>> Tom Zinnen: Welcome, everyone, to Wednesday Nite at the Lab. I'm Tom Zinnen.
I work here at the UW Madison Biotech Center and UW Extension Cooperative Extension. And on behalf of our sponsors,
Wisconsin Public Television and Wisconsin Alumni Association, welcome to Wednesday Nite at the Lab.
We do this every Wednesday night, 50 times a year. Tonight I'm delighted to be able to introduce to you Dr. Aparna
Lakkaraju. She's an assistant professor in ophthalmology and visual sciences here at UW Madison.
She earned her bachelor's degree in pharmaceutical sciences at Kakatiya University in India and her PhD from the University of
Minnesota in the Twin Cities. She completed her postdoc training in cell biology and ophthalmology at Cornell
University's Weill Medical College in New York City. She moved to UW Madison from New York just a year ago
to set up her own lab here. Her research is geared towards understanding the pathogenesis of retinal degeneration,
specifically age-related macular degeneration. In her lab, Dr. Lakkaraju uses high resolution and high speed
microscopy of living cells to see how they respond to aging and to stress. Her funding comes from support
from the American Health Assistance Foundation, the Research to Prevent Blindness Foundation, and the Karl
Kirchgessner Foundation. Please join me in welcoming Dr. Lakkaraju to Wednesday Nite at the Lab.
[APPLAUSE] >> Aparna Lakkaraju: Good evening, everyone. I would like to thank Tom and
the organizers of Wednesday Nite at the Lab for inviting me here. And I would also like to thank you for coming on such a
beautiful night. What I would like to do today is to start with a brief introduction about how we see
and then focus the majority of my talk on age-related macular degeneration which is the most common cause of blindness among
older people worldwide. So our eye is like a camera. Just as light passes through the lens of the camera and is
focused on the film to produce a photograph, similarly light passes through the cornea and the lens in the eye and is
focused on the retina to produce the image that we see. And just as the quality of the film dictates the quality of the
photograph that we get, the health of the retina dictates how well we see. The human retina is the
light-sensing part of the eye. And it is composed of seven different types of cells arranged in three layers.
And light has to pass through these three layers and hit the very back of the retina where these cells called
photoreceptors are present. And light hits these photoreceptor outer segments which are composed of flattened
sacks of membrane called disks. And these disks contain, sorry about that, these disks contain the visual pigment or opsins.
So when a photon of light hits opsin, opsin gets isomerized and this converts the light signal into an electrical signal that
is then transmitted through these neurons to the brain via the optic nerve fibers. Now, sitting beneath the
photoreceptors is a layer of cells called retinal pigment epithelium about which I'll be talking a lot today.
Now developmentally, both the neural retina and the pigment epithelial cells are formed from an outgrowth of the diencephalon
in the brain called the optic vesicle which invaginates to form the optic cup, shown here, and the outer layer forms the
retina and the inner layer forms the pigment epithelium. There are two types of photoreceptors in our eyes, rods
and cones, and they're so called because the of the shape of their outer segments. Rods are cylindrical and cones
are cone-shaped. Now, cones are responsible for high resolution color vision, and they're highly metabolically
active. And if you see here, the highest density of cones is the in the central part of the retina
called the macula. Rods are responsible for low light gray-scale vision, and they're not as metabolically
active. And in our eyes we have about 20 times as many rods as we have cones.
Now, the retina is a very high-performing tissue. So you think of it like a Ferrari.
So it's a high-performing tissue, it requires high maintenance. And small disturbances can
severely impact the functioning of this tissue. Now, of the many disorders that affect different parts of the
eye, age-related macular degeneration, or AMD, is especially devastating because it affects the light sensing
part of the eye and there are no good therapeutic options for this disease. Now, vision loss, of course,
comes with a huge social burden because it takes away our independence and severely impacts our quality of life, but
it also comes with a huge economic burden. And the economic burden of vision loss in the United States
is about $51.4 billion in annual costs. So what exactly is age-related macular degeneration?
