New Grants Approved 2009 - 2010
Partnerships with the Canadian Institutes of Health Research
Eye Stem Cells: Biology and Therapeutic Applications – Sun Life Financial
Primary Investigator: Valerie Wallace, Ottawa Hospital Research InstitutePer Fagerholm, Linköping University, Sweden
May Griffith, Ottawa Hospital Research Institute, University of Ottawa
Bernard Hurley, Ottawa Hospital
Derek van der Kooy, University of Toronto
Carol Schuurmans, University of Calgary
Vincent Tropepe, University of Toronto
Ottawa Hospital Research Institute
Granted: $2.4 million over 5 years, January 2009 - December 2013
Funded by: CIHR - Regenerative Medicine and Nanomedicine, FFB, Sun Life Financial
Stem cell therapies have the potential to benefit more than one million Canadians affected by degenerative eye diseases, such as retinitis pigmentosa, age-related macular degeneration and corneal diseases; all of which cause blindness. By replacing cells that have been lost through disease or injury, stem cell therapies could potentially benefit anyone, at any stage of eye disease.
Together the team hopes to develop better methods for controlling stem cells, so that they can coax these cells into producing different kinds of eye cells, such as retinal and corneal cells. This is currently the greatest obstacle to successful stem cell therapies. They will also develop more efficient transplantation methods that help new eye cells integrate with existing tissue to restore lost vision. And they will work towards combining cells, genes, biomaterials and pharmaceuticals to create an improved artificial cornea.
Novel Gene Therapy Approaches for the Treatment of Retinal Degenerative Diseases
Primary Investigator: Robert Molday, University of British ColumbiaJim Hu, University of Toronto
Bill Hauswirth, University of Florida
Robert Koenekoop, McGill University
Marinko Sarunic, Simon Fraser University
University of British Columbia
Granted: $3 million over 6 years, January 2009 - December 2014
Funded by: CIHR - Regenerative Medicine and Nanomedicine, FFB
The application of gene therapy for retinal degenerative diseases will be investigated in Stargardt macular dystrophy, cone-rod dystrophy, Leber congenital amaurosis (LCA), and retinitis pigmentosa (RP). The strategy is to replace the defective gene with a “new healthy gene” in specific animal models for retinal degenerative diseases with the aim of slowing photoreceptor loss and partially restoring vision. Success in these animal models would lead to future human clinical trials. The recent success in gene therapy for RPE65 has been highly conclusive for LCA; we believe that we can learn from this and advance even more quickly this time.
XIAP Gene Therapy for the Treatment of Retinal Degeneration
Primary Investigator: Catherine Tsilfidis, Ottawa Hospital Health ResearchRobert Korneluk, University of Ottawa
William Hauswirth, University of Florida
David Zacks, Kellogg Eye Center and the University of Michigan
Stuart Coupland, University of Ottawa Eye Institute
Brian Leonard, University of Ottawa Eye Institute
Ottawa Hospital Health Research
Granted: $1.4 million over 5 years, January 2010 - December 2015
Funded by: CIHR - Institute of Aging, FFB, Jean Boddy and Jim & Colleen Pallister, Scotiabank
Previously funded by FFB: $40,000 over 6 months, July 2009 - December 2009
The goal of this project is to begin testing a new gene therapy in patients, who are losing their vision due to retinal disease, by the end of five years. Dr. Tsilfidis and her team have shown that a gene called XIAP can block this process and prevent retinal cell death. The gene can be delivered to the eye using a virus called Adeno-Associated Virus (AAV). This therapy has proven particularly promising in an experimental model of retinitis pigmentosa, a genetic condition and important cause of blindness in which a large portion of the outer layer of the retina is lost. XIAP gene therapy was able to protect the cells of this critical part of the eye from dying, resulting in significant preservation of vision.
Operating Grants
Gautam Awatramani
Dalhousie UniversityProbing and Repairing Circuits During Retinal Degeneration
Granted: $90,000 over 1 year, July 2009 - June 2010
Dr. Awatramani is leading a team to test and design strategies to restore vision in people already blind from retinal degeneration. The focus is on probing and repairing circuits during retinal degeneration. Dr. Awatramani is part of a team that partially restored vision in animals that were otherwise completely blind from inherited retinal degeneration (Lagali et al., 2008). This breakthrough revealed the importance of reprogramming surviving, non-photoreceptive retinal neurons to be light-responsive.
