New Technique to Give Us Better Understanding of Human Tissues

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Posted on 28th June 2012 by Pacific ClearVision Institute in General |Retina

Research from North Carolina State University demonstrates that a relatively new microscopy technique can be used to improve our understanding of human tissues and other biomedical materials. The study focused specifically on eye tissues, which are damaged by scarring in diabetic patients.

“Our findings are a proof of concept, showing that this technique is extremely effective at giving us the data we need on these tissues,” says Dr. Albena Ivanisevic, co-author of a paper describing the research. “Specifically, it gives a great deal of information on the composition of these tissues, as well as the tissue’s topography, or surface characteristics.” Ivanisevic is an associate professor of materials science and engineering at NC State and associate professor of the joint biomedical engineering program at NC State and the University of North Carolina at Chapel Hill.

The study is one of the first to explore how this technology, called bimodal dual AC mode microscopy, can improve our understanding of human tissues and biomaterials.

The research team, which included researchers from Purdue University and the University of Louisville School of Medicine, examined two types of eye tissue from diabetic patients. Specifically, they looked at the inner limiting membrane (ILM), which is the surface layer of the retina, and so-called epiretinal membranes. Epiretinal membranes are scar tissues that form on the ILM in diabetics. Scar tissue can cause significant damage to the retina and, if untreated, may lead to blindness.

There are multiple treatments for this scarring. In the United States, a common technique is for a surgeon to peel off the ILM, removing the scar tissue with it. In many other parts of the world, surgeons inject dye into the eye to better distinguish the parts of the eye they will operate on. This process is not currently allowed in the United States, due to concerns about the dye’s toxicity.

The researchers launched this project, in part, to determine if bimodal dual AC mode microscopy could be used to provide a better understanding of the topographical properties of the ILM. Further, the researchers wanted to use the technology to see if it offered insight into how — or whether — various dyes affect the topographical characteristics of the ILM. “All of this information could be used to improve surgical outcomes and to foster research into additional treatments for the condition,” Ivanisevic says.

The researchers found that bimodal dual AC mode microscopy, an atomic force imaging technique, captured the properties of the tissue in exceptional detail. Atomic force imaging effectively runs a probe over the surface of a material to collect data on its topography, similar to the way in which a record player’s needle runs over the surface of an album.

“The next step would be to use this technology to assess the utility — and potential risk — of various dyes,” Ivanisevic says. “If we can find a dye that is extremely effective and poses little risk, it may be approved for use in future surgeries.”

New Molecules Important for Vision and Brain Function Identified

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Posted on 28th June 2012 by Pacific ClearVision Institute in General

In a pair of related studies, scientists from the Florida campus of The Scripps Research Institute have identified several proteins that help regulate cells’ response to light — and the development of night blindness, a rare disease that abolishes the ability to see in dim light.

In the new studies, published recently in the journals Proceedings of the National Academy of Sciences (PNAS) and The Journal of Cell Biology, Scripps Florida scientists were able to show that a family of proteins known as Regulator of G protein Signaling (RGS) proteins plays an essential role in vision in a dim-light environment.

“We were looking at the fundamental mechanisms that shape our light sensation,” said Kirill Martemyanov, a Scripps Research associate professor who led the studies. “In the process, we discovered a pair of molecules that are indispensible for our vision and possibly play critical roles in the brain.”

In the PNAS study, Martemyanov and his colleagues identified a pair of regulator proteins known as RGS7 and RGS11 that are present specifically in the main relay neurons of the retina called the ON-bipolar cells. “The ON-bipolar cells provide an essential link between the retinal light detectors — photoreceptors and the neurons that send visual information to the brain,” explained Martemyanov. “Stimulation with light excites these neurons by opening the channel that is normally kept shut by the G proteins in the dark. RGS7 and RGS11 facilitate the G protein inactivation, thus promoting the opening of the channel and allowing the ON-bipolar cells to transmit the light signal. It really takes a combined effort of two RGS proteins to help the light overcome the barrier for propagating the excitation that makes our dim vision possible.”

In the Journal of Cell Biology study, Martemyanov and his colleagues unraveled another key aspect of the RGS7/RGS11 regulatory response — they identified a previously unknown pair of orphan G protein-coupled receptors (GPCRs) that interact with these RGS proteins and dictate their biological function.

GPCRs are a large family of more than 700 proteins, which sit in the cell membrane and sense various molecules outside the cell, including odors, hormones, neurotransmitters, and light. After binding these molecules, GPCRs trigger the appropriate response inside the cell. However, for many GPCRs the activating molecules have not yet been identified and these are called “orphan” receptors.

The Martemyanov group has found that two orphan GPCRs — GPR158 and GPR179 — recruit RGS proteins and thus help serve as brakes for the conventional GPCR signaling rather than play an active signaling role.

In the case of retinal ON-bipolar cells, GPR179 is required for the correct localization of RGS7 and RGS11. Their mistargeting in animal models lacking GPR179 or human patients with mutations in the GPR179 gene may account for their night blindness, according to the new study. Intriguingly, in the brain GPR158 appears to play a similar role in localizing RGS proteins, but instead of contributing to vision, it helps RGS proteins regulate the m-opioid receptor, a GPCRs that mediates pleasurable and pain-killing effects of opioids.

“We are really in the very beginning of unraveling this new biology and understanding the role of discovered orphan GPR158/179 in regulation of neurotransmitter signaling in the brain and retina,” Martemyanov said. “The hope is that better understanding of these new molecules will lead to the design of better treatments for addictive disorders, pain, and blindness.”

