Different barriers to cell transplant success between the inherited eye conditions

New research part-funded by Fight for Sight reveals a wide range of activity by support cells in the eye after the loss of light-sensitive (‘photoreceptor’) cells. The results are an important step towards developing successful cell transplant therapy to restore sight in people with inherited eye conditions.

Dr Rachael Pearson and team at the UCL Institute of Ophthalmology and NIHR Biomedical Research Centre at Moorfields Eye Hospital have been sretudying mice with four different types of inherited eye conditions. All the disorders involve losing the photoreceptors, although the speed and pattern of loss varies between the types.

Proof that cell transplants can work

Previous research by the team gave the first evidence that cell replacement therapy can work. They were able to give some sight back to mice with a type of night blindness if the donor cells were at the right stage of development.

They found that successful transplants were possible in mice with late-stage disease, as well as in mice with early-stage disease. But they also found that success depended on which type of eye disorder the mice had. So in the current study the researchers wanted to understand what was different between the disorders that could affect transplant success.

To be successful, young donor cells first need to be transplanted into the eye and then to move into the right place in the retina (the part of the eye that contains photoreceptors) where they can mature and connect up with other cells. But activity by support cells called ‘Müller glia’ might be making the process harder.

Scar tissue in the way

When photoreceptors are lost the Müller glial cells nearby respond to the damage by changing their shape and producing molecules that make up the ‘scaffolding’ between cells in tissue such as the retina. This complex process is known as ‘gliosis’. The end result is a scar that can eventually cover the whole retina.

We don’t know exactly why this happens. It could be to help repair damage, but it often has harmful effects. One side-effect of the scar could be that it forms a barrier that prevents donor cells from moving into position and becoming connected.

Results published in the journal PLoS ONE showed that the process of gliosis happens in a surprising variety of ways depending on the particular genetic fault causing the condition. The differences included how much the Müller glial cells changed shape and produced certain molecules.

Müller glial cells also play a very important role in the healthy retina by keeping up a barrier at the outer edge of the sensory part of the retina. The researchers found that gliosis can also affect this barrier to varying degrees.

A vital step

“It’s very interesting that the Muller glial response to photoreceptor loss is so varied depending on the specific condition and that this variation is apparently unrelated to disease severity,” said Dr Pearson. “This is very promising for the future possibility of restoring sight even in the later stages of at least some inherited retinal conditions.

“However, first we need to design therapeutic strategies that can make the diseased retinal environment more favourable to cell transplantation. These results are a vital step in that process.”

This was the first research study to compare the pattern of gliosis between different inherited eye conditions over time. The team plan to extend their investigation to include changes to the retina from age-related conditions and injury.