Des cornées biosynthétiques implantées chirurgicalement ont permis de restaurer en partie la vue de certains patients.
     Des cornées biosynthétiques implantées chirurgicalement ont permis de restaurer en partie la vue de certains patients, selon un petit essai clinique de deux ans conduit en Suède dont les résultats sont publiés mercredi aux Etats-Unis. Cette étude menée avec dix participants, a montré que l'implantation de cette cornée biosynthétique faite de collagène humain recombiné selon un procédé mis au point par la firme de biotechnologie américaine FibroGen, a contribué à régénérer et à réparer les tissus oculaires endommagés.

New Rochelle, NY, August 13, 2010
     The easy accessibility of the eye and the established link between specific genetic defects and ocular disorders offer hope for using gene therapy to provide long-term therapeutic benefit. Two reports in the current issue of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com), describe the effective replacement of a human gene to preserve photoreceptor function in a mouse model of severe retinal degeneration. The articles are available free online (www.liebertpub.com/hum).
     Basil Pawlyk and colleagues from Harvard Medical School and Massachusetts Eye and Ear Infirmary (Boston, MA) delivered the human gene for RGPR-interacting protein-1 to mice affected with Leber congenital amaurosis (LCA), a condition linked to a mutated form of RPGRIP1 that causes degeneration of photoreceptors in the eye. The researchers packaged the gene in an adeno-associated virus (AAV) vector and injected the vector under the retinas of the affected mice. They demonstrated expression of the human gene in the photoreceptors, with correct localization to the cilia. Further evaluation revealed improved function and survival of the photoreceptors in the treated eyes.
The authors conclude that the results of this study, presented in the paper entitled, "Replacement Gene Therapy with a Human RPGRIP1 Sequence Slows Photoreceptor Degeneration in Murine Model of Leber Congenital Amaurosis," validate a gene therapy design that could serve as the basis for a future clinical trial in patients affected by this form of LCA.
     In the same issue, Kamolika Roy, Linda Stein, and Shalesh Kaushal from University of Massachusetts Medical School (Worcester) review the use of recombinant AAV vectors for gene therapy to treat ocular diseases. Based on the success of three early-stage clinical trials in LCA, they conclude that this approach appears "to be a safe, effective, and long-term treatment for LCA, a previously untreatable disorder." In the article, "Ocular Gene Therapy: An Evaluation of Recombinant Adeno-Associated Virus-Mediated Gene Therapy Interventions for the Treatment of Ocular Disease," they conclude that rAAV-mediated gene therapy is "the most suitable gene therapy treatment approach for ocular diseases."
     "The successful correction of this photoreceptor defect in a relevant mouse model of LCA should usher in a new wave of translational research in retinal degeneration syndromes," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Head of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, in Philadelphia.
     Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies is an authoritative peer-reviewed journal published monthly in print and online that presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Tables of content and a free sample issue may be viewed online (www.liebertpub.com/).

http://www.liebertonline.com/1
http://www.liebertonline.com/2

free access 
Ocular Gene Therapy: An Evaluation of Recombinant Adeno-Associated Virus-Mediated Gene Therapy Interventions for the Treatment of Ocular Disease
Kamolika Roy, Linda Stein, Shalesh Kaushal
Human Gene Therapy. August 2010, 21(8): 915-927.

This review summarizes the current progress and future prospects of recombinant AAV (rAAV)-mediated gene therapy interventions/applications for a wide variety of ophthalmologic disorders.

Abstract:
Both gene replacement therapy and alteration of host gene expression are playing increasingly important roles in the treatment of ocular diseases. Ocular gene therapy may provide alternatives to current treatments for eye diseases that are either greatly invasive and thus run the risk of complications, that offer only short-term relief from disease symptoms, or that are unable to directly treat vision loss. The success of three separate phase I clinical trials investigating a gene therapy intervention for the treatment of the retinal degenerative disorder Leber's congenital amaurosis (LCA) has unveiled the therapeutic potential of gene therapy. Preliminary results have demonstrated ocular gene transfer, using nonpathogenic recombinant adeno-associated viral (rAAV) vectors specifically, to be a safe, effective, and long-term treatment for LCA, a previously untreatable disorder. Nonpathogenic rAAV vectors offer the potential for long-term treatment. Many of the genes implicated in human ocular diseases have been identified, and animal models for such diseases have been developed, which have greatly facilitated the application of experimental rAAV-mediated gene therapy. This review highlights the key features of rAAV-mediated gene therapy that make it the most suitable gene therapy treatment approach for ocular diseases. Furthermore, it summarizes the current progress of rAAV-mediated gene therapy interventions/applications for a wide variety of ophthalmologic disorders.

