‘Transplanting retinal tissue in end-stage retinal degeneration helps restore vision by forming structured outer nuclear layers in the retina.’
Retinal degeneration is mostly a
hereditary disease that eventually leads to blindness. It is characterized by
the death of photoreceptors, which are the light-sensitive neurons in the eye.
In end-stage retinal degeneration, the outer nuclear layer of the retina
is completely missing and most of the photoreceptors are dead. As a result, the
neurons do not have any input and no signals are carried to the brain.
There have been many attempts to treat
the disease through retinal transplants
Some studies have also shown that transplanting
graft photoreceptors to the host
cells can rescue retinal function. Host cells are the bipolar retinal cells.
They exist between the photoreceptor
cells and ganglion cells.They send signals to the brain via ganglion cells.
But, to date, there has been no success
in transplanting photoreceptors that functionally connect to host cells and send visual signals to host retinal
3D Retinal Sheets
The research team led by Masayo
Takahashi and Michiko Mandai of the RIKEN Center for
studied end-stage retinal degeneration using a mouse model.
The team has shown that to restore normal
structure connectivity in the retina, 3D retinal sheets derived from mouse induced pluripotent stem cells
(iPSCs) can be used.
Skin cells taken from adult mice were genetically reprogrammed
to an embryonic stem cell-like state, and then converted these iPSCs into
When transplanted into mice with end-stage
retinal degeneration, the iPSC-derived retinal tissue developed to form photoreceptors
that established direct contact with neighboring host cells in the retina.
method was a key point," explains first author Michiko Mandai, "Transplanting
retinal tissue instead of simply using photoreceptor cells allowed the
development of more mature, organized morphology, which likely led to better
responses to light."
After integrating some modifications to
both the retinal sheets and the model mice, the research team assessed the
success of transplantation.
The ends of the photoreceptors connect to
the host neurons, which are the bipolar retinal cells and they send visual
signals to the brain.
The research team used a fluorescent
protein to label the ends of the photoreceptors. Another fluorescent
protein was used to label the host retinal bipolar cells.
They found that the labeled cell
terminals from the graft did indeed make contact with the cells labeled in the
host, indicating that the newly grown photoreceptors naturally connected
themselves to the bipolar cells in the model mice.
Mice with normal vision can learn to
associate sounds or light with different events, the same way that Pavlov's
famous dog associated food with the sound of a bell.
To assess whether the mice could see
light, the researchers used this behavioral learning task.
Before surgery, the model mice that
lacked a photoreceptor layer in their retinas could not learn to associate
anything with light.
But after the transplant, they were able to learn, provided that a substantial amount of
the transplant was located in the correct place.
This means that not only did the new
cells in the retina respond to light, but the information traveled to the brain
and could normally be used to learn.
"These results are a proof of
concept for using iPSC-derived retinal tissue to treat retinal
degeneration," says Mandai.
The research team cautioned that this therapy is
still at its developmental stage. "We cannot expect to restore practical
vision at the moment," Mandai explains. "We will start from seeing a
simple light, then possibly move on to larger figures in the next stage."
make the findings more human-friendly before clinical trials, the team
hopes to conduct a few more studies using human iPSC-derived retinal
tissue in animals
with end-stage retinal degeneration.
Clinical trials are the only way to
determine how many new connections are needed to restore vision.
Photoreceptor Cells in
A photoreceptor cell is a specialized
type of neuron found in the retina. Photoreceptors absorb and convert light
into electrical signals.
These signals are sent to other cells in
the retina and ultimately through the optic nerve to the brain where they are
processed into the images.
The two classic photoreceptor cells are rods
are rod-shaped cells in the outer regions of the retina that are responsible for peripheral and
reside mostly in the central portion of the retina, and are responsible for central vision
are two types of degenerative conditions of the retina
Age-Related Macular Degeneration (AMD)
is a degenerative eye condition, leading to loss of vision among people aged 50
and older. It causes damage to the macula, a small spot near the center of the
may advance slowly or rapidly and the loss of vision depends on the disease
common symptom of AMD is blurred area near the center of vision, which
progresses to a blank spot. Over time, the blurred area may grow larger and
objects also may not appear to be as bright as they used to be.
loss of central vision in AMD interferes with simple everyday activities, such
as the ability to see faces, drive, read, and write.
pigmentosa (RP) refers to a group of inherited diseases caused by gene
mutations. It is inherited from one or both parents.An estimated 100,000 people
in the U.S. have RP.
causes retinal degeneration affecting the retina's ability to respond to
light.The photoreceptor cells (rods and cones) in the eyes slowly die due to
causes slow loss of vision, beginning with decreased night vision and loss of
peripheral vision eventually leading to blindness. There is no cure for RP.
Only the disease progression can be slowed.
- Masayo Takahashi et al. iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice. Stem Cell Reports; (2017) doi.org/10.1016/j.stemcr.2016.12.008
- Photoreceptor Cells (Photosensitive Cells) - (https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024257/)
- Age-Related Macular Degeneration (AMD) - (https://nei.nih.gov/health/maculardegen)
- What Is Retinitis Pigmentosa? - (https://www.aao.org/eye-health/diseases/what-is-retinitis-pigmentosa)
- Retinitis Pigmentosa - (http://www.blindness.org/retinitis-pigmentosa)