnival Game Mimics Eye Growth PDF
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Ophthalmology and Optometry
Friday, 10 April 2015

Coin Pusher MachineThe motion of coins in a "Penny Pusher" carnival game is similar to the movement of cells in the eye's lens, as described in a new study published in Investigative Ophthalmology & Visual Science (IOVS). This new insight may help scientists understand how the eye maintains its precise shape -- critical for clear vision -- and how cataracts develop.

"If the size, shape or position of the eye is not carefully regulated, we simply will not see clearly," said author Steven Bassnett, PhD, of Washington University School of Medicine, Department of Ophthalmology and Visual Sciences. "However, the mechanisms that tightly control the growth of the eye remain largely unknown."

The recently published paper, The Penny Pusher: A Cellular Model of Lens Growth, describes how Bassnett's group studied mouse eyes for almost four years to learn more about how the eye's growth is regulated. During that time, they tracked where cells were multiplying on the surface of the eye's lens, the spherical, crystal clear portion of the eye just behind the iris (the colored ring near the eye's surface).

Experiments revealed that cells were primarily multiplying in a narrow line on the lens' surface. As new cells formed, they pushed their neighboring cells towards the lens' equator. Cells already at the equator were then pushed away from the surface and into the center of the lens.

This sequence of cellular motion -- where the addition of new cells push existing cells down into the center of the lens -- is similar to the movement of coins in the Penny Pusher carnival game. In the game, a player adds coins to a moving, elevated platform covered in other coins, causing coins at the far edge to fall onto a lower, larger platform and eventually to where the player can collect them.

"We made a physical model of the lens equator using layers of pennies to simulate the division and migration of the lens cells. Our Penny Pusher model looked very similar to [the carnival game]," said Bassnett.

Not only does the Penny Pusher model offer new insight into the regulation of the eye's shape, it suggests a possible mechanism for the development of cataracts. A cataract happens when the lens goes from crystal clear to cloudy, blurring one's vision.

According to the researchers, if a narrow line of cells on the lens' surface are forming new cells, then those relatively few cells could have a massive effect on the clarity of the lens. "We are currently examining whether mutations in the DNA of individual lens cells can be transmitted to large numbers of lens cells, potentially influencing the clarity of the tissue and resulting in cataract," explained Bassnett.

The researchers involved in this study believe that future success in this area of research could one day be credited to a seemingly unrelated carnival game.

 
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