Outcomes of the research include a better understanding of the bipolar cells (neurons that normally relay signals from rods and cones) and what is most effective way to make them respond beneficially. Light sensitivity, kinetics and responses in animals with restored vision will be measured for development of new treatment theories and pre-clinical tests.
Michel Cayouette
Institut de recherches cliniques de MontréalSpecification of temporal identity in retinal progenitor cells
[Renewal] Granted: $80,000 over 1 year, July 2009 - June 2010
Stem cells are promising source of replacements for photoreceptors lost through degeneration. But to design safe and efficient cell replacement therapies, researchers need to understand the mechanisms that guide formation of the various retinal cell types during normal development. Recently discovered Ikaros, a gene expressed in early retinal progenitor cells; test whether or how it is critical for generating early-born neurons (e.g., photoreceptors).
This will be done through genetically engineered mice (Ikaros-reporter, and mutant (gene-trap) of related gene Pegasus, both already created and in use in his lab); and through gene expression-profiling with gene “chips”.
Gilbert Bernier
Maisonneuve Rosemont HospitalStem Cell Transplantation for the Treatment of Retinal Degenerative Disease
[Renewal] Granted: $50,000
In RP and AMD, replacement of lost photoreceptors is one potential way to stop disease progression and restore visual function. Human embryonic stem cells can be expanded and manipulated in culture to produce specific cell types, and recent work revealed that post-mitotic photoreceptor precursors from newborn mice could functionally integrate the retina of adult mice. The goal here to differentiate pluripotent hES cells into photoreceptors in the test tube and test their therapeutic potential in animal models of retinal degeneration.
Bernier and his team will grow hES cells in novel cell culture conditions and inducing them to become rods and cones, by applying chemical factors known to do this; also enhancing survival by engineering them to make their own survival factors; testing integration of transplants with microscopy and electrophysiology.
Robert Koenekoop
McGill UniversityIdentifying novel Leber congenital amaurosis genes using novel strategies
[Renewal] Granted: $50,000 over 1 year, July 2009 - June 2010
This project will identify new genes and mutations responsible for Leber congenital amaurosis (LCA), the severest human retinal dystrophy and the most common cause of inherited childhood blindness.
Dr. Koenekoop will explore genes that encode for proteins known to interact with the protein, lebercilin, encoded by the gene in which mutations cause LCA5 (“the lebercilin interactome”) as well as other proteins involved in structure and maintenance of the photoreceptors’ ciliary backbone (the “ciliary proteome”), to identify new LCA candidate genes.
Graduate Student Scholarships
Elizabeth M. Kita
FFB and Alberta Heritage Foundation for Medical Research (AHFMR) PartnershipUniversity of Calgary
Supervisor: Sarah McFarlane, Ph.D.
The Expression and Function of Class 3 Semaphorins in the Developing Retina
Awarded: $100,000 over 5 years, January 2010 - December 2015
Blindness can be caused by damage to retinal cells that link the eye to the brain, as in glaucoma. But there is hope that sight might be restored by replacing the damaged cells and by guiding them to make the right connections in the brain. Under the supervision of Prof. Sarah McFarlane, Ms. Elizabeth Kita is studying proteins called semaphorins, which act like signs to direct these connections during development. By learning to read these signs and understand how they work, we might use them to guide re-growth of eye-brain connections and thus restore vision in many blind people.
Ongoing Grants
Operating Grants
Rod Bremner - Estate of Olga Variollo
University Health Network
Mechanism of protection of retinal cells by p107 and p27
[Renewal] Granted: $300,000 over 3 years, July 2008 – June 2011
This project is a renewal of Dr. Bremner’s project, Role of Rb Effector Genes in Retinal Development. He and his team have found previously that proteins in the Rb and p27 family are necessary for the survival of rod and cone photoreceptors. Understanding how they promote survival has potential benefits for the treatment of retinal diseases where these cell types die, such as in retinitis pigmentosa. The proposed studies will determine whether it is the Rb-like or p27-like activity of p107 that is most critical for photoreceptor survival, and thus provide a clearer picture of what is required to protect photoreceptors from death. This kind of knowledge may suggest new therapies to protect these vital cells from dying, in humans with a blinding disease.
David D. Eisenstat
University of Manitoba
Role of DLX homeobox genes in retinal development
Granted: $180,000 over 3 years, July 2008 – July 2011
Dr. Eisenstat and his team will study DLX homeobox genes (a type of transcription factor), which are genes involved in regulating the development of the mouse retina.
