Solving the Puzzle

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New tool could provide insights to make cell therapy an effective treatment for vision loss.
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The assay developed by Dr. Wallace’s team could help researchers piece together the factors that have limited the use of cell-based treatments for vision loss.

A team of researchers at the University Health Network has developed a novel research tool that could help to advance new treatments to reverse vision loss caused by age-related macular degeneration (AMD).

AMD is a leading cause of vision loss in older adults. It is characterized by the loss and/or dysfunction of the cells that initiate vision. These cells—known as photoreceptors—detect light, transform it into electrical signals that are then relayed through nerve cells to the brain, where the signals are translated into images.
 
Researchers are currently exploring cell replacement therapy as a potential treatment for AMD. Cell replacement therapy involves the surgical transplantation of healthy photoreceptors from a donor into a host, replacing the lost or dysfunctional photoreceptors.
 
“Once transplanted, donor photoreceptors need to mature and establish functional connections to the host cells to be able to dispatch electrical signals to the brain. Presently, it appears that transplanted cells are not making these important connections, and we don’t know why,” says Dr. Valerie Wallace, a Senior Scientist at the Krembil Research Institute.
 
To address this, Dr. Wallace and her research team developed an efficient and inexpensive assay to identify and study the mechanisms that control the maturation of donor photoreceptors.
 
Using this assay, the researchers showed that the following three factors influence the initial stages of connectivity: the ROCK protein, which controls the growth of eye cells; Müller glia, which are cells that provide structural and functional support to nerve cells; and the CRX gene, which is important for the development of photoreceptors.
 
“We have established a novel assay to help us understand the mechanisms that regulate connections between donor and host cells. Our assay could reveal factors to promote these connections, which are crucial for cell replacement therapy to successfully restore vision in patients with AMD and other diseases that cause photoreceptor degeneration,” concludes Dr. Wallace.
 
This work was supported by Brain Canada, the Foundation Fighting Blindness, the Ontario Institute for Regenerative Medicine, the Krembil Foundation, the Canada First Research Excellence Fund and the Toronto General & Western Hospital Foundation. MS Shoichet is a Tier I Canada Research Chair in Tissue Engineering.
 
Tsai ELS, Ortin-Martinez A, Gurdita A, Comanita L, Yan N, Smiley S, Delplace V, Shoichet MS, Nickerson PEB, Wallace VA. Modeling of Photoreceptor Donor-Host Interaction Following Transplantation Reveals a Role for Crx, Müller Glia, and Rho/ROCK Signaling in Neurite Outgrowth. Stem Cells. 2019 Feb 4. doi:10.1002/stem.2985.

 

Dr. Valerie Wallace, Senior Scientist, Krembil Research Institute. Photo courtesy of the Globe and Mail.