Like I just mentioned and like its name suggests, it affects the macula of the part of the eye which is highly rich in
cones and is responsible for fine high resolution vision. So, for example, those of us in this room with normal vision can
clearly see the faces of these two boys, but those with macular degeneration see something like this.
And perhaps we can really understand how AMD affects vision by seeing the works of artists who had this disease.
This is a painting by Edgar Degas in 1865 when he was a young man. And you can see the fine details
in this painting, like the features in this woman's face and the details in these flowers, but about 35 years
later you see, when he had macular degeneration, you see how the details are kind of blinded and also the colors, he
does not paint them as vividly as he did in this painting. And this is a painting by Georgia O'Keeffe in 1930 and
this is about 40 years later when she had severe age-related macular degeneration and she could the not see and she
basically was painting from memory. So AMD comes in two types, wet AMD and dry AMD.
Wet is also called advanced AMD. It is sudden onset and it causes severe vision loss. It happens in about 10% of the
patients, and it is caused because of abnormal growth of blood vessels into the retina. And the earliest sign of wet AMD
is that straight lines appear wavy Now, dry AMD is a slow decline in vision and that occurs in about 90% of the
patients and it is caused by accumulation of proteins and lipids underneath the pigment epithelial cells that I just
mentioned. And the earliest symptom of dry AMD is blurred vision. So one of the quickest ways to
diagnose any problems in central high resolution vision is the use of the Amsler grid. So when you go to our
ophthalmologist's office, you're shown a piece of paper with a grid that looks like this. And you're asked to put it at
the normal reading distance and close one eye and focus on the central spot that you see here. And most of us with normal
vision should see these lines quite clearly. But if there are any problems at central vision, people see
something like this. So the straight lines appear wavy as in the case of wet macular degeneration when
there's a growth of appear normal blood vessels that actually grow into the retina and lift the retina up so the
image that falls on the retina is not that the straight lines but of wavy lines. And then there is dry AMD, that
is the deposit of proteins and lipids, both within and underneath the pigment epithelial cells you have
blurred vision because the quality of the image that has formed is not so sharp. Now, one of the complicating
features of AMD is that it is not a linear disease. So what scientists have put forth is this multiple -- model.
So age, of course, is the single biggest risk factor for the disease. And it's not just age but age
coupled with genes and environmental and lifestyle choices such as smoking, high fat diet, high blood pressure,
obesity, and genes involved in inflammation, cholesterol, metabolism, and oxidative stress all conspire to dictate whether
a person gets macular degeneration or not. Now, what are the current treatments for this disease?
For dry AMD there are no approved treatments, and what we can do is try and prevent the disease by lifestyle choices,
such as stopping smoking, decreasing body mass index, and controlling hypertension, and also using high doses of
antioxidants that I'll talk about later in the talk. And for wet AMD, in addition to lifestyle choices, there are
therapies that are available that can actually prevent the growth of blood vessels. There are, however, a number of
drugs that are currently in clinical trials for dry AMD. And these are mainly antioxidants, anti-inflammatory
agents, and drugs that interfere with inflammation, both systemically and within the eye and also neuroprotective agents.
So what causes AMD? Like I just mentioned, it's a multifactorial disease so there is no one cause.
So in addition to age, family history, and smoking, smoking is the only confirmed risk factor for AMD.
There are genes involved in inflammation, such as complement factor H, complement factor B, and genes involved in
cholesterol metabolism, like apolipoprotein E, that have all been implicated in macular degeneration.
But exactly what happens, no one really knows because these factors like environmental factors, age, genetic factors,
all combine to somehow lead to both dry and wet AMD. While the exact cascade of events is not clear, what is
generally believed now is that the initiating factor is damage to the retinal pigment epithelial cell.