Dr. Eisenstat will explore whether these DLX transcription factors block the development of photoreceptors in retinal progenitors while at the same time promoting ganglion cell fate and survival. He will also examine mice missing only one DLX gene rather than two, to determine whether DLX1 or DLX2 is more important for normal retinal development. He will also identify all of the genes directly controlled by DLX transcription factors during retina development. It is important to understand the mechanisms of retinal development in a mouse model to uncover the causes of retinal disease.
Alan Jeffrey Mears
Ottawa Hospital Research Institute
Genetic and functional analysis of novel cone photoreceptor genes
Granted: $100,000 over 2 years, July 2008 – June 2010
Dr. Mears at the Ottawa Hospital Research Institute is conducting a study in mice, whose photoreceptors have been drastically altered. This will provide the means to identify those genes that are critical for photoreceptor development. Photoreceptors are the rods and cones that capture light thereby initiating the process of vision.
The rods, which greatly outnumber the cones, do not give high visual acuity (sharp or clear vision). Rods are highly sensitive and enable us to see in the dark. The cones, which in humans are primarily concentrated in the central area of the retina, referred to as the macula and fovea, only function under bright light conditions and are responsible for sharp central vision and the perception of colour. There are many diseases which impact the retina and in most cases it is ultimately the loss of these photoreceptors that results in the impairment of vision or blindness.
By manipulating key genes that control photoreceptor development, the goal is to turn retinal stem or progenitor cells into new healthy photoreceptors that may be transplanted into diseased retinas of mice. If successful, such transplantation therapies could preserve or even restore vision in patients with retinitis pigmentosa, Leber’s congenital amaurosis, cone dystrophies and age-related macular degeneration.
David Picketts
Ottawa Hospital Research Institute
Epigenetic regulation of interneuron homeostasis in the mammalian retina
Granted: $270,000 over 3 years, July 2008 – June 2011
Dr. David Picketts and Dr. Valerie Wallace at the Ottawa Hospital Research Institute are studying how the Atrx gene promotes the health and survival of interneurons in the mouse retina.
Amacrine and horizontal cells are interneurons in the retina whose function is to process information from photoreceptors before it is sent to the brain and transmitted as an image. These interneurons must remain intact and receptive to continued photoreceptor signals during treatment to restore vision, however, very little is known about how the health of these cells is maintained.
Many studies examine how transplanted cells during cell transplantation or gene therapy will survive and replenish the photoreceptors, but less is known about how they establish new connections with the remaining retinal neurons.
Mice that lack the Atrx gene in the retina lose a significant proportion of their amacrine and horizontal cells after birth. By identifying the Atrx-dependent pathways and genes that promote survival of these cells, we will gain insight into how the retinal circuitry is maintained. Understanding the biology underlining the maintenance of these cells could improve the outcome of gene and cell therapy to the eye.
Christian Salesse
Université Laval
Molecular determinants responsible for the involvement of lecithin retinol acyltransferase, a protein of the visual cycle, in retinitis pigmentosa
Granted: $100,000 over 2 years, July 2008 – June 2010
The sensation of vision is initiated by the absorption of light by visual pigments in rod and cone photoreceptors. After this has occurred, the part of the visual pigment that is derived from Vitamin A must be regenerated, so that it can perform the same function again. This is done through a series of enzymatic reactions called the visual cycle. Mutations of several of the enzymes of the visual cycle lead to retinal degeneration. One of these enzymes is a cell membrane protein called lecithin retinol acyltransferase (LRAT).
A particular mutation of LRAT leads to the loss of its enzyme activity and causes retinitis pigmentosa. However, this mutation does not impair the enzymatic activity of LRAT. Very likely, this mutation causes loss of function either by altering binding of the mutant enzyme to the cell membrane, or by drastically changing the three-dimensional structure of the enzyme. Dr. Salesse and his team at the CHUQ research center of Laval University will test these hypotheses, by comparing the membrane-binding activity and the structure of the native (normal) LRAT enzyme with those of the mutant enzyme.
This study will enhance our knowledge of a relatively unknown family of enzymes that are crucial for retinal function. Understanding how mutation of LRAT leads to malfunctioning of the retina, is essential for developing therapies to prevent this form of RP.
Vincent Tropepe
University of Toronto
Genetic & molecular studies of neurogenesis and regeneration in the zebrafish
Granted: $150,000 over 3 years, July 2008 – July 2011
Dr. Vince Tropepe of the University of Toronto will use the natural ability of zebrafish to regenerate retinal cells under normal and pathological conditions in order to investigate the genetic basis for tissue self-repair in the retina.
