An article i found related to recent progress for a glaucoma treatment

Chemical cocktail could restore sight by regenerating optic nerves

The optic nerve has been partly regenerated in mice, raising hopes for treating blindness caused by conditions such as glaucoma

By Michael Le Page

16 February 2024

Glaucoma occurs when the optic nerve, which connects the eye to the brain, becomes damaged

Ian Miles / Alamy

The vision of mice with damaged optic nerves has been partly restored by generating new nerve cells in the eye to replace ones that died. The hope is this approach could help treat people with conditions that cause blindness by damaging the optic nerve, such as glaucoma.

“We can regenerate those cells,” says Biraj Mahato at the Children’s Hospital Los Angeles in California. But more studies in larger animals will have to be done before trials in people can be considered, he says.

Glaucoma is one of the most common causes of blindness worldwide. There are several forms, but all damage the optic nerve that carries information from the eyes to the brain. The progress of the condition can be halted once diagnosed, but often it is detected only after there is a significant loss of sight. At present, there is no way to restore lost vision.

Various teams around the world are working on ways to replace the nerve cells in the optic nerve, called retinal ganglion cells, that die as a result of glaucoma. The main bodies of retinal ganglion cells are found in the retina, but they have long projections, called axons, that must extend all the way to the brain.

One idea for restoring vision lost because of glaucoma is to generate new retinal ganglion cells from stem cells in a lab and transplant them into the eye. But even if it works, this kind of cell therapy will be extremely expensive because of the difficulties of growing cells outside the body.

Mahato and his colleagues are instead coaxing existing cells within the eye to turn into nerve cells. They have developed a cocktail of eight chemicals that induce support cells known as Müller glia to turn into what appear to be retinal ganglion cells.

When his team tested the cocktail in mice whose optic nerves had been chemically damaged, the researchers saw signs of vision recovery starting two weeks afterwards and continuing for at least four months.

One test involved mice walking across a transparent surface with an apparent drop underneath one side, known as the visual cliff experiment. Almost all the non-glaucoma mice chose to walk on the side with no visual drop, but this preference didn’t occur in those with damaged optic nerves. However, 45 days after treatment, 72 per cent of the treated mice chose the side with no drop.

The researchers did a number of other studies to confirm that the new retinal ganglion-like cells had developed from Müller glia and that they were extending axons towards the brain. They also showed that when human Müller glia growing in a dish were treated with the cocktail, they turned into retinal ganglion-like cells.

Mahato thinks this approach has a number of advantages over growing cells for transplantation. It is very quick and means there are no issues with immune rejection, he says.

Another reason why turning existing cells in the retina into new nerve cells could work better than transplanting cells is because retinal ganglion cells need to be integrated into the retina, says Ted Garway-Heath at the UCL Institute of Ophthalmology in the UK, who studies glaucoma. “It is an approach worth pursuing, but Dr Mahato is absolutely right that there is much to be done before human trials,” he says.

There are several reasons why the treatment might not work in people, says Garway-Heath. One is that their axons have to grow a lot further to reach the brain than those in mice do. Another is that the structure through which axons leave the eye is damaged in glaucoma and might block the growth of new axons.

Assuming the treatment does work, it could help many people. It is estimated that 6 million people in the US alone have glaucoma, says Mahato. “And half of them even don’t know they have it.” Globally, 80 million people are affected, he says, with the number projected to rise to 110 million by 2040.

In addition to glaucoma, Mahato plans to test whether the approach could help treat a rarer condition called optic nerve hypoplasia in which the optic nerve fails to develop properly, which can lead to blindness in young children. It is also possible that it could help people whose optic nerve has been physically damaged, says Mahato, but his team is focusing on glaucoma and optic nerve hyperplasia.