So what are these retinal pigment epithelial cells. The RP is a single layer of cells that sits beneath the
photoreceptors and the choroidal circulation, and these cells perform many functions that are absolutely indispensable for
vision. For example, they have what are called tie junctions between the cells, and these form the outer
blood/retinal blood barrier which is similar to the blood/brain barrier that you may have heard of.
And what it does is it controls the flow of nutrients and metabolites into and out of the retina.
RP cells also have pigment granules, melanin granules, that absorb stray light and improve the quality of the image that we
see. The sacred growth factors and extracellular matrix components both for the health of the
photoreceptors and the capillaries and they also participate in the visual cycle by recycling retinoids.
So if you think, going back to our Ferrari analogy, if you think of the retina as a Ferrari, you can think of the
retinal pigment epithelial cells a one-stop service station that is absolutely essential for the smooth running of your Ferrari.
So one of the most important functions that the pigment epithelial cell does is the daily phagocytosis and
degradation of photoreceptor outer segments. Now, why is this important? So like we just saw,
photoreceptor outer segments are composed of these types of membrane that have the visual pigment opsin.
And a photon of lights hits opsin gets isomerized and that's how the light signal is converted to a electrical
signal. So because these outer segments are constantly exposed to light, they are susceptible to
oxidative damage. So to counter this, what happens is every day all these photoreceptors in our eyes shed
about 10% of their outer segment length, and these outer segments are then taken up and digested by the underlying RP cell.
Now, each RP cell in our eye takes care of about 30 to 40 photoreceptors. So you can imagine what a huge
metabolic burden this is. It's like eating a hundred bagels for breakfast every day for our entire lives.
So what happens is over time undigested proteins and lipids accumulate in the RP, and they accumulate in these compartments
called lysosomes. So in a cell that normally divides, if there is undegraded protein or some kind of junk
that accumulates in the cell and the cell divides like the cells that like our skin or the cells that line our intestines, that
junk gets diluted among daughter cells and it can be kept at low, nontoxic levels. But a significant feature of the
pigment epithelial cells and also the photoreceptors is that they don't divide. So we only have what we are born
with. So what happens is over time this junk keeps accumulating in our eyes and it has nowhere to
go. So this accumulation of lysosomal waste is called lipofuscin.
It comes from Greek and Latin, and it's called dark fat and it's also called age pigment because it starts accumulating
in all our eyes pretty much from the minute we start seeing. So only one component of RP lipofuscin has been structurally
characterized. And it is called A2E. And that's because it's because formed as a byproduct of the
visual cycle and it's an additive of two molecules of vitamin A and one molecule of ethanolamine which is a lipid
present on cell membranes. Now, if you look at the structure of this compound it's full of carbon-carbon double
bonds. So there is no known enzyme that can degrade this and it also cannot be sent out of the cell.
So it accumulates in our eyes throughout life, and in some cases it can reach about 20% of the cell mass.
And it's higher in inherited macular degeneration such as Stargardt or Best diseases. So with age, like I just
mentioned, the RP becomes less efficient at digesting these photoreceptor outer segments and two kinds of deposits accumulate
in these cells. One within the RP lysosomes, which we just looked at called lipofuscin, and another beneath
the pigment epithelial cells called drusen. And both these deposits are hallmarks of dry AMD.
And they slowly accumulate in our eyes, and when you go to the ophthalmologist's office he can actually look at your retina
through an ophthalmoscope and look at the size and the characteristic of these drusen. And there are actually criteria
that they've established where if the drusen is bigger than a certain size and if their edges are soft versus the edges are
hard, then those are the risk factor for macular degeneration. Now, and of course neovascularization or the growth
of new blood vessels from the choroidal capillaries into the retina cause hemorrhage within the retina and this causes wet
AMD as we have just seen. So, I just want to talk briefly about what we are doing in my lab and that is based mainly on
accumulating evidence that many age-related diseases have common features. For instance, Alzheimer's
disease, which is characterized by the accumulation of beta amyloid in the brain, has that in common with age-related
macular degeneration because people have found beta amyloid also beneath the RP in AMD eyes. And statins which are widely
used to treat atherosclerosis and cardiovascular disease have recently been shown to improve memory in Alzheimer's patients.