The zebrafish can regenerate all of the specialized cells in the retina, including photoreceptors (rods and cones), unlike adult human retina, which cannot naturally produce new specialized cells to replace those that are lost or damaged by diseases, such as RP, AMD, glaucoma. On almost all other levels of organization and function, the fish retina and the human retina are similar. Recent discovery of stem cells in the adult human retina suggests that there might be a hidden capacity for regeneration if researchers can find a way to properly stimulate and control them.
The goal of the research is to gain clear understanding of the molecular mechanisms controlling retinal cell regeneration. This research will provide an important foundation for investigating whether similar mechanisms can be stimulated in the human retina, which may lead to new cell-based therapies to treat retinal degenerative diseases.
Orson Moritz
University of British Columbia
Mechanisms of Secondary Cone Degeneration in RP
Granted: $70,000 for 3 years, July 2006 – June 2010
Dr. Moritz and his team have developed a frog model of inherited retinal degeneration, in which rod cell death can be initiated at any time. This animal acts as an excellent model of how cell death occurs in RP, a disease in which rod function (responsible for peripheral and night vision) is lost over time. This system will be used to examine the effects of rod cell death on the remaining cells of the retina, which will help us to better understand the progression of retinitis pigmentosa, and bring researchers closer to identifying therapies to benefit RP patients.
Elise Héon - Patient Registry
The Hospital for Sick Children
Registry design, construction, testing for phenotype-genotype correlation and molecular characterization, management & therapy
Granted: $250,000 over 5 years, July 2005 – June 2010
This grant was awarded to initiate a registry of patients affected by retinitis pigmentosa (RP). It will record clinical diagnostic and genetic data, while protecting the confidentiality of patients’ personal information. Thus it will provide a database for relating the clinical characteristics of RP to specific genetic mutations, thus identifying patientsfor testing new therapies as they emerge. The overall goal is for the registry to facilitate the capture and flow of information and ultimately, the safe delivery of vision-saving interventions to the appropriate candidates.
Torben Bech-Hansen
University of Calgary
Genetic and Molecular studies of CSNB in man and mouse
Granted: $270,000 over 3 years (plus $12,000 in first year for equipment), July 2007 – June 2010
Dr. Torben at the University of Calgary will focus on finding the underlying genetic causes of inherited retinal diseases, and understanding how these genetic defects disrupt the function of the retina and cause impaired vision and blindness. In particular, he will study a group of disorders called Congenital Stationary Night Blindness (CSNB). Patients with CSNB present with several of the following features: impaired visual acuity, poor night vision or night blindness, myopia (short sightedness), nystagmus (involuntary eye movement) and strabismus (misaligned eye). We have identified the genes responsible for the two common forms of CSNB (CSNB1 and CSNB2). One of these genes, CACNA1F, codes for a specific calcium channel protein that is present in photoreceptors, while the second gene produces a protein called nyctalopin, which is attached to the outside of retinal nerve cells but whose function is not known.
In ongoing studies using DNA samples from CSNB patients from various eye centres across Canada, USA and Europe, we are evaluating what other genes may cause CSNB. In another study, we generated a model of the CSNB2 condition by putting a mutation into the CACNA1F gene of the mouse. Studying the retina of this mutant mouse revealed structural and functional features suggesting that the retinal defect in patients with CSNB2 may be the failure to form proper synaptic junctions between photoreceptors and their fellow retinal nerve cells, in this way preventing the transfer of the visual signal from the photoreceptors to the visual centre of the brain. We are investigating this possibility by using novel methods of inspecting the human retina. Furthermore, we are using our mutant CACNA1F mouse to identify genes that influence the clinical severity seen among patients with CSNB2. The proteins of such modifier genes, we expect, will represent important molecular targets for treatment of CSNB.
In summary, our studies provide the basis for definitive molecular diagnosis of CSNB, the opportunity to understand the biological causes of CSNB, and for defining the clinical picture of various forms of CSNB and identifying suitable molecular targets that could led us to treatment strategies for CSNB.
