Research hope for retinitis pigmentosa

Post date: 
Monday, 16 March 2015

Although there is currently little treatment for retinitis pigmentosa, Radhika Holmström looks at whether recent discoveries are now coming to fruition.

There is almost no treatment for retinitis pigmentosa (RP) at the moment. However, a huge number of research projects are investigating the condition and/or specific forms of it.

What is RP?

Retinitis pigmentosa is the name for a whole range of inherited conditions that affect approximately one in 3,000 to 4,000 people altogether. They are caused by different genetic mutations, all of which affect the rod and cone cells that make up the retinal photoreceptors; the faulty genes pass incorrect messages to the body’s chemistry and the retinal layer that captures the light image breaks away.
RP is diagnosed by examining the retina to find the characteristic dark patches of pigmentation that form when the pigmented “retinal pigment epithelial” cells (from the layer of the retina that supports the rods and cones) migrate. Most cases are identified before the age of 30 (usually with difficulties with night vision and/or peripheral vision) and progress fairly slowly. 
“Whatever the underlying gene defect, the net result is that patients lose the ability to see because the light sensitive cells are progressively dying,” says Professor John Marshall, Professor Emeritus of Ophthalmology at King’s College London and Honorary Professor of Optometry and Visual Science at Cardiff University. Yet at the same time, explains David Head, Chief Executive of the charity RP Fighting Blindness, people do not “look” blind in the conventional sense, so other people may not believe that they have a sight problem. “The rest of the eye is entirely functional.”  

How gene therapy works

“There are around 100 genes that can be altered for different forms of retinal degeneration,” says Professor Alan Wright of the University of Edinburgh, who identified the first RP gene nearly 30 years ago. Increasingly, researchers are looking at rectifying that alteration.
One is to inject a healthy copy of the faulty gene with the aim of correcting it right at the level of its DNA. This, for instance, is the approach that researchers at University College London are exploring, and which has already restored some sight to patients with one form of RP. Another project at the University of California Berkeley, which published its results in December 2014, is looking at creating “replacement” photoreceptors by inserting a gene into other retinal cells. 
Dr Maria Moosajee at UCL is exploring a slightly different option: a drug that can suppress mutations, notably the “nonsense” mutations that are responsible for a number of genetic eye conditions. “It acts specifically on nonsense mutations in a disease and gene independent manner,” she explains. In other words, it can be used to treat patients with different conditions, because it is targeting the mutation itself. 

Breakthrough in stem cells

Many specialists suspect the breakthrough will come in the use of stem cells to “grow” correctly functioning photoreceptors, and there have been some huge advances in the past decade, building on the UCL discovery that there is an optimal stage in the stem cells’ development that allows a stem cell to develop into a fully mature and functional photoreceptor cell.
For instance, a team at Newcastle University is working on inducing “pluripotency” in cells (effectively resetting them to stem cell level) and then directing them to become either retinal pigment epithelial cells or photoreceptor cells, which could potentially be transplanted. However, photoreceptor cells are particularly difficult to culture, says researcher David Steel. “Becoming epithelial cells seems almost a default pathway, whereas we have to use chemical ‘cues’ for photoreceptors – and it’s also harder to identify them earlier on, because there aren’t established markers like pigment. We’re also looking at making the production of the cells more efficient. Rather than taking cells from mice at different stages of development, we’re trying to produce those cells independently.’
Professor Andrew Lotery at the University of Southampton has also led a group that found, in October 2014, that stem cells could be cultured from part of the cornea to become photoreceptors. “It’s easier to harvest these cells because they are very accessible – you can take a little tissue biopsy without damaging the eye, very easily,” he explains.

The future of implants

Inevitably, an area that has had a lot of coverage is retinal implants to replace the function of the lost photoreceptor cells. “In the healthy eye, photoreceptors respond to chemicals which result in electrical ‘spikes’ that are eventually carried to the brain. Retinal implants inject a direct electrical spike into the retina,” explains Professor Gary Rubin, of the Institute of Ophthalmology. “However, it’s a direct electrical stimulation using a processor, not a chemical reaction, so the brain has to get used to interpreting the new signals.” 
Different teams are exploring different forms of implant, including Professor Robert MacLaren’s team at the Oxford Eye Hospital, which is embarking on a second trial of an “epiretinal” implant, attached to the retina with a portion on the outside of the eye.
The groundbreaking work being done in the field of RP regularly hits the headlines, yet at the moment, there is still no treatment for all but two very rare forms of the condition. However, there really are grounds for optimism; that one or more projects will give rise to a widespread treatment.

Share my story

Andrew Billingham was diagnosed with RP at the age of 25, but the extent of his sight loss did not really sink in until years later.

"I was first diagnosed in my 20s, around 20 years ago. However, at the time I hardly registered it. I’d had some “floaters” in my eyes and noticed my peripheral vision had deteriorated a bit, so I went to the optician, who spotted something wasn’t quite right and referred me to the hospital. I was diagnosed with RP and told “eventually your sight will deteriorate”, but I was only about 25 and it didn’t really sink in. After that, nothing really happened much for a couple of decades. I went on working as an electrician at the time, and went self-employed at 38. I had some night blindness, but that wasn’t much. I didn’t even have regular check-ups: I learned to live with the fact my sight was getting a bit worse. 
Then about three years ago, I realised I was getting really bad headaches and dizzy spells. When I looked up, I was missing things. I didn’t know what was happening, and finally my wife pointed out I should go back to the opticians. He examined me and said: “Your RP’s got worse” and I said I’d forgotten all about it. He was actually the person who’d originally diagnosed me – he had a picture from then, and I could see how far my retina had deteriorated. At the hospital, the consultant told me: “Your results are very poor and you have very little peripheral vision, and very little central vision in your right eye.” He told me I wasn’t driving home and that I had to stop working as an electrician. In one meeting, I’d lost my job and my driving licence. I didn’t know anyone who was blind: it was completely new to me.
In the past three years, my vision has definitely deteriorated further. These days I’m registered blind and have a cane. I’ve had time to adjust, and I’ve met a lot more people who are in the same position. Fortunately, my wife works in the field too. For me, it’s the loss of a job that is the worst thing – I’ve been an electrician since I was 16.  What I really want is something to do." 

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