2016 Catalyst Grants

AVN's Catalyst Grants provide seed funding for studies that offer the prospect of advancing scientific understanding and or improving patient care. In the 2016 competition, four grants were awarded.

Dr. Andrew Waskiewicz

University of Alberta

Investigations of BMP3, a candidate coloboma locus

Ocular coloboma is a frequently blinding hereditary disorder that afflicts approximately 1 in 5,000 patients worldwide. It results from improper development of the embryonic eye, and represents the second leading cause of pediatric blindness. Ocular coloboma is just one of multiple human disorders resulting when two sheets of cells fail to fuse. For example, cleft lip/palate and neural tube defects such as spina bifida are similarly caused by lack of fusion between two cell layers. Our research goal is to understand the genetic causality of ocular coloboma, thought to result from variants in more than 50 genes. We have identified families of patients that have a multi-generational history of coloboma, andutilized genome sequencing to identify variants in such patients. In parallel with such efforts, we utilize animal model systems to determine the method by which such variants result in eye disease. The long term goal of the animal model studies is to provide the foundation for therapeutics, either pharmacologic or genome editing.

Dr. Michael Walter

University of Alberta

Investigation of a candidate gene for pigmentary glaucoma

Glaucoma is the most common form of blindness suffered by Canadians. While the pigmentary form of glaucoma is the most common secondary glaucoma in North America, to date, no causative gene has been found for this blinding condition in humans. We have recently conducted genetic analyses of patients and identified a candidate gene for pigmentary glaucoma. We will now test the effects of the mutations that we identified to determine, the underlying problems that causes pigmentary glaucoma. We anticipate that this information will in time be used to detect at-risk individuals (i.e. before visual loss starts), and may accelerate investigations into the best treatment and therapies for patients.

2016 Pilot Catalyst Grants

Drs. Graf and Sauve

University of Alberta

The role of neural crest derived Bmp7 for retina epithelium development and function

The concept that some cells provide support for other cells during development, is well established during embryonic development. We have found that a secreted factor (Bmp7) derived from a rare cell type in the retina (neural crest) provides critical support for the development of the retina and normal eye function. Our aim is to investigate when and how neural crest-derived Bmp7 affects retinal development. Potentially, this knowledge may lead to new approaches for managing and treating retinal degenerative disorders, such as retinitis pigmentosa or macular degeneration.

Dr. David Pilgrim

University of Alberta

Unc119 as a Cone Rod Dystrophy Candidate Gene

My laboratory has identified mutations in two genes that have subsequently been shown to affect eye development, and both have been implicated as candidates for inherited human eye diseases. Cone-rod dystrophies (CRD) are a class of inherited retinal diseases with an incidence of approximately 1/40,000 that are characterized by progressive degeneration of cones and rods, ultimately resulting in blindness. One genetic locus that has been associated with CRD in humans is the unc119 gene that our lab has been studying in detail for many years, although in a different context. We have recently shown that reducing the amount of unc119 in the early zebrafish embryo has profound effects on the development of photoreceptors. In this proposal, we will examine in detail the requirement for these factors in different aspects of eye development, and determine how often patients with CRD carry genetic mutations in this candidate gene.

2015 Catalyst Grants

AVN's Catalyst Grants provide seed funding for studies that offer the prospect of advancing scientific understanding and or improving patient care. In the October 2015 competition, two grants were awarded to researchers at the Universities of Alberta and Calgary.

Dr. Jen Hocking

University of Alberta

Potassium channel regulation of photoreceptor size

Photoreceptors are the cells of our eye that directly detect light, and are often the first retinal cells to degenerate in blindness-causing diseases. They have a unique morphology that includes an expanded distal region, the outer segment, which is packed with light-sensing proteins and is continuously regenerated by proteins and membrane created in the inner segment. Photoreceptors come in two main types: rods for low-light vision and cones for colour vision. My lab uses zebrafish, which have excellent color vision, as a model to study photoreceptor development and maintenance. We discovered that fish with disrupted early retinal patterning also have a late- onset and unique photoreceptor abnormality, in which cone outer segments are reduced in size, but rod outer segments are expanded. Through genetic screening, we found a dramatic decrease in the expression of a potassium channel gene (kcnv2), and are now examining how an altered ability of photoreceptors to respond to light may cause misregulation of photoreceptor size. Notably, mutations in the human KCNV2 gene cause the disease 'cone dystrophy with supernormal rod response', and our work will provide insights into the biological changes underlying this disease.

Drs. Sarah Childs & Sarah McFarlane

University of Calgary

The role of FoxF2 in neurovascular interactions in the developing and adult retina

The Childs and McFarlane labs are interest in understanding the development, maintenance and interactions of two distinct systems in the eye: the neurons that are important for light detection and sending signals to the brain, and the blood vessels that provide nourishment. We have identified a gene (FoxF2) expressed in blood vessels that appears critical for the health of retinal neurons. There is evidence in mice that loss of this gene leads to glaucoma, a devastating neurodegenerative disease that results in death of the cells that make the optic nerve, and the loss of sight. We have generated zebrafish that are lacking this gene, and these fish appear to lose the same nerve cells that are lost in glaucoma. We can use this experimentally simple system to understand how a gene that is expressed in eye blood vessels controls development and maintenance of nerve cells in the eye. In this proposal we will examine where the FoxF2 gene is expressed through life, what effects loss of FoxF2 has on the eye, and begin to understand how FoxF2 promotes normal eye health.