     Cécité, infarctus et même infertilité, il pourrait bientôt être possible de traiter de nombreuses maladies à l'aide d'une greffe de cellules. Les premiers essais sont encourageants.
     Eviter la cécité par une greffe de cellules? L'idée est séduisante et elle ne tient plus tout à fait de la science fiction. Aux Etats-Unis, cette thérapie cellulaire pourrait bientôt être testée chez l'homme. Le principe? Remplacer les cellules abîmées de la rétine dans certaines maladies de l'œil par des cellules saines, obtenues à partir de cellules souches embryonnaires (ES). Une source prolifique de cellules de rechange!
     Issues d'embryons de 5 à 7 jours, les cellules souches embryonnaires sont en effet capables de se multiplier à l'infini. Et surtout, elles peuvent se différencier en n'importe quel type cellulaire: cellule cardiaque, rétinienne, neurone. D'où l'idée de les utiliser pour réparer les tissus abîmés. Cette "thérapie cellulaire" a déjà été testée dans plusieurs maladies. A commencer par une pathologie de l'œil: la dégénérescence maculaire liée à l'âge.
     L'œil est une des premières cibles pour ce type de greffe car il est peu vascularisé. Le risque de réaction immunitaire et de rejet de greffe est donc plus faible que pour un autre tissu. L'approche développée par la société américaine Advanced Cell Technology consiste à remplacer les cellules rétiniennes qui dégénèrent, dites cellules de l'épithélium pigmentaire. Ces dernières permettent aux neurones rétiniens de bien fonctionner, notamment en nettoyant les poussières dans la rétine.
     Une étude a été menée chez des rats souffrants de dégénérescence maculaire liée à l'âge et chez des souris atteintes de la maladie de Stargardt, deux pathologies qui conduisent à la cécité. Les scientifiques ont poussé des cellules souches embryonnaires humaines à se différencier en cellules de l'épithélium pigmentaire. Puis ils ont implanté ces cellules dans les rétines lésées de ces animaux. Elles ont permis d'éviter la disparition des cellules qui détectent la lumière, les photorécepteurs.
     Après trois mois, les rongeurs traités disposaient de 5 à 6 couches de photorécepteurs, tandis que les rats non traités n'avaient plus qu'une seule couche de photorécepteurs et étaient quasiment aveugles. La vision des premiers avait été préservée. Forte de ce succès, Advanced Cell Technology vient d'annoncer qu'elle commencerait dans quelques mois un essai de cette technique chez l'homme.
     Malgré tout, des doutes demeurent. "Il faudrait vérifier sur de plus longues périodes que les cellules greffées ne forment pas de tumeurs, avant de passer à des études sur l'homme ", appuie José-Alain Sahel, directeur de l'Institut français de la vision.
     L'application de la thérapie cellulaire au traitement des infarctus est bien plus avancée : la greffe de cellules souches embryonnaires est déjà testée chez le singe rhésus, beaucoup plus proche de l'homme que le rongeur.
     Si quelques milliers de cellules rétiniennes peuvent suffire pour tenter de rendre la vue à un patient, il faut plusieurs centaines de millions de cellules musculaires cardiaques pour restaurer un cœur malade. La difficulté est d'obtenir in vitro une grande quantité de cellules cardiaques et de les transplanter sans endommager leur capacité à se contracter.

Abstract

Work on stem cells is one of the hottest research areas in biology. But are such studies of any therapeutic value? Fortunately, yes, as is evident from successes in treating blindness.