Robert L. Chow
University of Victoria
Mouse models of human VSX1-associated retinal and corneal disease
Granted: $225,000 over 3 years, July 2007 – June 2010
Dr. Robert Chow at the University of Victoria is investigating whether mutations of the gene, VSX1, which are associated with human retinal circuitry dysfunction, macular degeneration and corneal dystrophies, are causing these diseases. In the research community, it is currently unresolved whether these VSX1 mutations cause eye disease because researchers don’t know what role VSX1 plays in cone photoreceptor function, macular degeneration or corneal well-being. As part of his research, Dr. Chow’s lab will study mice with mutations in their VSX1 gene which are identical to those identified in humans. Demonstrating what role these VSX1 mutations play in eye disease aids in understanding these diseases. These findings can help in the clinical diagnosis of these diseases and provide essential information for the development of treatments and cures.
Jane McGlade - Arthur and Sonia Labatt Endowment
Hospital for Sick Children
Regulation of CRB in PRC morphogenesis and survi
Granted: $270,000 over 3 years, July 2007 – June 2010
Dr. Jane McGlade at the Hospital for Sick Children in Toronto is studying how CRB1 gene mutations cause retinal degeneration, by examining how these mutations affect the structure and survival of photoreceptor cells (rods and cones in the eye that capture light). This is important because CRB1 genes are responsible for 4% of autosomal recessive RP (RP12) and 10-15% of cases of Leber congenital amaurosis. While researchers don’t fully understand the role that CRB1 plays in these diseases, previous studies have shown that the CRB1 gene maintains the proper structure of photoreceptor cells and protects them from stresses that can cause cell death. To function properly the CRB1 protein forms connections with other proteins. Dr. McGlade will study how these proteins interact with CRB1 and then determine the role of these proteins in mouse retina development and degeneration. The goal of this research is to gain clear understanding of how CRB1 mutations lead to retinal degeneration. This information will point to potential therapeutic approaches aimed at restoring CRB1 function to prevent retinal degeneration.
Ulrich Tepass
University of Toronto
Drosophila models for retinal degeneration
Granted: $270,000 over 3 years, July 2007 – June 2010
Photoreceptors (rods and cones that capture light) are important for healthy vision. But when there are mutations in the genes responsible for keeping photoreceptors healthy, it causes retinal degenerations and blindness. Dr. Ulrich Tepass at the University of Toronto is studying the formation and maintenance of retinal photoreceptor cells in fruit flies. The same molecules contribute to the formation of the retina in fruit flies and humans. This study is important because it will generate valuable information about the molecules controlling the design of photoreceptors and this could eventually open up new avenues for therapeutic strategies for the prevention or treatment of retinal degenerations (RP).
Postdoctoral Fellowships
Budd A. Tucker
Schepens Eye Research Institute Harvard Medical School
Role of MMP2 in retinal regeneration
Granted: $105,000 over 3 years, July 2008 – June 2011
Dr. Tucker will utilize tissue-engineering techniques, specifically polymers that degrade following transplantation, to deliver active MMP2 (an enzyme known to degrade proteins that block regeneration) directly to injured retina in an attempt to restore vision following retinal transplantation.
Injury caused by retinal degeneration creates an inhibitory scar, at the outer areas of the retina. This scar contains molecules such as the chondroitin sulfate proteoglycans (CSPGs) that are known to stop cellular growth and movement, thus acting as a barrier to regeneration. If successful, the removal of this inhibitory barrier, by delivering MMP2, will stimulate cellular integration and vision restoration following retinal transplantation.
Karine Zaniolo
Supervisor: Sylvain Chemtob, Ph.D.
Centre Hospitalier Universitaire Mere-Enfant
Krebs cycle intermediates: Novel mediators of retinal angliogenesis and implications in ischemic retinopathy
Granted: $105,000 over 3 years, July 2007 – June 2010
Neovascularization (formation of new blood vessels) is a major cause of retinal disease and loss of vision in people with diabetes and the wet form of age-related macular degeneration (AMD). It also plays a role in retinopathy of prematurity (ROP), which causes vision loss in prematurely born babies. Dr. Zaniolo at the Research Centre of Sainte-Justine Hospital will determine whether a novel metabolic signal, called succinate, causes neovascularization in a model of ROP. If the study finds succinate stimulates neovascularization in the eye, it might be a target for new therapies to combat ROP and other sight-threatening diseases.
The main current medical therapy to stop the growth of new blood vessels in the retina is a treatment that blocks the action of VEGF, a growth factor that stimulates blood vessel development in those with wet AMD. Because anti-VEGF therapies are expensive and require repeated injections into the eye, it is important to continue the search for cheaper and less invasive ways to inhibit neovascularization.
