Fighting Blindness: UTM Researcher Studies Rare Genetic Vision Disorder

How do you know an apple...is an apple?

If you’re looking at the object, you might notice its colour, bright red or green. You’d also see the edges of it, which are required to form a shape. Once you combine the visual features of the object — the colour, shape, texture, and size — you’d quickly ascribe meaning to what you’re seeing.

This is a readily edible fruit which provides nourishment.

Now, of course you can also smell the apple, or hold the apple, or bite into the apple to taste it. But did you know that of all the sensory systems, the brain structure that deals with processing visual information occupies the biggest area? 

From foraging for food to navigation to avoiding danger, vision plays an essential role in humans and other vertebrates. 

Baohua Liu, an assistant professor in the Department of Biology, works to understand the operation of the visual system, how the brain analyzes visual information to generate an internal presentation of the external world. This information enables us to make decisions based on what we see — such as running from a tiger or toward a slice of pie. 

“Our lab also looks at how our visual perception affects our cognitive function, like emotion,” Liu explains. “If we see something to eat, we feel differently than we do if we see a predator. Why do we like some pictures, but hate others? What we see, the information it provides and the way we interpret that, all affects how we feel about it.”

Liu always wanted to be a scientist. He studied physics in college and went on to biophysics in graduate school before he turned to neuroscience, ever curious about nature and wanting to understand the human aspect of things we can see with our eyes.

He says that our brain is supported by millions of neurons and trillions of synaptic connections, which all work together to share and process information. In the Liu Lab, they’re working to understand the different type of neurons that form this synaptic connectivity, as well how they share information so that, collectively, the neurons can extract meaning from it.

In other words, our ability to understand that colour + shape + meaning = eat the apple relies on the function of this circuit.

Using an impressive combination of circuit tracing, electrophile recording, calcium imaging, behavioural testing, and computational tools — all which Liu learned traveling his windy path toward systems neuroscience — Liu and his team are able to generate a bigger picture of how the brain circuit processes information and how that leads to appropriate motor action. 

These days, he wants to use his knowledge and skills to help people. 

Soon after coming to the University of Toronto Mississauga as an independent researcher, Liu started looking for opportunities to work on a disease-related project. A former colleague, Jeannie Chen, from the University of Southern California reached out. 

Now, they’re testing a genetic rescue strategy for congenital stationary night blindness type 2A (CSNB2A), a rare and inherited eye condition that causes night blindness as well as trouble seeing during the day. 

Here’s how it works: A ‘photoreceptor’ is a cell, located at our retina, which sees and detects light. It converts that light into a neural signal. At the end of this photoreceptor — called the synaptic terminal — are L-type calcium channels Cav1.4, which mediate the transmission of the neural signals into the next step of the visual system called a ‘bipolar cell’. 

Patients suffering from CSNB2A, however, have a gene mutation in these calcium channels. Because of this mutation, the photoreceptor is unable to successfully transmit visual information to the bipolar cell — which means that the retina can’t relay that information any further to the brain to support vision. 

The disease affects a small part of the population, but those who have it suffer badly with their vision, and, so far, there is no treatment. But the recent advances in gene editing techniques have inspired Liu and others to explore genetic rescue as the therapy to cure CSNB2A.

For this purpose, Chen has developed a model of CSNB2A in which the expression of Cav1.4 is prevented genetically, leading to the phenotypes mimicking CSNB2A; however, this ‘expression brake’ can be removed by genetic treatment.

“This tool enables us to restore Cav1.4 expression at specific time points during the life cycle.” Liu says. “From there, we’ll employ state-of-the-art techniques to assess whether and how visual functions recover, evaluating both the extent and speed of recovery.” 

With the support of university funding, they have produced exciting preliminary data showing evidence that gene therapy can theoretically rescue the functions of the visual system. Next, they plan to further validate the effectiveness of gene therapy and investigate the underlying molecular, synaptic, and circuit mechanisms. 

But as Liu points out, that requires money, and it’s tough for an early career researcher with little experience in disease-oriented projects to get funding from a federal agency. 

Enter Fighting Blindness Canada (FBC), a private funding organization that’s committed to putting resources into scientists who are working on promising projects in vision research. They know that a risky project can translate into new knowledge — and that knowledge can be applied to designing novel treatments for disease.

Previous grant recipients have gone on to become prominent world-renowned vision researchers who have made ground-breaking discoveries. 

This past fall, the FBC announced the recipients of their 2024 Research Grant competition. The grants provide critical seed funding for Canadian vision researchers who need to move projects forward and to generate data that will allow them to apply for larger grants in the future. The 2024 competition focused on supporting early career researchers, and Liu was one of four awardees. 

“The money is critical for me to continue this work,” says Liu. “It enables me to get supplies and hire qualified graduate students and postdoctoral fellows to carry out the planned experiments.”

“We’ll carry out the research at different levels, from genetic, molecular, physiology, circuit, all the way to behaviour,” he says. “We hope to understand what causes the disease and how much recovery we can see by reintroducing the gene. This will give us more confidence in how likely gene therapy will be able to effectively cure the disease in human patients.” 

Calling all students: If you’re interested in neuroscience, the Liu Lab wants to hear from you! Prof. Liu’s program relies on state-of-the-art multidisciplinary approaches and tools — everything from viral-based tracing to electrophile recording, functional imaging, behavioral assays, and more. 

The Liu Lab welcomes students from various educational backgrounds, including physics, biology, chemistry, electrical engineering, and computer science. A diverse lab means students can share their skills and expertise with each other, which makes our work stronger! 

Contact Professor Liu for more information.