Hi Access Indians,

Researchers Demonstrate Alternative to Stem Cells Thanks To New Method
of Synthesizing


Age-related macular degeneration (MD) is a variety of ocular disease
that affects so many millions of people, it’s downright characterized
as nothing more
than the process of aging.

In fact, the study of MD has proven itself to be so fruitful for
understanding aging as a whole, MD has become one of the first places
that scientists
have looked to in order to attempt to repair the damage of aging and
restoring youthful, or normal function.

Now in a new paper published in
Nature,
 researchers demonstrate an alternative to stem cells by creating
replacement photoreceptors from skin fibroblast cells via
pharmacological-conversion—a
process that promises to be cheaper, faster, and unburdened by ethical
and legal restrictions.

Containing the genetic code for every protein we need to build and
repair our cells, DNA can become damaged over time through the
stresses of life. Similarly
to how scratches or cracks in a CD prevent lasers from reading the
information on the disk, damaged DNA becomes difficult, and even
impossible for our
RNA (which you could imagine as the laser inside the CD player) to
read the genetic information contained therein.

“The photoreceptor is the neuron in the eye that turns on visual
circuity in response to light which enables us to have vision,” says
Sai Chavala, Ph.D.
and author of the new paper.

The loss of photoreceptors can result in MD and other retinal diseases
that lead to irreversible blindness. In this new study, however, cells
called fibroblasts
can be chemically reprogrammed to produce photoreceptor-like cells
that are now shown to restore vision in mice.


Fibroblasts are cells that help maintain the structural integrity of
connective tissues, and a reduction in fibroblast cell count leads to
wrinkled skin.

Sai Chavala and colleagues from the Center for Retina Innovation in
Dallas, Texas, found a set of five compounds that can drive embryonic
fibroblast cells
to convert themselves into retinal, rod-like, photoreceptors in both
mice and human cells.

“Stem cell-based strategies are extremely exciting,” Dr. Chavala tells
World at Large,
 but adds that generating these cells can be cumbersome and
time-consuming. Describing his strategy of chemically reprogramming
existing cells as a ‘breakthrough,’
Chavala added that the generation of the photoreceptors using his
method requires “a fraction of the time”.

In the study, these converted photoreceptors were transplanted into
the eyes of 14 blind mice to see if they would restore vision.

Owing to their nature, mice with working vision prefer dark spaces,
and so a test of whether or not the transplant was a success was
fairly straight forward;
create a bright space and a dark space and wait to see which one was
preferred by the mice.

Six mice were found to not only have restored visual function and
reflexes—notably in the pupil—but they also preferred to spend their
time in the dark
space. Chavala hypothesizes that it could have been down to how many
of the chemically reprogrammed cells survived the transplant into the
retina that
determined whether vision was restored in the mice or not.

What makes interventions like these—which involve creating brand new
cells to replace the damaged ones—so effective and exciting in the
field of aging
is that they present an alternative to natural replication by
bypassing the difficulties that our own cells have with trying to
repair themselves from
DNA that features double-strand breaks or other blemishes.


Reasons to be hopeful

Adding that these conversions of fibroblasts to photoreceptors has
also been done in humans, Chavala detailed why he believes the
treatments and future
research to spring from this discovery are going to change the field
of ophthalmology.

“ We believe this can be a game changer in the field of regenerative
ophthalmology. We also believe this is a platform technology and have
already started
establishing protocols to generate retinal ganglion cells valuable for
patients suffering from glaucoma,” says Chavala.

In addition to bypassing the ethical and political restrictions and
hiccups with using embryonic human stem cells, the process takes two
weeks, costs less,
and is more scalable than using stem cells.

“It is intriguing to postulate that the addition of other molecules or
modifications to the culture conditions can yield other types of
neurons beneficial
for a variety of neurological diseases,” he adds, discussing possible
alternatives to photoreceptor generation from fibroblasts.

Chavala is rapidly approaching human trials and hopes to have an
FDA-approved treatment out the other end of the pipeline in 2-3 years,
saying he is “thrilled”
with the possibility of allowing millions of people to regain their lost vision.




-- 
Ronald Jason Escrader.




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