But one feature that is really common among all these diseases is a disturbed metabolism of cholesterol and inflammation.
And in macular degeneration over the last several years, several genes that are involved in the synthesis, the transport, and
the metabolism of lipoproteins like LDL and HDL have all been implicated in this disease. And postmortem analysis of AMD
eyes has shown that in drusen, which are these huge deposits that accumulate beneath the pigment epithelium, these are
actually rich in cholesterol, as you can see here. And scientists have also created mouse models but have knocked
out or over-expressed certain cholesterol metabolizing enzymes or lipoprotein receptors. And many of these models
actually show retina abnormalities, both functionally and morphologically. So cholesterol is a central
lipid in our cells, and it's very essential for making cell membranes. It's important for protein
function, it's important for protein transport, and it's important for keeping traffic within the cell flowing
smoothly. But when cholesterol levels are high in the cell, it makes membrane very rigid.
And it also jams traffic within the cell, and it causes proteins to aggregate. And when cholesterol levels are
really high, you can have cholesterol crystals and these are actually crystals isolated from arteries with
atherosclerosis You can see how sharp and pointed they are so they can actually poke holes in cell membranes, cause
inflammation and cell death. So we can use several different approaches to study vision diseases.
One is we can study human eyes so we can image the human eye and try to tease out what genes or lifestyle choices lead to the
disease. We can model the disease in animals, and what we do in my lab is we try to understand the
disease at the level of a cell. And this is because, broadly, a disease can be characterized as dysfunction at the level of the
cell which is then manifested at the level of the organism. And so if you understand, if you can identify what the protein,
the lipid or the organelle is affected in the disease, then this can help us identify potential therapeutic targets
and then we can actually design effective therapies to treat the disease. Now, the cell is an efficient
factory. So our bodies are composed of organs, all these organs are composed of cells, and cells in
turn are composed of small compartments which carry out very specific functions that are absolutely essential for the
functioning of the cell. For instance, the nucleus is where genes is expressed. The endoplasmic reticulum is
where proteins are made. The mitochondria are the energy power houses of the cell. And these organize knells called
lysosomes are very important because they function as the garbage disposal system of the cell.
So in the retinal pigment epithelial cell, outer segments which are phagocytosed taken up every day and degraded, this
degradation happens in lysosomes. And because over time, like I just mentioned, the efficiency
of this degradation goes down, undegraded proteins and lipids accumulate and this is called lipofuscin.
And this also happens in lysosomes. Now when cells take up lipoproteins like LDL and HDL,
the cholesterol that is taken up into cells goes to lysosomes and it is then cleaned and the free cholesterol is then sent to
different parts of the cell. So what we initially hypothesized was because lysosomes are the sites where
phagocytosed outer segment disks are metabolized, internalized LDL and HDL is metabolized and is also where lipofuscin forms.
