Using Stem Cells to Treat Macular Degeneration - bli

By Jawad Braick
Macular degeneration is progressive loss of vision to the point of legal
blindness due to damage to the macula, the part of the eye responsible
for detailed, sharp vision.
The macula contains photoreceptor cells, which take in light, and retinal
pigmented epithelium (RPE) cells, which nourish the photoreceptors
Macular degeneration begins to occur when RPE cells die and are unable
to nourish the photoreceptors and in turn, they die and light isn’t taken
in at that area of the eye.
Macular degeneration characterized by progressive loss of fine acuity
vision in the central portion of the visual.
Macular degeneration comes in two forms: agerelated macular degeneration, AMD, and stargardt’s
AMD is as a result of dyeing photoreceptor and RPE
cells that occur because of the natural aging process.
Stargardt’s disease is caused by dyeing
photoreceptor and RPE cells due to a genetic
mutation. There are two forms of stargardt’s disease.
The most common form of stargardt’s disease is the
recessive form caused by a mutation in ABCA4 gene.
The ABCA4 gene is located on the short arm of
chromosome 1 in position 22
More than 500 mutations in this gene have been
known to cause macular degeneration, most of which
change single amino acids
The damage to photoreceptor cells is caused by
the build up of toxic substances in the cell
When light enters the retina and is converted to
electrical signals, phototransduction a substance
called N-retinyl-phosphatidyletholamine (NR-PE)
is produced as bi-product. A protein called
flippase is supposed to bring NR-PE out of the
cell but if this protein is malfunctioning NR-PE
builds up in the cell
NR-PE then combines with another molecule to
produce lipofuscin, a toxic substance which
causes damage to the cells and they will
eventually die.
The rarer form of Stargardt’s Disease is the
dominant form caused by a mutation in the
EVOVL4 gene
The EVOVL4 gene is located on the long arm
of chromosome 6 in position 14. At least 3
mutations in this gene have been known to
cause macular degeneration.
Death of the photoreceptor and RPE cells can also
be caused by interference with cell functions.
The EVOVL4 gene codes for the protein elongase.
Its job is to assist in the formation of very longchain fatty acids by adding carbon molecules.
A mutated EVOVL4 gene sends premature signals
in the instructions to make elongase. As a result,
the protein is unable to stay in endoplasmic
reticulum and clumps together (aggregates).
These aggregates can not make very long-chain
fatty acids can interfere with other cell functions
and cause cell death.
A stem cell is a self renewing cell capable of differentiating into a specialized
Pluripotent stem cells-stem cells that can differentiate into most cell types
Multipotent stem cells- stem cells that differentiate into a few cell types
Induced Pluripotent stem cells (iPS)-specialized cells that were reverted back
to pluripotent stem cells
Embryonic stem cells-pluripotent stem cells from an embryo
Adult stem cells- multipotent stem cells from various areas of an adult body
The eye is one of the few areas of the body that is immune
privileged. This means that the immune system isn’t very active,
in the eye.
Immune privilege is characterized by the ability to tolerate
antigens without eliciting an inflammatory immune response.
Some mechanisms that maintain immune privilege in the eye are
physical barriers, the inhibitory ocular environment, and the
ability to regulate systemic immune responses.
Immune privilege allows stem cells to work to
their full potential.
Usually implanted stem cells are rejected by
the body and are recognized as antigens by
the immune system, whether they are from a
donor or the patient themselves. As a result,
immune system attacks and destroys the
stem cells.
Scientists hope to inject embryonic stem cells
into the macula then the stem cells would
differentiate into RPE
Also scientists, want to inject embryonic stem
cell-derived RPE cells into the macula rather
have them differentiate after being injected
Two phase 1 trials were conducted in which
two patients were injected were embryonic
stem cell-derived RPE cells into one eye. One
had AMD and the other had Stargardt’s
Both patients tolerated the treatment well and
said they had improved vision in the treated
The inserted stem cells could proliferate and
form a tumor
Even though the eye is immune privileged the
immune system could still attack and destroy
the stem cells
The cells may not integrate and function due
to damage in tissue

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