- [Narrator] The human brain is one
of the most studied subjects in science,
but still, much is a mystery,
including the interplay between the brain
and other organs, like the eye.
At the UC San Diego Stem Cell Program,
researchers are growing tiny brains from stem cells,
in order to further their understanding,
and they're not the only ones using this approach.
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- In order to get the complete picture
of how the brain develops, we need to understand
what happens when the brain receives
and processes sensory information from other organs,
such as the eye, and that's where Karl Wahlin comes in.
- [Narrator] The connection between the eye and the brain
has fascinated scientists for hundreds of years.
It seems miraculous that rays of light
can be transformed into a complex understanding
of the world, but sometimes, the system breaks down,
leaving people in the dark.
- Photoreceptors or ganglion cells can die,
and once those cells are gone,
those cells are gone permanently, and so,
we're looking at new ways to restore function to the eye.
- [Narrator] Karl Wahlin is the director
of the Richard C. Atkinson Laboratory
for Regenerative Ophthalmology at UC San Diego.
His lab uses stem cells to create tiny human retinas
in order to study eye disease, and hopefully,
one day, cure blindness.
- One of the power things that we can do
with retinal organoids is to introduce
patient-specific mutations, and this is something
that's really been made possible over the past five years,
by new gene editing techniques.
- [Narrator] Wahlin's lab uses
the CRISPR gene editing technique to create retinas
with the exact mutations found in people with eye disease,
so he can study how they develop,
and what treatments might work on each mutation.
- [Karl] Previously, most of the kinds of studies
that we would do to study inherited retinal degenerations
would be done in animal models, which take a long time
to develop and they're not very scalable.
The ability to make human organoids,
with disease-relevant mutations means that we can have
many mutations, we can have thousands of samples,
and we can test many of these with different drugs.
We just can't simply do this with living animals
on the same scale.
- [Narrator] He's teaming up with the Muotri Lab,
which builds brain organoids,
to study how the brain and eye
influence each other during development.
- [Karl] But we knew from decades of research
in other species that sensory input is very important
for brain development, and vice versa.
The information that we can get from this kind
of approach, the cerebral organoid retinal co-culture system
will allow us to understand how those connections are made.
There are diseases, such as Leber congenital amaurosis
in which photoreceptors died very early stage,
so this is childhood onset.
It's not clear what happens to the brain connections
once those photoreceptors are lost at a very early stage,
so if we're able to cure blindness,
this is gonna require knowledge of photoreceptor protection
as well as to understand how those connections
in the brain could potentially be perturbed.
So over time, as we've developed
this cerebral organoid retinal co-culture system,
we've recognized certain technical limitations,
and one of them is that the retinas and the brains,
they tend to be absorbed by one another,
and so, we need physical structures
in order to separate them.
(engine whirring)
Shaochen Chen's group has a lot of experience
developing biocompatible materials,
using 3D printed scaffolds, and we're using this knowledge
and their expertise, in order to build a better system.
So they've been building three-dimensional scaffold systems
for us to separate, physically separate,
the retinas and the brains, and this is gonna be
one of the critical components that we use,
in order to build a better integrated brain retina circuit.
- [Narrator] At the same time, Wahlin's lab
is looking into a treatment for eye disease
straight out of the animal kingdom.
- There's a new area in retinal research,
and it's a very fascinating area.
It's called endogenous regeneration,
and this is the process whereby specific support cells
in the eye can be reconverted into other retinal neurons,
such as photoreceptors or ganglion cells.
When you think about endogenous regeneration,
probably the most powerful example is a lizard,
or an amphibian that has lost its tail.
A lizard that loses its tail can grow a completely new tail
in a relatively short period of time.
In the eye, there's a similar situation.
Some types of fish, such as zebra fish,
have been shown to regenerate
an entirely new eye once one's lost.
In mammals, we seem to have lost this capability,
at least, naturally, to do this.
There is recent literature that suggests that this can
actually happen, if given the right instructions,
and so, our lab is very interested in taking knowledge
from other species, using this in our system,
in order to endogenously regenerate retinal neurons.
In 10 years from now, what I really hope we'll be able
to accomplish with this system that we're developing
is a platform to test new therapies.
There are hundreds of mutations which need to be addressed
and we can't do this on a case by case basis.
If we can have a system where we can study
many different mutations, and a system
that's physiologically relevant, coupled to a brain,
we would have a system where we can test new therapies
like drug discovery or gene therapies,
or, in the best case scenario, endogenous regeneration
and if it did work to cure hundreds of mutations,
this would be something that would be extremely powerful
and would transform the way medicine works.
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