Ensuring safety of channelrhodopsin optogenetic therapies for vision restoration

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.

Key procedures/objectives

1. Test the effect of introducing microbial photopigments on the survival of cells grown in culture.
2. Test the effect of introducing microbial photopigments on the survival of different cell types in the mouse retina.
3. Use live cell imaging microscopy to measure chemical changes in cells and mouse retinas expressing these photopigments.
4. 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.