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Wahid

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Cell jab restores sight in mice
Published on Wednesday 25 April 2012 16:24


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

  a.. rod photoreceptors are responsible for vision in low-light
conditions, or night vision
  b.. 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:

  a.. 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.
  b.. All four mice with healthy rods consistently passed the maze,
choosing the correct arm first in more than 80% of their attempts.
  c.. 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.



Conclusion
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.

  a.. As with all animal studies, the results found here may not
translate into similar effects in humans.
  b.. 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.
  c.. 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.
  d.. 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.
  e.. 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

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