We asked whether the formation of lipofuscin in the pigment epithelial cell interferes with cholesterol metabolism in the
pigment epithelial cells. So what we first did is we cultured these cells in the lab in Petri dishes and we stained
for cholesterol. And we did this by using this dye which binds cholesterol and glows blue when you shine
ultraviolet light on it. And you can see here that in healthy cells this staining is pretty much on, the blue stain
is pretty much on the cell membrane and you find a little bit inside the cell. But in cells that have the
lipofuscin component A2E that I just mentioned which is formed as a byproduct of the visual cycle which accumulates in all
our eyes, you can see that there's a huge increase in the blue signal. And this blue signal colocalizes
or is found in the same spot as the red fluorescence of A2E. So what this told us was that the presence of lipofuscin or
A2E in RP lysosomes leads to the accumulation of cholesterol in these cells. And when we looked biochemically
at the total levels of phospholipids, single myelin or cholesterol in these cells, we found that there was a
significant increase of cholesterol in the retinal pigment epithelial cells when in the presence of lipofuscin or
A2E. And what we also followed was the clearance of how well these cells clear cholesterol that
they take up as part of outer segments that they take in every day. And you can see that in the
yellow in healthy cells the cells are able to clear cholesterol that they take up every day within 24 hours, but
in cells that have the lipofuscin component, there's a significant delay in the clearance of these outer
segments. Now there are drugs that are available on the market that actually increase the expression
of proteins that are cholesterol transporters that help cholesterol leave the cell. So what we did was we treated RP
cells with these drugs. And here you can see that this shows the expression of this protein called ABCA1 which is a
transporter for cholesterol. It actually takes cholesterol from inside the cell and sends it out to HDL, for instance,
which is in the circulation. And when used these drugs, either Pioglitazone or a compound called TO, there's a
huge increase in the expression of these proteins. And when we went back to the assay that I just showed you
where we stained the cells with this compound called filipin to see where the cholesterol was located, you can see, again,
once again in the presence of A2E there's a huge increase of cholesterol in the cells. But in cells that have A2E that
we treated with these drugs, we were successful in sending cholesterol out, suggesting that you treat these cells with drugs
that help cholesterol leave, get cholesterol back to normal levels. So what we are studying now is
this protein called apolipoprotein E which is a very interesting protein because it occurs in three forms in humans:
APOE2, E3, or E4. And these three forms differ in only one amino acid. And they're characterized by
different affinities for the LDL receptor. It is a cholesterol transporting protein, and the really
interesting thing about this protein with regard to macular degeneration is that the people with E2 are supposed to have a
20% increased risk of getting the disease, while people with E4 have a 20% protective effect. Now, this is exactly opposite to
Alzheimer's disease. APOE is a conformed risk factor for Alzheimer's disease and APOE2 is protective and APOE4 is
a risk factor. So it's almost like pick your poison whether you want to have Alzheimer's disease or AMD.
And APOE has also been found to be highly abundant in drusen, these huge deposits beneath the RP that I talked about.
And so make matters even more confusing, what scientists in North Carolina did was they took a mouse and they knocked out the
APOE that the mouse expresses and they put in the human form of APOE2, 3, or 4, and they fed these mice either a regular diet
or a high fat diet. And they found that mice that have APOE4 on a high fat diet actually have many features of
macular degeneration such as blood vessel growth into the retina and deposits beneath the RP.
So what we thought was let us look at what these three isoforms are doing at the level of the pigment epithelial cell
because no one has really seen that before. So for this, what we use is high resolution high solution, high
speed microscopy and we use a technique called spinning disk confocal microscopy. Now, conventional microscopy,
which is a wide field where you scan your sample, you shine light on your sample, and you are not only seeing the part of
the sample that is in focus, but you also have out of focus light which significantly reduces the quality of the image that you
see. And then the next development of this was laser scanning confocal microscopy where, instead of
signing light on the entire sample, you shine light on a thin sliver of the sample using a pin hole and the microscope
then scans a sample point by point so you can get an image of the entire cell. What we are using is a spinning
disk confocal microscope. So instead of the single pin hole in the confocal, we have a disk which has thousands of pin
holes, and this rotates very fast, it spins very fast, and shines these thousands of pin holes on your sample and this is
coupled with another disk which has micro lenses, thousands of micro lenses. So the light then goes back to
the this lens disk and then is captured by a high resolution camera. So helps us capture extremely
fast events in living cells in realtime. So what we did here was that we took APOE2, APOE3, or APOE4
genes expressed in proteins and tagged them with green fluorescent protein, which is a protein that is expressed by
jelly fish and it fluoresces green when you shine blue light on it. And we expressed these in
pigment epithelial cells. And you can see, and this is a realtime image, and you can see how the three different proteins
have three different morphologies. So APOE2 is mostly seen in these long tubes that traffic
throughout the cell. APOE3 is found in tubes and these small little punctate dots.
