UCL scientists have carried out the first successful transplant
of light-sensitive photoreceptor cells extracted from a synthetic
retina, grown 'in a dish' from embryonic stem
cells.
When transplanted into night-blind mice these cells appeared to
develop normally, integrating into the existing retina and forming
the nerve connections needed to transmit visual information to the
brain.
The study, funded by the Medical Research Council, suggests that
embryonic stem cells could in future provide a potentially
unlimited supply of healthy photoreceptors for retinal cell
transplantations to treat blindness in
humans.
The loss of photoreceptors - light sensitive nerve cells that
line the back of the eye - is a leading cause of sight loss in
degenerative eye diseases such as age-related macular degeneration,
retinitis pigmentosa and diabetes-related
blindness.
There are two types of photoreceptor in the eye - rods and
cones. Rod cells are especially important for seeing in the dark as
they are extremely sensitive to even low levels of
light.
Previous work by Professor Robin Ali and his team at the UCL
Institute of Ophthalmology and Moorfields Eye Hospital has shown
that transplanting immature rod cells from the retinas of healthy
mice into blind mice can restore their sight. However, in humans
this type of therapy would not be practical for the thousands of
patients in need of treatment.
Using a new laboratory technique involving 3D culture and
differentiation of mouse embryonic stem cells, which was developed
recently in Japan, Professor Ali's team were able to grow retinas
containing all the different nerve cells needed for
sight.
Professor Ali said: "Over recent years scientists have become
pretty good at working with stem cells and coaxing them to develop
into different types of adult cells and tissues. But until recently
the complex structure of the retina has proved difficult to
reproduce in the lab. This is probably because the type of cell
culture we were using was not able to recreate the developmental
process that would happen in a normal
embryo.
"The new 3D technique more closely mimics normal development,
which means we are able to pick out and purify the cells at
precisely the right stage to ensure successful transplantation. The
next step will be to refine this technique using human cells to
enable us to start clinical trials."
The researchers grew retinal precursor cells using the new 3D
culture method and compared them closely with cells developed
normally, looking for different markers at different stages of
development. They also carried out tests to look at the genes being
expressed by the two types of cells to make sure they were
biologically equivalent.
They then transplanted around 200,000 of the artificially grown
cells by injecting them into the retina of night blind mice. Three
weeks after transplantation the cells had moved and integrated into
the recipient mouse retina and were beginning to look like normal
mature rod cells. These cells were still present six weeks after
transplantation. The researchers also saw nerve connections
(synapses), suggesting that the transplanted cells were able to
connect with the existing retinal circuitry.
The paper, Photoreceptor precursors derived from three-dimensional embryonic
stem cell cultures integrate and mature within adult degenerate
retina, is published in Nature
Biotechnology.