Ten 2011 Research Discoveries

Thanks to generous FFB donors, Canadian researchers continue to move us closer to treatments for retinal degenerative diseases. Here are ten discoveries FFB-funded scientists made this year.

1) Specialized nerve cells in the eye allow us to detect motion

Dr. Gautam Awatramani at Dalhousie University in Nova Scotia studies the “electrical wiring” that allows the eye to send visual messages to the brain. This year, he and his team made new discoveries about specialized neurons that respond to movements in four directions – up, down, right, left – and help us understand the moving world around us. Dr. Awatramani and his team study this wiring in the hopes of re-programming it to respond to new signals from light-sensitive molecules placed in the eye. If successful, this strategy might one day restore vision to people who have lost their photoreceptors to retinal eye disease. Published: August 2011 in Neuron

2) New strategies can improve the diagnosis of Bardet Biedl Syndrome

This year, Dr. Elise Héon and her team at the Hospital for Sick Children published the most comprehensive study ever done of families with Bardet Biedl syndrome (BBS). In total, 83 families were involved. BBS is an inherited condition that affects many parts of the body, as well as the eye. This exhaustive study showed that some of the “classic” symptoms were less common than previously believed, while others were more common. This knowledge gives physicians better guidance for diagnosing their patients. As well, the detailed analysis of the genetic mutations found in these families has identified the most common mutations involved and led to a new, efficient and cost-effective strategy to improve genetic testing for BBS. Published: Sept 2011 in Ophthalmic Genetics and June 2011 in Human Mutations

3) Some autosomal dominant retinitis pigmentosa is due to impaired RNA splicing

To develop therapies for genetic diseases, scientists need to understand how those genetic changes cause vision loss. This year, Dr. Jim Hu, and his colleague Dr. Robert Molday, have discovered new mechanisms responsible for some types of autosomal dominant retinitis pigmentosa. The affected genes, PRPF3, PRP31 and PRP8, play a role in how genetic information is translated from our genes to make things happen within the cell. Mutations in these genes impair a process called RNA splicing. Gene translation and RNA splicing are necessary functions for all cells in the body. However these genes cause eye disease because of the flurry of activity that happens every day in our retinas. The retina is the most metabolically active part of the body, so, over time, errors in this process begin to impair vision.
Published: January 2011 in PLoS One.

4) Vision loss due to diabetic retinopathy might be reduced with newly discovered substance

This year, a groundbreaking study helped explain why conditions like diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusions cause blindness. These conditions occur when blood flow in some area of the retina is insufficient, depriving it of oxygen and ultimately destroying its ability to sense light and send visual information. This team has shown that a substance called semaphorin 3A, which is secreted by oxygen-starved tissues, prevents blood flow from being restored to this area. Blocking the actions of this substance might restore blood flow in the deprived areas more quickly, allowing the retina to recover and saving vision.  Karine Zaniolo, a FFB Post-Doctoral Fellow, was part of this team led by Dr. Sylvain Chemtob at McGill University.  
Published: June 2011 in Blood

5) Canadian clinical trial for Leber congenital amaurosis (LCA) shows promising results

This year, Dr. Robert Koenekoop of McGill University presented promising findings from a trial of an oral drug being developed by the Vancouver-based biotech company QLT Inc. The drug is a potential treatment for people with either retinitis pigmentosa or Leber congenital amaurosis (LCA, a blinding disease of childhood), whose eye disease is due to mutations in the LRAT or RPE65 genes. One year after a single course of treatment, the vision of 8 of 12 trial participants with LCA showed significant improvements. For more details see our news story on this trial. Although the FFB has no direct role in funding this trial, previous FFB funding of Dr. Koenekoop developed the technology that helped made it possible.
Presented: May 2011, Association for Research in Vision & Ophthalmology Meeting

6) A Helper-Dependent Adenovirus (HD-Ad) can be used to deliver large gene therapies

In 2007, the first gene therapy for one type of Leber congenital amaurosis (LCA) was tested in clinical trials. Since then, several research teams have begun work to develop gene therapies for other conditions. One challenge is the size of the mutated gene that needs to be replaced. While the mutated gene in the original LCA trial was small, many of the mutations that cause retinal eye diseases are larger. This year, Dr. Jim Hu at the University of Toronto showed that a virus called a helper-dependent adenovirus (HD-Ad) could be used to carry larger genes into the targeted cells. This virus could be used to develop therapies for Stargardt disease, as well as some types of retinitis pigmentosa and LCA.
Published: April 2011 in Cell and Bioscience