And APOE4, you don't see many tubes but you see mostly these huge vesicles or bubble-like things that go back and forth in
the cell. So what we expect is that if we study how these three proteins function and move within the RP
cell in living cells, it will give us an idea about what these three proteins may be doing inside the cell and help us
understand the disease at the level of the organism. And what is the relevance of understanding what these three
APOE forms are doing in the RP? In addition to transporting cholesterol in and out of the cell, APOE isoforms in the brain
have been shown to help in the clearance of beta amyloid. And because beta amyloid has also been found beneath the RP
in AMD eyes, this can dictate susceptibility to AMD and disease progression. Now, APOE isoforms have also
been shown in cardiovascular disease to dictate the response to statins. So people who express APOE2 have
a better response to statins than people who express APOE4. And because statins have been suggested as possible drugs to
prevent AMD, in fact there are a lot of epidemiological studies which are quite confusing, there is no clear consensus on the use
of statins in AMD. So perhaps if the data were looked at on the basis of what type of APOE type people
express, may be that would give us a clear idea about whether the statins are really helpful in AMD or not.
And finally, many of you must have heard about lutein, zeaxanthin and -- as antioxidants to prevent AMD and
this also because APOE isoforms dictate whether they bind HDL or LDL, and because HDL is the major lipoprotein that delivers
carotenoids to the retina, this will again dictate how well these lutein and zeaxanthin go into the retina.
So this is very important to study what APOE isoforms do at the level of the retina and the retinal pigment epithelial cells
to understand how people may be, A, susceptible to the disease and, B, what we can do to prevent it.
Now, like I mentioned, these late endosomes and lysosomes, I asked you to keep these in mind because they're the garbage
disposal system of the cell. So this is another thing we're studying in my lab mainly because the efficiency of this
garbage disposal system declines with age in the pigment epithelial cells. And this is partially why the
deposits accumulate, leading to dry macular degeneration. And one other important feature about this garbage disposal
system is that when the cells have high levels of cholesterol, it has been shown in Alzheimer's disease and in cardiovascular
disease that the efficiency of the garbage disposal system goes down. Again, because cholesterol jams
traffic within the cell and does not let different compartments in the cell talk clearly to one another.
So one protein that we're looking at is this protein called Niemann-Pick C1, or NPC1, and it is mutated in a disease
called Niemann-Pick type C disease and this is characterized by progressive neurodegeneration and huge
accumulation of cholesterol and other lipids in lysosomes. And there are not many studies about what this protein does in
the retina mainly because the children with this disease are characterized by extreme mental retardation and few survive into
adulthood. But there have been some studies in fruit flies and in mice showing that when this protein
is mutated it can actually cause retinal abnormalities. So, again, for this we use the spinning disk confocal
microscope that I told you about, and we took Niemann-Pick C1 protein and tagged it with the green fluorescent protein,
expressed it in retinal pigment epithelial cells. And here in healthy cells you can see that there are these
long tubes that go from one part of the cell to the other, almost like ants zipping back and forth through the cell transporting
cholesterol and other cargo. But in cells that have lipofuscin or A2E, there is very little traffic.
It's almost as though the cell is paralyzed. It can't really see much. There's not many things that
move around. So if you do a still image of this, what we saw was that in healthy cells there is a tube
that buds from this little dot here and zips across and fuses with another little vesicle in the cell within 180
milliseconds. But in cells which have A2E or the lipofuscin compound there is almost no traffic.
So what this tells us is that accumulation of lipofuscin with age in the retinal pigment epithelial cells causes an
accumulation of cholesterol. And this kind of paralyzes traffic within the cell, preventing the transport of
proteins and lipids to their proper destinations. So what we hope is that by studying what happens with age
and stress and in disease at the level of the RP cell, we can understand what exactly happens in the cascade of events that
lead to vision loss, and this will help us identify possibly potential treatments and that we can then develop to treat the
disease. So there is another really confounding factor with AMD is in that is HDL good or bad?