By Courtney Humphries
Thursday, June 03, 2010

     Scientists have created a three-dimensional, retina-like structure out of human embryonic stem cells that they hope could someday serve as a retinal transplant for people with macular degeneration and other diseases of the retina. Their method, published recently in Journal of Neuroscience Methods, offers a potential new source of cells for retinal transplants.
     Hans Keirstead, lead author of the paper and a stem cell biologist at University of California, Irvine, says that the method is designed to provide an alternative to human fetal tissue transplants, which have been conducted on a small group of patients and have resulted in improved vision. Fetal cells are difficult to obtain and raise ethical issues. "We really wanted to build upon that technique by creating a renewable source of tissue," he says.
     In this study, the researchers first created two types of cells from the human embryonic stem cells: early-stage retinal cells, and retinal pigment epithelium (RPE) cells, which provide nourishment to the cells responsible for vision in the retina. The researchers then grew these two types of cells together in a chamber designed to expose them to a gradient of concentrations of solutes and growth-promoting chemicals. The cells could form three-dimensional structures, a feat rarely achieved with stem cells.
          Keirstead believes that the study points to two important strategies for creating retinal transplants: growing early retinal cells along with RPE cells, and bathing the cells in a gradually changing solution that encourages the development of three-dimensional layers of cells. His team found that this approach generated early-stage retinal cells that were on the path of differentiating into all of the various cell types in the retina.
     Keirstead believes that a retinal transplant will work best when made of cells that have not fully developed. "The three-dimensional layer is purposefully young," he says. Previous studies have found that younger cells are more likely to integrate with existing tissue after transplantation, rather than die.

     Of all the complications of diabetes, few are as devastating as diabetic retinopathy, a progressive eye disease that causes blurred vision and in some patients, blindness. By the time most patients recognize something's wrong, it's often too late for them to be treated effectively. As a result, diabetes is the leading cause of vision loss among adults over 20. More than 12,000 new cases of blindness each year are caused by diabetic retinopathy, according to the National Institutes of Health.

Eye sight: White dots a patient's retina (top) are early signs of disease. In the image below these spots are identified automatically.
Credit: Ken Tobin

     An ophthalmologist and a scientist from the Department of Energy's Oak Ridge National Laboratories in Tennessee believe they can help doctors detect diabetic retinopathy long before the disease wreaks havoc on their patients' vision. Their startup company, Automated Medical Diagnostics (AMDx), has developed software that can detect the early signs of diabetic retinopathy by comparing digital photos of a patient's retina to images that represent various stages of diabetic eye disease. AMDx's founders believe their technology will enable all health workers--even those who are not trained in eye care--to take retinal scans of any patient, zap them over the Internet to AMDx's servers, and get a diagnosis back before the patient leaves the office. "We're trying to show we can be as accurate as a trained ophthalmologist," says Ken Tobin, AMDx co-founder and division director of measurement science and systems engineering at Oak Ridge.
     AMDx's technology was inspired by a system that Oak Ridge scientists originally developed to help semiconductor manufacturers analyze defects in computer chips. Their software essentially teaches computers a technique called "content-based image retrieval." The system can take a single image of a chip and then sort through giant databases of other images to find similar visual patterns--a process that some chipmakers now use to spot problems and improve manufacturing methods.
     In 2005, Tobin met Edward Chaum, an ophthalmologist and professor at the University of Tennessee's Hamilton Eye Institute in Memphis. "Less than half of diabetics are screened in any given year for retinopathy, despite the fact that they are told they need regular eye exams," Chaum says. Many patients don't have health insurance, he says, or they just don't want the hassle of traveling to see yet another specialist. But Chaum and Tobin realized that if primary care doctors could do basic eye screenings on diabetic patients, they might catch many more cases of retinopathy than are being detected today.
     The retina is particularly well suited to content-based image retrieval, Tobin says. Unlike other types of medical images, such as brain scans and mammograms--which are highly variable and require multiple images to create a three-dimensional effect--the retina is virtually two-dimensional and similar from one photo to another. (...)

