Ensuring safety of channelrhodopsin optogenetic therapies for vision restoration
- Type of funding: Fight for Sight / Laurence Misener Charitable Trust PhD Studentship
- Grant Holder: Dr Nina Milosavljevic
- Institute: University of Manchester
- Region: North West
- Start date: September 2024
- End Date: September 2027
- Priority: Treatment
- Eye Category: Inherited Eye Disease
Brief Lay background
Retinal degenerative disorders are a group of eye diseases that include age-related macular degeneration (AMD), which most commonly affects older people – as well as rare genetic conditions, such as retinitis pigmentosa (RP), which often begin in childhood.
The retina contains millions of light-sensing cells (photoreceptors), which are vital for healthy eyesight. In people with retinal degenerative disorders, these cells stop working and eventually die – causing progressive sight loss.
What problem/knowledge gap does it help address
A next-generation treatment strategy – called optogenetics – has the potential to help to reverse sight loss in people with advanced retinal degeneration. It involves using a harmless virus to deliver a gene containing the instructions for a light-sensing protein (called a photopigment) into surviving retinal cells to give them the ability to detect light and restore vision.
Although fairly new, the approach has shown promising results in laboratory experiments and early-stage clinical trials are currently underway. But these treatments use photopigments from microscopic algae – and questions remain about their long-term safety and effectiveness. Using microbial photopigments may disturb the chemical balance in cells – causing physiological stress. Over the long term, this may even cause cell death – which could reverse any improvements to a person’s vision from the treatment.
Aim of the project
- Examine the long-term consequences of microbial photopigments on cell physiology.
- Use this knowledge to define how best to adapt the treatment approach to make it safer and more effective at restoring vision.
- Test the effect of introducing microbial photopigments on the survival of cells grown in culture.
- Test the effect of introducing microbial photopigments on the survival of different cell types in the mouse retina.
- Use live cell imaging microscopy to measure chemical changes in cells and mouse retinas expressing these photopigments.
- Work on developing a safer optogenetic therapy using alternative photopigments.
Potential impact on people with sight loss
This research could ultimately lead to the development of next-generation optogenetic therapies that can help reverse sight loss for people with retinal degenerative disorders – dramatically improving their quality of life.