Episode 2: Understanding Vision Science: A Conversation with Dr. Abbot Clark

Joining us on this episode of the podcast is Abbot Clark, Ph.D., FARVO, Regents Professor, Pharmacology and Neuroscience, UNT Health Fort Worth, and North Texas Eye Research Institute, who will share more about his research career and glaucoma research.

Transcript

What does it actually take to
understand and prevent vision 
loss?
For many of us, eye health is
something we only think about 
when there's a problem.
Behind the scenes, there's 
decades
of research working to 
understand
diseases that can quietly
and permanently affect how we 
see the world.
In some cases, by the time 
symptoms appear,
significant damage has already 
been done.
How do researchers get ahead of 
that,
and what does it take to turn
scientific discovery into 
something
that actually helps patients?
Welcome to Eyesights,
a podcast where we explore the 
science,
people and ideas shaping the 
future of vision research.
I'm your host, Krystle Gabele, 
and today,
we're talking with someone who 
has spent his career
advancing our understanding of
eye disease at a fundamental 
level.
I'm joined today by Dr. Abbott 
Clark,
a distinguished researcher in 
Vision Science,
and a fellow of
the Association for Research in 
Vision and Ophthalmology.
Dr. Clark's work has focused on
understanding the biology, 
underlying eye diseases,
including conditions like 
glaucoma,
and how changes at
the cellular and molecular level
can ultimately impact vision.
Dr. Clark, welcome to Eyesights.
Thank you very much for the 
invitation.
I always like to start off with 
a quick ice breaker.
Since summer break is here at 
UNT Health,
what is your favorite summer 
activity?
Well, this summer, I'm looking 
forward to spending
more time with one of my dogs 
who loves the pool.
He's lab retriever, part,
German shepherd, and we can't 
keep him out of the pool.
When it's warm enough, which it 
is now,
I intend to spend time having 
him fetch
things and just getting more 
exercise in the pool.
That's fun. I know my 
sheepadoodles,
she loves being in the waters,
so it's definitely something
that we look forward to as well.
I'd love to hear a little bit 
more about your journey.
What first drew you to vision 
science?
Well, it actually happened by 
accident.
I was at UT Southwestern Medical 
School as an instructor,
and I was studying the role
of steroids and muscle 
metabolism.
I was invited to Alcon Labs
to give them an update on 
mechanism of
action of these steroid hormones 
because they were
developing an anti inflammatory 
steroid for the eye.
At the end of my presentation,
the Vice President of Research
came up and said, "Nice job.
How would you like a job here at 
Alcon?"
That started my journey into 
vision.
I worked at Alcon for 23 years,
starting as a Senior Scientist 
and then leaving as
Vice President of Research and 
Head of Glaucoma Research.
Was there a particular moment or
experience that really shaped
the direction of your research 
career?
When I was an undergraduate 
school,
I actually thought I was going 
to be
a high school teacher and 
football coach,
and I got very excited about 
science.
I've always been interested in 
science,
but particularly biology and did 
some undergrad research,
and that just lit the fire in 
me, the joy of discovery.
You've spent many years in this 
field.
What has kept you engaged and 
motivated over time?
There are several things. Again, 
the joy of discovery.
It's just wonderful to be seeing
things and learning things that
no one else has seen before.
Especially since I've been in
eye research, it's the patients.
I always think about the 
patients and how
the research that I'm doing will
hopefully lead to
better therapies for them in the 
future.
For listeners who may not be 
familiar with your work,
how would you describe your 
research
in simple terms and why it 
matters?
Well, it turns out, many 
diseases are
not really understood at the 
very basic level.
what actually damages the eye?
my research career has been
focused on trying to better 
understand
those mechanisms so that I can 
intervene in
the disease process itself
and perhaps even reverse the 
disease.
Why does it matter? Again, we 
keep the patients in mind,
And hopefully discoveries in
the lab will lead to new 
therapies for the patients.
When we think about that at the 
patient level,
what does your work ultimately
help us understand or improve?
For one thing, glaucoma is
very slowly progressive disease 
and
a leading cause of vision loss
and blindness in the world,
and that's my main focus.
I'm hoping that the work that I 
do will, number 1,
perhaps lead to better diagnosis 
of glaucoma
because 50% of patients that
have this disease are unaware 
they have this disease.
Then, again, trying to
intervene in the disease process 
so that we
can reverse the disease process 
and
let the patient have sight
through the rest of their life.
Many eye diseases like glaucoma 
can
develop gradually and without 
obvious symptoms early on.
What do you think people often
misunderstand about these 
conditions?
They deny, I think,
and the fact that many of
these diseases are slowly 
progressive and painless,
they don't realize that they're 
losing
their sight and losing it 
irreversibly.