7) Combining modestly effective therapies for retinitis pigmentosa can improve treatment outcomes

Several kinds of therapies for retinitis pigmentosa and other inherited retinal degenerative diseases are now in development. Some aim to correct the genetic defects which cause disease, while others aim to stop or slow cell death, an approach often referred to as neuroprotective therapy. This year, Dr. Kevin Gregory-Evans and his team at the University of British Columbia (UBC) treated rats that had a type of autosomal dominant RP, with a combination of two therapies. One was a neuroprotective therapy developed in the Gregory-Evans lab, and the second was a genetic therapy now being tested in people with cystic fibrosis. Rats treated with the combination therapy had much better outcomes than rats treated with either therapy alone; in fact, their retinas were indistinguishable from those of rats with normal vision. While this specific project was not directly funded by the FFB, it is an important proof-of-principle for a whole group of studies on combination vision therapies now being funded at UBC, jointly by the FFB and the Canadian Institutes of Health Research (CIHR). Published: June 2011 in Ophthalmic Research.

8) The survival of retinal cell transplants can be improved

Vision loss happens in people with retinal eye disease because critical light-sensitive photoreceptors in the retina die through a process called apoptosis. Dr. Catherine Tsilfidis at the Ottawa Hospital Research Institute is leading an international team of researchers studying how XIAP (x-linked inhibitor of apoptosis) gene therapy might be used to halt apoptosis, preserving vision. This has already proven successful in animals, and Dr. Tsilfidis and her team are now working toward human trials. This year, the team demonstrated that XIAP gene therapy might also have another use – to improve the efficacy of stem cell therapy. While several researchers, including Dr. Derek van der Kooy, University of Toronto, and Dr. Gilbert Bernier, Université de Montréal, have shown that stem cells can be used to create new rod and cone photoreceptors for transplantation (in animals), only a tiny portion of these cells (~1%) survive the process. Dr. Tsilfidis’ colleague, Dr. David Zacks, demonstrated that pre-treating cells with XIAP gene therapy could significantly improve cell survival.
Published: March 2011 in Investigative Ophthalmology and Vision Sciences

9) Skin cells can be used to reconstruct the retina restoring vision in mice

Only a few years ago, Japanese scientists showed that adult skin cells could be prompted to produce stem cells. The resulting cells are called “induced pluripotent stem cells”, or ipSCs. This exciting revelation offered hope that perfectly matched cells – cells whose genetic make-up is identical to that of the transplant-recipient – could be easily collected from the skin of that and used to replace any damaged organ, without the risk of immune rejection. Now, researchers are beginning to make this hope a reality. This year, for the first time, scientists used ipSCs derived from skin cells to reconstruct the retina and thereby to restore vision in mice. Dr. Budd Tucker, a FFB-funded Post-Doctoral Fellow originally from Memorial University of Newfoundland, was the lead author on this study. Published: May 2011 in PLoS One.

10) People who have lost most of their vision may still have salvageable photoreceptors

Do people with severe visual impairments still have some photoreceptors that might be saved with effective treatment? Research by Dr. Robert Koenekoop of McGill University and his Dutch colleagues suggests that the answer is yes, at least for people with some types of Leber congenital amaurosis (those with gene defects in GUCY2D, SPATA7, RPE65 or LRAT genes). They found that some people with severe visual impairment due to these conditions still had structurally sound photoreceptors that were able to process nutrients normally. This finding is exciting because it means that treatment with some of the gene or pharmaceutical therapies now being tested in clinical trials might be a possibility even for people at more advanced stages of disease. Dr. Koenekoop and his colleagues continue to work to better define how long photoreceptors remain intact and how this may vary depending on the mutation involved.
Presented: May 2011 in Association for Research in Vision & Ophthalmology Meeting

Donors like you made these findings possible!

FFB donors are a crucial part of every scientific discovery – don’t underestimate the impact of your donation. In 2011, your donations helped funded 25 research teams across Canada; 18 of these projects are still ongoing and still need your support. As well, an unprecedented number of new projects have already been brought to us for funding in 2012.  What can be funded depends on donors like you. Your donation will enable FFB funded scientists to continue sight-saving research, creating a new future for people living with vision loss.

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