Graduate Student Scholarships
Robert Cantrup - Arthur J.E. Child Foundation
University of Calgary
The role of Zac1 in rod photoreceptor development
Granted: $60,000 over 3 years, July 2008 – June 2011
Rob Cantrup of the University of Calgary is focused on understanding how Zac1, a gene found in the retina, interacts with other genes and effector molecules to negatively regulate the formation of rod photoreceptors.
Evidence exists that in the absence of Zac1, extra rod photoreceptors are generated, while on the other hand, the overexpression of Zac1 decreases the number of rods generated.
Through genetic, molecular and cellular studies, Rob Cantrup will explain how Zac1 acts as a negative regulator of a rod fate. More specifically, Rob Cantrup will identify the genetic partners of Zac1 and the downstream genes that Zac1 regulates. He will also test if the inhibition of Zac1, which should increase photoreceptor production, would be therapeutically useful in a mouse model of RP.
In the long-term, this research may allow the manipulation of Zac1 (either alone or in combination with other genes) to be used as a preventative therapy used prior to the onset of photoreceptor loss in RP patients. While cell based therapies offer some promise for the replacement of lost photoreceptors in RP or AMD patients, the ability to generate even more photoreceptors via genetic manipulation is likely to further enhance the design of novel treatment regimes.
Alexa Bramall
Supervisor: Roderick McInnes, Ph.D.
Hospital for Sick Children
Endothelin-2 and Inherited Photoreceptor Degeneration
Granted: $60,000 over 3 years, July 2007 – June 2010
Retinitis pigmentosa (RP) is the most common form of inherited blindness. It causes the progressive degeneration of photoreceptors (PRs), or the light-sensing cells of the retina. There are more than 130 genes which can cause inherited photoreceptor degeneration (IPD), but little is known about how the mutated PRs die. Alexa Bramall, a graduate student working at the Hospital for Sick Children, is conducting research to explain this degenerative process. By understanding the events proceeding PR cell death, researchers can begin to develop the treatments needed to prevent or slow down the disease.
In her research, Alexa is working with a gene that has been implicated in many types of inherited photoreceptor degeneration, environmental and genetic. She has shown that the absence of this gene in mice rescues close to 50% of the photoreceptors in the retina. If this protection of PRs can be replicated in humans, e.g. by inhibiting the gene product or using compounds that block downstream signaling pathways, then this research holds much promise for the development of future therapies to treat RP and possibly other retinal disorders.
Vasanth Ramamurthy
Supervisor: Michel Cayouette, Ph.D.
Institut de recherches cliniques de Montréal
Role of numb in photoreceptor development
Granted: $60,000 over 3 years, July 2007 – June 2010
Photoreceptors (PR) are light sensing cells in the retina that play a critical role in converting light into an electrical activity that can is interpreted as images by the brain. When photoreceptors degenerate, it leads to blindness and is characteristic of diseases such as retinitis pigementosa (RP). Degeneration of photoreceptors is caused by certain mutations in genes. It is important to understand the biological processes involved in the development of photoreceptors to tackle diseases like RP.
Vasanth Ramamurthy, a PhD student at the Institut de recherches cliniques de Montréal, recently discovered a protein that appears to be involved in the development of photoreceptors. He and his team plan to investigate, in detail, the role of this protein and its function in the photoreceptor. The study could lead to the discovery of new mutations which contribute to RP and other photoreceptor degenerative diseases.
Mylene Pouliot
Supervisor: Réjean Couture, Ph.D.
Université de Montréal
Kinins involvement in vascular aspects of diabetic retinopathy in rats
Granted: $60,000 over 3 years, July 2007 – June 2010
Diabetes is the most common cause of blindness in the working-age adult population in North America. This vision loss results from damage to the retina because of blood supply failure. Circulatory failure in diabetes is due to the sustained high concentration of blood glucose and to inflammation. Inflammation results in the production of “kinins”, chemical signaling molecules that may change retinal blood flow by interacting with the receptor “B1R” on blood vessels. The main hypothesis to be tested by Mylène Pouliot (University of Montreal) is that the specific B1R-blocking drug will prevent diabetic retinopathy. Since the targeted receptor, B1R, is found only in damaged tissues, drugs directed against it would affect only those tissues that have been affected by diabetes. This study will also help researchers to understand better how blood flow is regulated in the eye. It might also lead to better therapies for any retinal disease in which inflammation-derived kinins and blood vessel problems are involved, such as uveitis and even AMD.