Thursday April 19 2012
A cell transplant allowed some night-blind mice to see in the dark
Experimental cell transplants can improve the sight of visually impaired mice, it has been widely reported. The Independent called the research behind the news a “major step towards cure for blindness”, while The Guardian said the work is “the first demonstration that cell transplants can restore useful vision”.
During the research, scientists used mice bred to lack working light-sensitive “rod cells” in the back of their eyes. These cells normally allow us to see in low-light conditions. These visually impaired mice were then injected with immature cells extracted from the eyes of young mice with normal vision in the hope that this would improve their sight. Following treatment, the mice were tested in a simple maze featuring visual indicators of the location of the exit. Visually impaired mice that were not treated struggled to find the exit, while some of those given transplants successfully identified the exit 70% of the time. The researchers concluded that treatment with these immature rod cells can improve vision, but that significantly more research is needed before this treatment would be suitable for use in people.
This early-stage research supports the continued study of immature (or ‘precursor’) rod cell injection as a possible treatment for a specific type of blindness. However, it is unknown at this stage whether similar results will be achievable in humans. Also, there are many different causes of blindness and sight loss. Even if this technique eventually reaches humans, there is no indication it would help with vision problems that are not related to rod cells.
Where did the story come from?
The study was carried out by researchers from University College London, Johns Hopkins University School of Medicine and Cornell University in the US. It was funded by the Medical Research Council UK, the Wellcome Trust, the Royal Society, the British Retinitis Pigmentosa Society and The Miller’s Trust.
The study was published in the peer-reviewed scientific journal Nature.
Generally, the media reported the story accurately, with the BBC, The Daily Telegraph, the Daily Mail and The Independent all reporting that research in humans is likely to be years away. They also correctly emphasised that the mice were not completely blind before their cell transplants but, instead, lacked the cells needed to see in low-light conditions.
What kind of research was this?
This was an animal study that examined the effectiveness of eye cell transplantation for restoring vision in sight-impaired mice.
Within the human eye, two types of light-sensitive cells work together to enable vision
- rod photoreceptors are responsible for vision in low-light conditions, or night vision
- cone photoreceptors allow us to see colours and fine details, and to see in bright conditions
When we look at an object or scene, the lenses of the eye focus light from what we are viewing onto the retina, a structure at the back of the eye that is lined with rod and cone cells. As these detect light, they produce information that is then sent down the optic nerves and decoded by the brain.
The mice used in the study had a genetic mutation that results in a lack of functioning rod cells, and these mice serve as a model for studying genetic night blindness. Mouse research of this type is commonly used to prove that the concept or theory underlying a new treatment approach is sound, and that the experimental procedures are safe. Once this is established, small-scale human studies can be undertaken to establish the effectiveness and safety of the treatment in people.
However, as this was an animal study, at this early stage of research we cannot be sure that the results will also hold true in people. In this case, it is particularly true as mice see in a slightly different way from humans. Research suggests they generally have a low number of colour-sensitive cone cells that enable full-colour vision, and instead have a higher proportion of rod cells to help them see nocturnally.
What did the research involve?
The research had two parts. First, researchers examined a group of 29 mice with the genetic mutation that results in night blindness and compared them to nine normal mice with functioning rod cells. The researchers then collected “precursor rod photoreceptor cells” from another set of normal mice aged four to eight days old with functioning rods cells. Precursor rod cells are those that have not yet matured into adult cells, although they have already started to show some of the properties that adult cells do.
These extracted precursor cells were then injected into the retinas of both the night-blind mice and the normal mice. The researchers then compared the two groups of mice in terms of how well the transplanted cells integrated into the retina and how well their retinas were responding to light.
In the second part of the study, the researchers examined whether transplanting precursor rod receptor cells into mice with night blindness resulted in improved vision. To do this they took mice with the night blindness genetic mutation and split them into two groups. The first group of nine mice received an injection of the precursor rod photoreceptor cells, and the second group of 12 mice received either a sham injection (an injection with no precursor cells in it) or remained untreated. A group of four mice with functioning rods were included in this part of the study as well. In low-light conditions, the researchers had the mice repeatedly attempt to navigate a Y-shaped water maze, which had a platform on one arm from which the mice could get out of the water. The arm of the maze containing the platform was marked with a specific pattern that mice with normal night vision should be able to see, but not mice with night blindness.
After getting out of the maze the first time, the mice that could see the pattern should have been able to recognise that it indicated the location of the platform. This would allow them to correctly identify and swim down the arm containing the platform in a series of subsequent tests. Mice that couldn’t see the pattern would just randomly pick an arm to swim down each time until they found the platform by chance. The researchers compared how many of the mice consistently passed the trial by selecting the maze arm with the pattern and platform.
What were the basic results?
In the first part of the study, the researchers found that up to 26,000 new rod cells became integrated into the retinas of the mice that had been injected with rod precursor cells. The night-blind mice injected with these cells showed similar retinal function to the mice with working rod cells.
In the second part of the study, the researchers found that:
- Four of the nine night-blind mice who had received the rod photoreceptor injection consistently passed the maze, selecting the correct arm first for at least 70% of their attempts.
- All four mice with healthy rods consistently passed the maze, choosing the correct arm first in more than 80% of their attempts.
- None of the 12 night-blind mice receiving no treatment or a sham injection consistently passed the maze. They selected the correct arm of the maze no more often than they would be expected to do by chance.
How did the researchers interpret the results?
The researchers conclude that transplanted rod photoreceptor precursors can successfully integrate into the retinas of adult mice with non-functioning rod cells, and can improve night vision.
The results of this study indicate that transplanting precursor rod photoreceptor cells into a retina with non-functioning rods can improve night vision in some mice with a very specific type of night blindness. For a variety of reasons it is unclear at this point whether such a transplant would be effective at restoring night vision in people, and it is important to view this as very early stage research. When assessing the value of this research the following must be considered.
- As with all animal studies, the results found here may not translate into similar effects in humans.
- The researchers reported that the visual functioning of the mice with night blindness was still lower after treatment than in the animals with functioning rods, and not all of the treated mice performed significantly better than untreated night-blind mice in the maze test.
- The technique will need to be adapted specifically for humans. For example, researchers will need to identify an appropriate source of similar precursor cells for humans, for example from embryonic stem cells or adult stem cells.
- The type of mouse blindness in this study, in addition to being an animal model for night blindness, was the result of a specific genetic mutation that resulted in structurally intact but non-functioning rod cells. Other types of blindness, for instance, those involving another type of photoreceptor, called cones, have not been studied here. Indeed, the mice involved in this study had functioning cone photoreceptors, which are responsible for colour vision and seeing detail in bright light conditions.
- Blindness can result from various causes, including genetic factors, degeneration of parts of the eye, or damage to the eyes, optic nerves or areas of the brain responsible for processing visual information. This treatment would not be suitable for many eye conditions that are not caused by a failure of the rod cells. For example, integration of functioning rods into the retina would not be a suitable treatment for blindness caused by damage to the optic nerve or visual areas of the brain.
This study showed that, in an animal model, treatment with precursor rod photoreceptors can lead to improved vision in mice with night blindness. As correctly pointed out by many newspapers, this research is still years away from potentially being used in people. As the study’s authors say, much more research is needed before the results of this study can be used in a clinical setting.
Analysis by Bazian