I think when the general 
population
hears that you need eye exams 
every year,
you can't skip those eye exams,
and especially if you have
risk factors for disease like 
glaucoma.
Family history, if you are
of African descent or Hispanic,
you have a higher risk of 
developing glaucoma,
so you really need to be
seen by specialists who 
hopefully can
catch the disease early on and
allow you to have functional 
vision
through the rest of your life.
Over the course of your 
research,
have there been findings that 
have surprised you
or challenged what the field 
previously believed?
Yeah, there have been a number
of things that are surprising,
but most of them are new 
technological advances.
If you told me at the beginning 
of the career,
that I would be able to cure
a disease when a patient was 
congenitally blind,
I would say you're not being 
realistic.
I think the advances,
and as long as we keep up with 
the advances and
translate those into therapies 
that will help patients.
I think that's the main thing.
I've been fortunate to 
understand some new,
we call the pathogenic pathways,
but some signaling that occurs 
in glaucoma
that hopefully we can
intervene and block that 
deleterious signaling.
One of the biggest challenges in 
academic medicine is
translating discoveries from the 
lab into clinical care.
What are some of the barriers 
that
make this process difficult?
That's a really great question.
This one I've been struggling 
with for quite a few years.
It turns out that the FDA
requires certain sets of 
experiments
be done before you can move into 
the clinic.
A lot of those are safety 
studies.
It must be done in a very 
rigorous fashion
that academics do not have 
access to.
It's very costly to develop
these packages to present to the 
FDA,
and so you pretty much need to 
partner most likely with
a pharmaceutical company in
order to be able to afford that.
Then, unfortunately, a lot of
the clinical trials take
a long time to determine 
efficacy.
Well, first you determine 
safety,
and then you determine efficacy.
Again, it costs a lot of money 
to do that.
I think we need to work with
the National Institutes of 
Health, with the FDA,
with pharmaceutical companies to 
try and expedite
our discoveries to get
them more quickly into the 
patients.
When it does work, when 
something
moves successfully from research 
into patient care,
what makes that possible?
Generally, it's a very dedicated 
individual
pushing the discovery and 
surrounding him or
herself with a likewise 
dedicated multidisciplinary team
because you need toxicology,
you need pharmacology, molecular 
biology.
That's not possible for a single 
individual,
so I think that's the cases 
where that
works best and has worked 
successfully,
it's because of the team.
Vision science today seems
more interdisciplinary than 
ever.
How important is collaboration
across fields like neuroscience,
engineering, or data science, 
and advancing research?
It's very important as we just 
talked.
The days of doing
research by yourself in the lab 
are long gone.
The technology and the databases 
that are publicly
available now really requires
specialists in each of those 
areas,
working together on the problem.
Fortunately, with Zoom meetings 
and things like that,
you can be working with 
colleagues as I do,
for example, in Ireland,
in the Caribbean and things like 
that to again,
work together as a team.
I think you need to be aware of 
all the latest advances
and try and translate those into 
your basic research.
Communication is essential.
Both written and oral 
communication.
You can't take that for granted,
and in fact, it's very difficult 
to over communicate.
Then are there any emerging 
technologies or
approaches that you're 
particularly
excited about right now?
Yes, there are. Again,
this is a wonderful time to be 
doing science because
these advances are coming fast 
and furious.
One is big data.
There's these huge data sets 
that are being
developed so that 
epidemiologists
can go in and find associations
between genetic changes and 
clinical conditions.
There are really wonderful
new sequencing technologies that 
allow us to
actually look at a single cell
and discover what genes are 
being expressed.
You can do this in all the cells 
in a tissue.
Then I think genome editing
has really advanced the field, 
too,
to the point where it's actually 
being used in
the clinic to correct some 
diseases.
I'm really excited about all the 
technologies,
and it's really a challenge to 
keep up.
But these technologies have
so much promise that it's hard 
not to keep up.
We keep hearing a lot about 
artificial intelligence,
AI, and everything.
How do you think that that is 
going to play
a role in research,
and especially when it comes to 
the glaucoma research.
Artificial intelligence is 
really a boom to research.
It allows you to look through 
huge datasets,
allows you to predict things and 
outcomes.
You have to be careful about 
using AI, though,
because a lot of the data that's 
in
the ether world is not true, 
number 1.
Number 2, sometimes AI makes 
huge leaps that seem
reasonable until you actually go 
in
and see what they have done and 
what they're comparing.
I'm really excited about AI.
It's going to streamline a lot 
of what we do,
but we have to be cautious.
Especially with our mentees to
make sure they're not 
shortcutting,
learning how to communicate,
especially written 
communications by taking 
advantage of
AI capabilities for writing
papers and dissertations and 
things like that.
