In the first of this series, we will focus on an innovative gene therapy known as ‘optical genetics’ or ‘optogenetics’
Light-sensitive rod and cone photoreceptor cells are essential for vision because of their ability to convert light into visual information. Another type of retinal nerve cell called ganglion cells then collects this information and fine tunes it before it is sent to the brain where it is interpreted as vision.
The loss of rod and cone photoreceptors is at the root of many sight loss conditions including inherited retinal degenerations (IRD) such as retinitis pigmentosa (RP) or more common conditions like age-related macular degeneration (AMD). Many research teams around the world are now exploring ways in which they can replace, support or bypass these damaged photoreceptors.
By taking advantage of nature’s ability to respond to light, optogenetics is an exciting and innovative technique that has the potential to stimulate an alternative route to vision in the absence of working rod and cone photoreceptors.
How does optogenetics work?
Algae found in ponds and lakes contain light sensitive proteins called rhodopsins. These rhodopsins become active when exposed to light. For example, when a nerve cell containing rhodopsin is exposed to a certain colour of light, the rhodopsin becomes stimulated and change shape which in turn changes the activity of the nerve cell.
In many retinal degenerations, ganglion cells survive long after the light-sensitive rods and cones are gone, making them a prime target for vision restoration. Ganglion cells in the retina are not naturally light-sensitive.
However, scientists hope that by inserting rhodopsins found in algae into ganglion cells, they can empower these retinal nerve cells to respond to light. This brings considerable potential for providing a new type of cell in the retina which can detect light and then communicate that information to the visual part of your brain. Therefore, when your eye receives light from the environment, it is anticipated that the retinal ganglion cells will be directly stimulated and send signals along your optic nerve to your brain without any input needed from other parts of your retina.
Scientists are currently working to understand how optogenetics can restore sight to individuals with retinal diseases. To date, these methods have been shown to bring back rudimentary vision in animal models. In a recent breakthrough, Prof John Flannery and his team from Berkeley University, California reported the restoration of patterned vision in an animal model of RP. Prof Flannery, a member of the Fighting Blindness Medical and Scientific Advisory Board, used a unique, genetically engineered protein that is light activated to produce complex visual signals in the visually impaired animal.
Such positive results have prompted examinations in humans and two early clinical trials are currently underway. In 2016, a Phase I/II clinical trial began in the US which will use this gene therapy approach to evaluate if optogenetics can restore sight to people living with advanced RP. Earlier this year, a second company received approval in the UK for its Phase I/II trial, testing a treatment combining the gene therapy with a visual stimulation assistive device for people with advanced RP.
The Future for Optogenetics
This will be a revolutionary and fast moving technology which will be closely examined by many to establish how safe and effective the potential treatment is. The light sensitive proteins inserted into the cells can only respond to certain coloured light in the environment and time will tell how humans will respond to this light and how it is processed in the brain. It is also important to remember that while clinical trials are happening, scientists are still working out the fundamentals. Such clinical trials are still experiments which are being evaluated cautiously.
Current clinical trials are focusing on RP, but if successful, this gene therapy may also hold potential for other conditions including age related macular degeneration (AMD) in the future.
The Research Team here at Fighting Blindness will eagerly follow these advances over time and we look forward to learning more about the effort to use optogenetics to improve the lives for people living with sight loss.