Apr 3, 2023

Re-activating light sensing circuits in the retina to restore sight

This month we wanted to share more about an exciting optogenetic project that Fighting Blindness Canada is funding.

In 2022, Dr. Julie Lefebvre (Sick Children’s Hospital) and Dr. Arjun Krishnaswamy (McGill University) were awarded a research grant to study how inner retinal cells transmit light signals after retinal degeneration has occurred.

Dr. Julie Lefebvre
(Sick Children’s Hospital)

Dr. Arjun Krishnaswamy
(McGill University)

How retinal cells sense and send light signals

A leading cause of blindness in retinal degenerative diseases is the loss of photoreceptor cells. Photoreceptor cells detect light and start a signal that is transmitted through the retina and then to the brain, where it is interpreted to form images. Photoreceptors are just one of the many cell types that make up the retina. All of these cells work together to transmit light signals and produce vision. When photoreceptor cells die in diseases like inherited retinal diseases or age-related macular degeneration, the majority of the other retinal cells (also called inner retinal cells) survive. However, it is not clear if these inner retinal cells maintain their cell-to-cell connections and are still able to process and send light information.

Using optogenetics to study cell circuits and light transmission

Optogenetics is a technique that is being studied as sight-restoring therapy. In optogenetic therapy, inner retinal cells are altered so that they can sense light. The goal is that these altered inner retinal cells can replace the function of lost photoreceptor cells which are normally the light sensors in the retina. Early optogenetic therapies have shown some promise. However, they don’t restore vision as we know it, but instead can produce light signals (e.g. flashing lights) which individuals learn to interpret as objects or for mobility.

Dr. Lefebvre and Dr. Krishnaswamy are collaborating on a research project that combines optogenetic and circuit mapping approaches with the aim to ultimately develop better optogenetic therapies. They are studying if inner retinal cell connections are disrupted after photoreceptor cells are lost. They will also test how inner retinal cells can be “reactivated” to transmit visual information in a way that the brain can form functional images. As Dr. Lefebvre explains, “We are excited to combine our optical- and molecular-genetic tools to map retinal circuits in blindness models, and to learn how their wiring patterns might be harnessed for vision restoration.”

In the first year of their project, Dr. Lefebvre and Dr. Kirshnaswamy’s teams have begun their studies with a focus on retinal circuits that detect motion. Using an animal model of retinitis pigmentosa, they have determined that even after photoreceptors cells have been lost, many of the inner retinal cells that detect motion are still in place. The next step will be to determine if these cells can detect motion in a similar way as cells in a healthy retina.

The results of this study could have a big impact on the field of optogenetic therapy. It will also contribute to the successful development of other sight restoring therapies including stem cell therapy and retinal prostheses.