Research

Develop Human Stem Cell Models to Understand and Treat Disorders in the Eyes and the Brain

Stem cell transplants are already being used at the Donald K. Johnson Eye Institute to restore sight to people blinded by severe cornea disease and injuries. This surgical team, led by Dr. Allan Slomovic, is the only Canadian team with the expertise to perform this procedure. In addition, Dr. Clara Chan, a Clinician Investigator at the Institute was the first doctor in Canada to perform a deceased donor ocular limbal stem cell transplant.

New therapies for retinal degeneration are focused on the next generation of regenerative medicines. These include gene and cell-based therapeutics, including stem cells. Several of these approaches are already being applied in clinical trials and therapies. While gene therapy has the potential to correct the underlying mechanism of disease in monogenic disorders, it depends on the presence of viable light-sensitive cells. Stem cell therapy has the potential to replace the light-sensitive photoreceptors lost in later-stage disease when patients have suffered significant vision loss. Cell-based therapies hold promise for both IRDs and acquired conditions, and discovery in this area is the central aim of Dr. Brian Ballios' Lab at the Donald K. Johnson Eye Institute.

Protect Cells Threatened by Degenerative Disease

No cell grows and acts in isolation. The cells of the human eye communicate through an extensive series of chemical signals. Even the process of cell death is regulated by these signals. Scientists at the Donald K. Johnson Eye Institute are working to document these communications in healthy and diseased eyes, and to develop drug therapies that interrupt processes leading to cell death. Such therapies may not reverse blindness, but they do have the potential to slow vision loss in its earliest stages.

Research to protect vision cells at the Donald K. Johnson Eye Institute primarily focuses on understanding cell signals involved in glaucoma and retinitis pigmentosa and in developing therapies for these conditions.

Damaged ganglion cells in the retina, connecting the eye to the brain, can be protected by providing survival nutrients. However, this is a challenging procedure as these molecules need to be administered locally in the retina and made available for the ganglion cells. Previous work from

Dr. Michael Reber showed that such nutrients can be trapped in reconstituted silk fibers. With the recent progress of 3D printing technology, generating bio-active silk fibers containing survival nutrients has been made easier and more reliable. Dr. Reber is now able to print these fibers in an automated manner and test the effect of different blends of molecules on the survival of retinal neurons. The objective is to identify the optimal mixture of molecules that maximizes the survival and regrowth of ganglion cells in the retina. His approach will lead to more efficient therapies for glaucoma and optic neuropathies.

Studying cell communications and targeting these messages with specially designed molecules has become an important strategy for modern drug development. For example, the development of drugs that target cell communications around blood vessel growth has revolutionized the treatment of wet age-related macular degeneration. Institute clinicians have been heavily involved in clinical trials testing wet AMD therapies and will be clinical partners in future drug testing.

Regenerate Damaged Cells and Tissues to Restore Sight

Today there is the promise that the natural process of cell development could be harnessed to grow new cells for a damaged eye. At the Donald K. Johnson Eye Institute, stem cells and other immature cell types are being used to create new eye cells in the laboratory, and the genetic and chemical control of this growth process is being studied in minute detail. Transplants of these cells may finally offer treatments for currently irreversible blindness associated with age-related macular degeneration and glaucoma.

Stem cell transplants are already being used at the Donald K. Johnson Eye Institute to restore sight to people blinded by severe cornea disease and injuries. This surgical team, led by Dr. Allan Slomovic, is the only Canadian team with the expertise to perform this procedure.

Mechanisms of Eye-Brain Connectivity

Cells communicate through chemical signals received by specific receptors on the surface of the cell. Dr. Philippe Monnier examines a particular combination of signal and receptor, known as the RGMa and Neogenin. Dr. Monnier has shown that blocking the interactions between the two can help prevent cell death in retinal eye diseases, and in other neurological conditions such as multiple sclerosis and stroke, when studied in the laboratory. It can also be used to promote the growth and connection of new cells. Dr. Monnier continues to work to understand how best to develop this potential therapy, either by modifying the receptor or by targeting the signal.

Vision Rehabilitation

The human eye captures light and stimuli, but ultimately it is the brain that "sees" – interpreting electrical signals and directing the movement of the eyes. Healthy vision relies on communication between the eyes and the brain. Disruptions in the small unconscious movements of the eyes can be an early indicator of vision loss; it is frequently used to help diagnose eye disease before a child can speak. New scientific research is suggesting that eye movement may also help evaluate brain disorders such as Alzheimer's.

Due to the adaptability (plasticity) of the human brain, it is possible to re-train the brain to overcome abnormal eye movements or to maximize limited vision associated with eye disease. This is key to visual rehabilitation. Scientists at the Donald K. Johnson Eye Institute are studying the changes that occur in the brain when abnormal eye movements occur, in order to better understand when and how rehabilitation should be done.

Dr. Michael Reber, Senior Scientist at the Donald K. Johnson Eye Institute, along with Dr. Monica Nido and Dr. Samuel Markowitz from the Low Vision Rehabilitation Clinic, is establishing a visual rehabilitation program for low-vision patients based on cognitive training and virtual reality. The objective is to stimulate the healthy part of the retina and corresponding regions in the brain to compensate for vision loss. This will rejuvenate visual perception restoring some daily life activities. Dr. Reber believes appropriate and patient-specific perceptual training using virtual reality will allow them to go around every day with more confidence and more safely, take public transportation, navigate busy streets/city more efficiently and even prolong driving. Dr. Reber and his team develop such perceptual training using portable virtual-reality headsets, remotely controlled, that can be used at home by the patients. All this will help to improve the patient's quality of life, increase their self-dependency and therefore reduce depressive symptoms.

Low vision specialists and other rehabilitation professionals with the Donald K. Johnson Eye institute frequently collaborate with our scientists to improve rehabilitation care practices.

New Treatments and Surgical Approaches

The Donald K. Johnson Eye Institute is a Canadian leader in testing new treatments and surgeries for serious eye disease. Multiple trials take place at the Institute each year, evaluating drugs and pioneering new surgical techniques.

Retinal surgeons like Dr. Robert Devenyi, Dr. Efrem Mandelcorn and Dr. Mark Mandelcorn have evaluated new surgical approaches to treating detached retinas, the use of drug implants to combat serious eye infections, and the utility of emerging diagnostic tools. In addition, Dr. Efrem Mandelcron and his team are also investigating the usage of the human amniotic membrane (hAM) as a vision-saving option for patients with large macular holes in the eyes.

Dr. Allan Slomovic led the implementation of another innovative surgery, stem cell transplants to restore sight to people blinded by severe cornea disease and injuries. This is the only Canadian team with the expertise to perform this procedure. Dr. Clara Chan and Dr. David Rootman were the first doctors in Canada to use EverPatch for tube exposure in Canada.

Other medical members of the team at the Donald K. Johnson Eye Institute, such as Dr. Michael Brent, have been part of evaluating the medications for wet age-related macular degeneration that have transformed the care of this condition, preventing serious vision loss for many seniors. In addition, Dr. Brent co-leads a Diabetic Retinopathy Screening Program with mobile imaging equipment, known as Project OPEN, helping to improve eye care and increase screening rates for vulnerable populations across Ontario. Clinics are in place across the province, in marginalized communities, to perform outreach and arrange screenings for residents.

This strategic and pragmatic approach to improving vision care at Toronto Western and across Ontario makes the clinicians of the Donald K. Johnson Eye Institute ideal partners for the Institute's translational science agenda. Together we will build on this legacy of care innovation, combining clinical experience with new biological insights to create, test and implement revolutionary new therapies for blinding retinal disease.