Fatty Acid Found in Fish Prevents Age-Related Vision Loss, Study Suggests

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Posted on 28th June 2012 by Pacific ClearVision Institute in General |Retina

An omega-3 fatty acid found in fish, known as DHA, prevented age-related vision loss in lab tests, according to recent medical research from the University of Alberta.

Yves Sauvé, a researcher in the Faculty of Medicine & Dentistry, and his team discovered that lab models fed DHA did not accumulate a toxic molecule at the back of the eyes. The toxin normally builds up in the retina with age and causes vision loss.

“This discovery could result in a very broad therapeutic use,” says Sauvé, whose work was recently published in the peer-reviewed journal Investigative Ophthalmology & Visual Science.

“In normal aging, this toxin increases twofold as we age. But in lab tests, there was no increase in this toxin whatsoever. This has never been demonstrated before — that supplementing the diet with DHA could make this kind of difference.”

The team recently started another study, looking at people who have age-related macular degeneration, a condition that results in loss of central vision and is the main cause of blindness in people over the age of 50. The researchers will look for DNA markers in the blood of study participants. The team wants to determine whether participants with certain genetic markers will respond better to increasing amounts of DHA in their diet, and if so, why.

Sauvé is a researcher in the departments of ophthalmology and physiology at the U of A.

Various organizations funded the research; the primary funder was the Canadian Institutes of Health Research.

Antioxidant Shown to Reduce Blindness Risk in Extremely Premature Babies

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Posted on 28th June 2012 by Pacific ClearVision Institute in General |Retina

Retinopathy of prematurity (ROP) is the second most common cause of childhood blindness in the United States, occurring in half of premature infants born earlier than or at 28 weeks gestational age. The condition is caused by abnormal blood vessel development in the retina of the eye. ROP risk increases with decreasing gestational age.

A study by researchers at Brigham and Women’s Hospital (BWH) suggests that the antioxidant, rhSOD (recombinant human Cu/Zn superoxide dismutase), reduces the risk of developing ROP in extremely low gestational age newborns.

The post-hoc analysis study is published online on June 15, 2012 in Neonatology.

Researchers looked at a subset of data from a previous multicenter trial that randomized 302 preterm infants to receive either rhSOD or placebo for prevention of bronchopulmonary dysplasia (a chronic lung condition that affects newborn babies). Researchers analyzed the data looking specifically at the incidence and severity of ROP in extremely low gestational age newborns.

Within the entire cohort, there were no significant differences in ROP in newborns given placebo versus those given rhSOD. However, those born earlier than 26 weeks (72 babies) had a 22 percent reduction in ROP. The abnormality was reduced by 53 percent for babies born earlier than 25 weeks (24 babies).

“Even though strides have been made in developing interventions to stop ROP from progressing to blindness, there are currently no therapies available for ROP prevention,” said Richard Parad, MD, BWH Department of Newborn Medicine, lead study author. “There is a large need for the preventive approach that rhSOD could potentially provide.”

The researchers note that while looking at ROP was not the primary outcome for which the prior study was designed, this post-hoc analysis was carefully re-focused on the tiniest babies with the highest ROP risk based on recent advances in the understanding of how ROP develops and on evidence from prior studies of other antioxidants that suggested such agents might interfere with development of ROP.

In light of the findings, the researchers stress that further studies are required to confirm their observations.

This research was supported by Biotechnology General Corporation (now Savient Pharmaceuticals). rhSOD is currently owned by Ferring Pharmaceuticals.

Scientists See New Hope for Restoring Vision With Stem Cell Help

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Posted on 28th June 2012 by Pacific ClearVision Institute in General |Retina

Human-derived stem cells can spontaneously form the tissue that develops into the part of the eye that allows us to see, according to a study published by Cell Press in the 5th anniversary issue of the journal Cell Stem Cell. Transplantation of this 3D tissue in the future could help patients with visual impairments see clearly.

“This is an important milestone for a new generation of regenerative medicine,” says senior study author Yoshiki Sasai of the RIKEN Center for Developmental Biology. “Our approach opens a new avenue to the use of human stem cell-derived complex tissues for therapy, as well as for other medical studies related to pathogenesis and drug discovery.”

During development, light-sensitive tissue lining the back of the eye, called the retina, forms from a structure known as the optic cup. In the new study, this structure spontaneously emerged from human embryonic stem cells (hESCs) — cells derived from human embryos that are capable of developing into a variety of tissues — thanks to the cell culture methods optimized by Sasai and his team.

The hESC-derived cells formed the correct 3D shape and the two layers of the optic cup, including a layer containing a large number of light-responsive cells called photoreceptors. Because retinal degeneration primarily results from damage to these cells, the hESC-derived tissue could be ideal transplantation material.

Beyond the clinical implications, the study will likely accelerate the acquisition of knowledge in the field of developmental biology. For instance, the hESC-derived optic cup is much larger than the optic cup that Sasai and collaborators previously derived from mouse embryonic stem cells, suggesting that these cells contain innate species-specific instructions for building this eye structure. “This study opens the door to understanding human-specific aspects of eye development that researchers were not able to investigate before,” Sasai says.

The anniversary issue containing Sasai’s study will be given to each delegate attending the 2012 ISSCR meeting in Yokohama, Japan. To highlight the ISSCR meeting and showcase the strong advances made by Japanese scientists in the stem cell field, the issue will also feature two other papers from Japanese authors, including the research groups of Akira Onishi and Jun Yamashita. In addition, the issue contains a series of reviews and perspectives from worldwide leaders in stem cell research.