Allison Tran
Supervisor: Brittany Carr
Project: Can carbohydrate molecules regenerate retina cells?
"Overcoming challenges in science is exciting, and this skill can be cultivated and applied to other aspects of life as well. Each time we fail to acquire the desired results, we still learn something new in the process."
Investigating the function of polysialic acid in retinal regeneration
Müller glia help to maintain retinal structural and functional stability and are involved in retinal repair. Müller glia express sugar molecule chains called polysialic acid (polysia), which stick out into the extracellular space and interact physically with their environment. Long polysia chains regulate cell migration by physically pushing surrounding cells away from the cell that needs to move; creating more space for migration to occur.
During development, Müller glia in pre-metamorphic frogs (tadpoles) can undergo dedifferentiation in response to a retinal injury. This allows them to travel to the injury site and create new photoreceptors or other retinal cell types to replace lost cells, thus repairing the retina. Retinal regeneration is lost in post-metamorphic frogs and mammals. The role of polysia in retinal regeneration is not well documented.
We will use the tadpole model to investigate whether polysia chains are important for retinal regeneration. We hypothesize that removing polysia will impair Müller glia migration to the injury site, inhibiting retinal regeneration. One group will receive a polysia inhibiting enzyme, endoneuraminidase, or a drug that inhibits polysia elongation called 8-keto-Neu5Ac and the control group will receive no treatment.
To determine whether disruption of polysia has an effect on retinal regeneration, we will track: 1) Whether polysia has been removed by using GFP-EndoN, which is a green fluorescent tag that binds to polysia, and 2) Whether new cells are being made and are moving to the site with a dye that incorporates into newly dividing cells called EdU. We will also track any structural changes of the Müller glia using an antibody for a protein that Müller glia express called neural cell adhesion molecule (NCAM).
Results from this study will allow us to determine whether polysia plays an important role in Müller glia-mediated retinal repair during early development. Human retinas are not fully developed until our mid-to-late 20s. Thus, if we can learn more about mechanisms of retinal regeneration, we may gain insight into ways to re-activate retinal regeneration in children and young adults and restore vision lost to injury or inherited blindness.
Allison Tran was supervised by Brittany Carr and her summer studentship was funded by the Stollery Children’s Hospital Foundation. She is enrolled in the Bachelor of Science program.
