Profile: Astrid Limb
The Institute of Ophthalmology’s Astrid Limb plans to retire once she’s used stem cells to restore the sight of a glaucoma patient. And she’s not far off, judging by the research she described to Sarah Harrop in her profile taken from our Annual Review 2011/12.
Professor Astrid Limb partly owes her choice of research to a mistake made by a lab technician in 2002. At the time, Astrid’s lab was growing cultures of nerve cells from eyes and brains. But some of the cell culture flasks were mislabelled by the technician and a flask of nerve cells taken from the eye was grown under the wrong conditions.
“When we came to study the cells later, we found that there was one cell line that seemed to be immortal,” explains Astrid. “Then the technician went on holiday and left behind cultures of human eye cells. We discovered that a similar population of human cells, grown under the same conditions, were also becoming immortal.”
Astrid noticed that, under certain growth conditions, these cells acquired features of different nerve cells in the retina. She’d made a striking discovery: that there was a population of stem cells in the adult human eye which was able to generate many different types of nerve cell.
Fast forward 10 years and stem cell research is a burgeoning field. Today Astrid leads research at the Institute of Ophthalmology in London which focuses on using the adult retinal stem cells she discovered, known as Müller glial stem cells, to regenerate the retina in vision disorders such as glaucoma.
Glaucoma is a leading cause of irreversible blindness, with 70 million sufferers worldwide. It occurs when a build up of pressure in the eye leads to the death of retinal ganglion cells (RGCs), which form the fibres of the optic nerve, and which transmit visual information from eye to brain. The condition can be treated in the early stages, but if diagnosis comes too late or if treatment doesn’t work, damage to the eye cannot be reversed.
“Once people with glaucoma go blind there is no cure. So our hope is that we might be able to replace some of the nerve cells in the eye using stem cells,” Astrid says.
In 2012, with funding from the MRC, Astrid’s group reported they’d successfully used Müller glial stem cells to repair nerve cells damaged in glaucoma, partially restoring vision in rats which had previously been blind.
They used chemicals to induce Müller glial stem cells to grow into precursors of RGCs, before transplanting them onto the retinas of rats which had damage to their own RGCs. After four weeks, the injected cells appeared to have formed new connections (synapses) with existing nerve cells and the rats had significantly improved retinal function when their vision was tested under very low light conditions.
This technique might lead to a new way of slowing or even reversing the deterioration of sight in glaucoma and other degenerative vision conditions if it can be applied in people.
But human eyes are different to rats’ eyes because they have proportionately smaller lenses and also more liquid inside the eyeball, known as vitreous humour.
If stem cells were to be injected into the vitreous humour in humans they would disperse and fail to attach to the retina. So the research team has recently begun seeding the stem cells onto a thin membrane of protein. They then surgically remove the vitreous humour from the eye and place the membrane on the retina to allow the cells to migrate to where they are needed.
“The surgery we’re doing in animals is actually very similar to a routine operation in humans for retinal detachment, and we have a consultant ophthalmic surgeon from Moorfields Eye Hospital and an MRC clinician scientist who are helping us with this work,” explains Astrid.
Having identified the cells, how to differentiate them, and proved that they are safe to use, Astrid is hopeful that the first clinical trials to use this technique might only be five years away. Long term though, she thinks that a different approach will be needed to restore sight permanently.
“Because Muller glial stem cells are already present in the eye, I envisage that we might ultimately be able to encourage them to differentiate in the eye using drugs,” explains Astrid.
Astrid’s career ambition is to establish a stem cell therapy for glaucoma and to help a blind person to see again, and at the current rate of progress she is nearly there. She regularly speaks to glaucoma patients and says they are a source of inspiration and motivation.
“It’s a very debilitating condition, and it’s particularly upsetting to see children losing their sight from an early age and the effect that has upon them and their parents. And for adults, who have lived a normal life to suddenly lose their sight and not being able to cross the road alone or go shopping — it’s the end of their normal daily lives.
“So if, by the end of my career I could establish a stem cell therapy for glaucoma and see just one person who has lost their sight to have their vision restored, that would be a dream — and then I can happily retire!”
Download the MRC Annual Review 2011/12: Advancing medicine, changing lives, available in pdf or ebook formats.