Because in a lot of studies, epidemiological studies have come out showing that high cholesterol levels are
protective for the disease or high cholesterol levels are a risk factor for the disease or high cholesterol levels are not
related to the disease. So to paraphrase what I'm four-year-old daughter's favorite movie character these
days, Glinda the Good Witch from the Wizard of Oz, we have no idea if cholesterol is a good witch or a bad witch or if HDL
is a good witch or a bad witch when it comes to AMD. So is cholesterol a culprit in AMD?
Genetics say yes because there are many genes that have been associated in cholesterol metabolism that have been
associated with AMD. But there is no clear link between these genes and HDL levels.
For example, some of the mutations in these genes that have been associated with AMD increased the HDL levels, some
of them decreased the HDL levels. So possibly these have independent effects.
And I've shown you that postmortem analogies of AMD eyes there is cholesterol both within the pigment epithelial and
beneath the pigment epithelial cells, but then we don't know, it's a chicken or egg question. We don't know which came first.
Is the presence of cholesterol leading to the disease or is the disease causes the accumulation of cholesterol beneath the
pigment epithelial cells? So we're looking at it from a cell biological perspective, and we're hoping that this will help
us understand whether many drugs that are currently already on the market, like statins -- like the drugs I showed you, the
Pioglitazone and TO, extend cholesterol out of the cell, which are currently used to treat diabetes, cholesterol has
to transfer protein inhibitors, lipase inhibitors, which are used to treat obesity, whether any of these drugs will be
useful in preventing or treating AMD. Now, finally in the last few minutes, I want to focus on what
we can do to actually prevent AMD. Now, all of us know about free radicals and oxidative damage.
Free radicals are metabolites of oxygen that are highly damaging to cells because they can cause damage to DNA proteins, lipids
because they make holes in the cell membrane. And they set off a chain reaction where free radical
damage generates more free radicals which then generate more free radical damages. And antioxidants like
carotenoids lutein and zeaxanthin act as free radical scavengers because they give an extra electron to these
metabolites of oxygen and kind of neutralize them. So they're not only powerful free radical scavengers but in
the eye they filter harmful UV and blue light and prevent it from hitting the retina. So the most important thing that
we can do for our eyes these days is to eat a colorful diet. So eat foods that are green, that are orange, and actually
follow what Michael Pollan says, eat food, not too much, mostly plants. And, of course, there's a study
called the age-related eye disease study, and what it has come up with is that high doses of vitamin A,
vitamin C, vitamin E, zinc, and copper which have been shown to prevent progression of early AMD to late AMD.
So there are these added supplements that one can take now. But then they come with a few
caveats in terms of whether one has been a smoker, then perhaps high doses of vitamin A are not so good because they can
increase the risk of lung cancer. So these are all things that we have to talk with our
ophthalmologist. And then there are even more supplements which have lutein and zeaxanthin which have not
been clinically proven to actually, that study is still going on right now. I think the results are expected
next year. And then there are even more antioxidants that one can take if one so wishes.
So finally what is the take-home message? It is that lifestyle choices can help trump faulty genes.
So if you don't smoke, exercise, exercising has been actually shown to prevent progression of AMD.
In adults over the age of 70, exercising three times a week has been shown to actually decrease the progression of AMD.
Wear sunglasses to protect your eyes from UV radiation. Take antioxidants and eat a healthy diet.
And I'm told that the Obama Administration is coming up with a new food chart. They're doing away with the
pyramid, they're coming up with a plate tomorrow. I was hoping I could find it today and put it on,
but I did the not find it. So these are the preventive things that we can do to actually help our eyes.
And with that, I'd like to thank people in my lab, and part of this work I did as a postdoc at Cornell.
And I have collaborations at UCLA and with other people around the country. Thank you for your attention.
[APPLAUSE]