Injection that could improve fading sight in ageing eyes starts human trials after curing blindness in mice
By Jonathan Chadwick
Daily Mail
October 22, 2020
Scientists have used gene therapy to restore sight in blind mice and plan to start clinical trials of the technique on humans later this year.
Key to the process is a light sensing protein called MCO1 opsin, which restores vision when attached to specific cells at the back of the eye.
These so-called bipolar cells, which remain intact in people with common eye diseases, are part of the sensory pathways for light perception and vision.
In trials by the US firm Nanoscope, totally blind mice with no light perception were shown to regain significant retinal function and vision after treatment.
Treated mice were faster in visual tests in the lab, such as navigating mazes and detecting changes in motion.
In humans, the therapy would be administered as a single injection into the eye for elderly people with age-related macular degeneration and retinitis pigmentosa (RP).
'A clinical study in people will help us understand how signalling through bipolar cells affects vision quality,' said study author Subrata Batabyal at Texas-based firm Nanoscope.
'For example, how well treated eyes can pick out fast-moving objects.'
The researchers found no concerning safety issues in treated mice and examination of blood and tissues found no signs of inflammation due to treatment.
Under a best-case scenario, the therapy could help patients achieve 20/60 vision, meaning they'll be be at 20 feet to see what a person with normal vision can see at 60 feet.
However, the team aren't certain how the restored vision will compare to normal vision of a person with healthy eyes.
'If this optogenetic approach using cells spared in degenerated retina can prove to be effective in vision restoration in humans, beyond light perception, it could offer a valuable alternative to the retinal prosthesis approach for people with late-stage retinitis pigmentosa,' said PaekGyu Lee at the National Institutes of Health, which funded the project.
A variety of common eye diseases including age-related macular degeneration and RP damage the photoreceptors – the cells in the retina that respond to light – which impairs vision.
But while the photoreceptors may no longer fully function, other retinal neurons, including a class of cells called bipolar cells, remain intact.
The investigators identified a way for bipolar cells to take on some of the work of damaged photoreceptors.
The first part of the procedure involves a harmless virus being modified to contain a human gene.
That virus is then injected into the eye and travels to the back of the eye to the cells in the retina.
The human gene is the virus then causes retina cells to produce a light-sensing protein called MCO1 opsin.
MCO1 opsin restores vision when attached to retina bipolar cells by allowing bipolar cells to take on some of the work of damaged photoreceptors.
'Bipolar cells are downstream from the photoreceptors, so when the MCO1 opsin gene is added to bipolar cells in a retina with non-functioning photoreceptors, light sensitivity is restored,' said Samarendra Mohanty at Nanoscope.
Opsins are the universal photoreceptor molecules of all visual systems in the animal kingdom.
They can change from a resting state to a signalling state upon light absorption, resulting in a signalling cascade that produces physiological responses.
In a normal eye, opsins are expressed by the rod and cone photoreceptors in the retina.
When activated by light, the photoreceptors pulse and send a signal through other retinal neurons, the optic nerve, and on to neurons in the brain.
Other opsin replacement therapies require the intensification of light in order to reach the threshold required for cells to process light, but intense light risks further damage to the retina.
Nanoscope's therapy requires a one-time injection into the eye, no hardware and no invasive surgery, unlike the bionic eye implants such as Argus II.
Argus II combines a miniature eye implant with a patient-worn camera and a small portable processing unit to help people see.
Therapy with the MCO1 opsin could also treat a wider range of degenerative retinal diseases, where photoreceptors no longer fully function.
The study has been published in Nature Gene Therapy.
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