You've also mentored many 
trainees over your career.
What do you think makes someone
successful in vision research 
today?
I think curiosity and drive
are really important features 
and dedication.
I tell my students they should
rename research to be re re re 
re
research because you end up 
doing a lot of
experiments to finally get the 
answer to
the question that you were 
trying to look at.
I emphasize that every 
experiment
is a learning opportunity,
whether it works out the way you 
had intended it or not.
I think most successful ones
really have a drive to help 
people.
They try and focus their 
research
to get something translational 
to take into patients.
Then the other part of being
successful is communication 
skills.
You've got to have excellent 
writing skills,
but you also have to have
excellent presentation skills 
and
know that what you're
communicating is being received 
and understood.
For students or early career 
researchers
who might be listening,
what advice would you give them?
I would suggest follow your 
passion.
If you're passionate about 
research, stick with it.
As I said, there's a lot of 
challenges
in everyday science that's being 
done at the bench.
You have to be persistent and 
believe what you're doing.
What I mentioned earlier to 
communication is really
essential because your science
ends up not selling itself.
You have to sell your science in 
order to get funded,
in order to get noticed,
in order to get promoted,
in order to get that next job.
All of those are part of
the skill sets that successful 
scientists need.
Looking toward the future.
What areas of vision research do 
you think
will have the biggest impact 
over the next decade?
Now, it's another great question
because there are so many 
advances going on.
But I think the two that I would
focus on are gene therapy,
including genome editing and 
cell based therapy.
It's now possible to take skin 
biopsy from a patient,
convert it into a stem cell
that can develop into any 
different cell type,
correct the gene mutation that
might be responsible for that 
individual's eye disease,
and then differentiate the cells
back to the type of eye cell 
that is needed,
such as a retinal cell, 
photoreceptor,
retinal pigment epithelial cell,
and then implant that into the 
patient.
That's being done right now.
The other is, again, gene 
therapy,
and there has been a very 
successful product that,
in fact, makes kids that had
congenital vision loss, 
blindness see again.
That's by giving a normal copy 
of
what gene that individual child 
has that's mutated,
and that's able to restore 
vision.
I'm really excited about that.
Our research has actually come 
up
with two possible gene therapies 
for treating glaucoma.
With the success of gene 
therapies in the clinic,
we're very hopeful that we'll be 
able to take these
into patients and really help 
them with their disease.
What gives you the best optimism
about where the field is 
heading?
I just returned from the ARVO 
meeting,
which was held in Denver a 
couple of weeks ago.
This is the largest vision 
research meeting.
There's 11,000 individuals from 
around the world.
Just to see the excitement and 
how many people are really
dedicated to better 
understanding vision,
better understanding patients,
disease, and better treatment,
and especially a lot of
the junior folks, both graduate 
students,
post docs, young faculty 
members,
and to see their excitement,
I'm pretty confident that the 
future
looks pretty bright for fighting 
eye diseases.
Before we wrap up, I have a 
couple of quick questions.
What's one discovery in vision 
science
that you find particularly 
inspiring?
The treatment of children with 
LCA or
Leber's congenital amaurosis, 
with gene therapy,
and in fact, there's one type of
LCA that is doing in vivo genome 
editing.
Again, those patients are 
recovering
vision is very inspiring.
As I said, hopefully,
we can follow in the footsteps 
and take
some of our therapies into 
patients.
I know you mentioned this 
before,
but just for fun.
If you hadn't gone into science,
what do you think you would be 
doing?
I've always been interested in 
science,
but I've also been interested in 
teaching.
When I went to undergraduate 
school,
I went there to become a biology 
high school teacher,
as well as a football or 
lacrosse coach.
I'd still be in the science but 
teaching science.
But I really have had
a very rewarding career that I'm 
very pleased with,
and I wouldn't trade it for my 
young aspirations.
I know that that's one thing 
that I always say is,
even our best laid out pass,
always have a pivot or a change 
in there.
Absolutely. You just have
to decide which fork in the road 
to be taking.
Yeah. I went into
undergrad thinking I was going 
to be a lawyer,
and here I am as a 
communications person.
Dr. Clark, thank you so much for 
joining us.
This has been a fascinating 
conversation.
Well, thank you very much, 
Krystle.
I've enjoyed this opportunity.
If you enjoyed this episode of 
Eyesights,
be sure to subscribe so you 
don't miss
future conversations with the 
scientists,
clinicians, and trainees working
to advance vision research.
You can also learn more about
the North Texas Eye Research 
Institute
by visiting our website,
www.unthealth.edu/nteri,
where we'll also post show notes 
and
additional resources related to
each episode. Thanks for 
listening.