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» Molecular Sunglasses for Macular Degeneration:

     Thousands of people who are partially-sighted following stroke or brain injury could gain greater independence from a simple, cheap and accessible training course which could eventually be delivered from their mobile phones or hand-held games consoles, according to a new study.
     The new research has found that a computer-based technique developed and assessed by Durham University improved partially-sighted people's ability to "see" better. It may eventually improve and broaden the portfolio of rehabilitation techniques for partially-sighted patients.
     The study, published in the academic journal Brain, tested the technique on patients who suffer from a condition affecting their sight called hemianopia. 
     Hemianopia affects over 4,000 people in the UK each year. Sufferers lose half of their visual field due to stroke or other brain injury. They are heavily dependent on others as they struggle with balance, walking, finding things around the house, and they are not normally able to drive. 
     The research was funded by the Medical Research Council, Economic and Social Research Council, and supported by the charity Action for Blind People.
The study, which tested patients' visual ability before and after the training, found that patients became faster and more accurate at detecting objects, such as coloured dots or numbers, on a computer screen. 
     The researchers believe the test helped patients to compensate for their lost vision by exploring their ‘blind field' more, which is the part of the visual field affected by the brain damage. Further research is needed to pinpoint exactly why the technique helps patients to "see" better but the scientists believe it is likely due to improved attention, concentration and awareness of their visual problems.
     The study findings offer hope that people who receive regular training like this could live more independently in their day-to-day lives because their visual ability would be improved.
      Lead researcher, Dr Alison Lane, from Durham University's Psychology Department, said: "This research shows us that basic training works in getting people to use their "poor" visual side better. 
     "Although we are not yet sure why this happens, we think it might be because training increases their attention, concentration and awareness of their "blind" field. 
     "We think attention is key in improving people's abilities to use their limited vision."
     She added: "This simple technique is a very viable rehabilitation option and in future could be easily accessible at low cost to everyone who needs it."
Currently, there is no widely available treatment for people who experience visual loss following brain damage because of the lack of scientific evidence that existing therapies are effective, according to the study authors.
     The Durham study compared two types of rehabilitation techniques – one focused on exploration and the other on attention.  Neither training option is currently available on the NHS although alternative training programmes can be bought privately.
     The research, which tested 46 patients, found that the basic attention training without the need for patients to move their eyes extensively was for the most part as effective at rehabilitation as the more specialised exploration technique.

CASE STUDY – Nichola Burlison from Low Willington, County Durham*
     Nichola Burlison, who is married with two young children, has hemianopia. Nichola, who is 31 years old, suffered severe brain damage after a car accident eight years ago. 
     She spent six months in hospital and had to re-learn all basic skills such as walking, talking, dressing and eating.  After contact with Action for Blind People, Nichola took part in Durham's research.
     She said: "The training has made a big difference to me.  Although I still struggle with basic things like crossing the road, reading, cooking, I feel so much more confident.  I am more comfortable with reading and I don't miss words at the start of sentences anymore.  I also move my eyes around, both to the left and right, because I am more aware that I can do that.
     "I was really surprised that I could do more than I thought after the training.  It gave me a big boost and I would love for other people in my position to become aware of this as it may help them too.
     "I wish I had time to keep on doing the training more often but it is tricky with two little ones in the house.  If the software was available on a games console or something like that, it would be a huge benefit to me because I could spend a quick five minutes here and there on my way to work or on my lunch break."

* Please note that we are not able to give any further biographical details due to the nature of the case study's employment.

FACTS ABOUT HEMIANOPIA
    * Hemianopia is a type of homonymous visual field defect, which means people lose vision on the same side in both eyes.
    * The translation for hemianopia is "half blindness".
    * Hemianopia is caused by injury to the brain itself such as from stroke or trauma.  It can also be as a result of certain surgical procedures, or a tumour in the visual processing part of the brain.
    * There are 4,271 cases of hemianopia diagnosed annually in the UK, and 230 cases a year in the North East.

http://www.durham.ac.uk/news
Full bibliographic information
    * Visual exploration training is no better than attention training for treating hemianopia, Lane et al, published by Oxford Journals in Brain, April 2010.