Home U.S Scientists use light-sensing protein to restore vision

Scientists use light-sensing protein to restore vision


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). 

Nanoscope's therapy requires a one-time injection of a modified virus into the eye. This causes retina cells to produce a light-sensing protein (MCO1 opsin), which restores vision when attached to bipolar cells at the back of the eye

Nanoscope’s therapy requires a one-time injection of a modified virus into the eye. This causes retina cells to produce a light-sensing protein (MCO1 opsin), which restores vision when attached to bipolar cells at the back of the eye

Nanoscope researchers Samarendra Mohanty and Subrata Batabyal. The firm's newly developed light-sensing protein restores vision in blind mice when attached to retina bipolar

Nanoscope researchers Samarendra Mohanty and Subrata Batabyal. The firm’s newly developed light-sensing protein restores vision in blind mice when attached to retina bipolar

WHAT IS RETINITIS PIGMENTOSA? 

Retinitis pigmentosa (RP) is a group of rare, genetic disorders that involve a breakdown and loss of cells in the retina – the light sensitive tissue that lines the back of the eye. 

Common symptoms include difficulty seeing at night and a loss of side (peripheral) vision. 

RP is an inherited disorder that results from harmful changes in any one of more than 50 genes.

These genes carry the instructions for making proteins that are needed in cells within the retina, called photoreceptors. 

Symptoms include trouble seeing at night and decreased peripheral vision. 

Source: National Eye Institute 

‘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. 

A variety of common eye diseases, including age-related macular degeneration and retinitis pigmentosa, damage the photoreceptors, impairing vision

A variety of common eye diseases, including age-related macular degeneration and retinitis pigmentosa, damage the photoreceptors, impairing vision 

WHAT ARE BIPOLAR CELLS? 

In the retina, bipolar cells exist between photoreceptors and ganglion cells. 

They transmit signals from the photoreceptors to the ganglion cells. 

Bipolar cells are the only nerve cells that connect the outer retina to the inner retina. 

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. 

Detail shows structure of retina, including location of a bipolar cell expressing Nanoscope's MCO1 opsin

Detail shows structure of retina, including location of a bipolar cell expressing Nanoscope’s MCO1 opsin

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.  

WHAT IS AGE-RELATED MACULAR DEGENERATION?

Age-related macular degeneration (AMD) is a common condition that affects the middle part of your vision. 

It usually first affects people in their 50s and 60s.

It can blur the sharp, central vision you need for activities like reading and driving, although it doesn’t cause total blindness. 

But it can make everyday activities difficult.

Without treatment, vision may get worse. 

This can happen gradually over several years (‘dry AMD’), or quickly over a few weeks or months (‘wet AMD’).

The exact cause is unknown. It’s been linked to smoking, high blood pressure, being overweight and having a family history of AMD.

Research shows that you may be able to lower your risk of AMD (or slow its progression) by making these healthy choices:

– Quit smoking — or don’t start

– Get regular physical activity

– Maintain a healthy blood pressure and cholesterol levels

– Eat healthy foods, including leafy green vegetables and fish

Source: NHS/National Eye Institute

 

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