Clues to treatment from the developing retina
When AHFMR Senior Scholar Dr. Sarah McFarlane was considering joining the University of Calgary, one of the things that impressed her most was the fact that senior researchers in neuroscience were still involved with laboratory work. She saw a dynamic group of scientists who were intent on adding new researchers and pushing research into new areas.
Fast-forward ten years. Dr. McFarlane's instincts were on target. The University of Calgary has established itself as a leader in neuroscience: it is home to the Hotchkiss Brain Institute as well as numerous neuroscience-related research groups. Dr. McFarlane helped set up one of these—the Genes and Development Research Group—and now chairs it. Members examine genes that regulate developmental processes in all multicellular animals, from worms to humans.
One of Dr. McFarlane's research themes is the development of neurons (nerve cells) in the eye. While this is basic research, it has important links to human health because a number of diseases damage the optic nerve, which carries visual information from the eye to the brain. These include glaucoma; metabolic disorders such as diabetes, kidney failure, and thyroid disease; and fetal alcohol spectrum disorder. Diminished blood supply, with associated reduction in oxygen, to the optic nerve shortly before or after birth can also cause damage.
One potential strategy for fixing this damage could be to place stem cells into the adult nervous system and direct them to develop into ganglion cells in the retina (the light-sensitive tissue in the back of the eye). As they begin to grow, the ganglia develop filaments called axons, which then grow toward the visual centre of the brain.
Because none of this can be done currently, the big question is: How can you make it happen? As Dr. McFarlane notes, "We already have the answer: in the embryo. So if you could figure out how the retina develops in the embryo, it would give you clues about how to fix things in adults. That's what developmental neurobiologists like myself do. We try to figure out the molecules and mechanisms behind development. It's possible that what we reveal in our experiments will be the basis of future therapies."
Recently, Dr. McFarlane has been studying the process by which axons find their way to the appropriate destination—in the case of the retinal ganglion cells, the visual processing centre of the brain. How do they know how to get there? These axons have a structure at their growing tip called the growth cone, which interprets the chemical signals from molecules sent out by the message centre at their destination. Dr. McFarlane's lab has identified a number of the molecules that give out such signals.
"It's an enormous task to grow from the eye to the brain," says Dr. McFarlane. "We suspect that axons grow to a series of intermediate targets, where molecules tell them what to do, then go to the next intermediate target. We think that fibroblast growth factors, a family of proteins involved in development, control the chemical signals that tell axons to move on once they have arrived at an intermediate target. We're testing this idea now.
"The model system I work in is the frog. Its visual system develops in just three days, which makes it ideal. In the long term, I'd like to see the results from my work applied to mammalian systems, and eventually to people. But as a researcher, you can't do it all. Collaboration is key."