Joshua Chu-Tan: The science of preserving sight | TED

Transcriber:

Translator: Paola Costa Reviewer: Servizo de Normalización Lingüística

Now to start off today, I want everyone in here to close their eyes

Para comezar, quero que todos os presentes pechedes os ollos

and think about the first thing you saw this morning when you opened your eyes.

e pensedes no primeiro que vistes pola mañá cando abristes os ollos.

You know, was it that stain on your ceiling

Foi, quizais, esa mancha do teito que non dades limpado?

that you keep putting off cleaning?

Was it your partner’s face or your child jumping on top of you?

Foi a cara da vosa parella ou a vosa criatura saltándovos enriba?

Or was it the morning rays of the sun just creeping in through the blinds,

Ou foron os raios de sol do amencer abrindo paso entre as persianas,

that mixture of pink, orange and yellow that signifies the start of a new day.

esa mestura de rosa, laranxa e amarelo que marca o comezo do día?

Keep your eyes shut just for a moment longer.

Mantede os ollos pechados un pouco máis.

And imagine waking up now, but instead of those beautiful images,

Imaxinade que espertades, mais, no canto desas fermosas imaxes,

all you could see is what you're seeing right now.

o único que podedes ver é o que estades vendo agora mesmo.

Darkness.

Escuridade.

Those thoughts, those images of the first thing you saw this morning

Eses pensamentos, esas imaxes do primeiro que vistes esta mañá

being exactly what it is now,

son exactamente o mesmo que agora:

just a memory,

só unha lembranza,

an image conjured by your brain from your past.

unha imaxe do voso pasado deseñada polo voso cerebro.

Now open your eyes.

Agora, abride os ollos.

When I asked people what the one sense that they couldn't live without is

Cando lle preguntaba á xente con que sentido non poderían vivir,

most people immediately say, their sight.

a maioría apuraba a dicir que a vista.

And you can understand why that is.

E podedes comprender o porqué.

I mean, our vision and what we see

É dicir, a nosa visión e o que vemos

play such an integral role in how we perceive the world around us.

son esenciais na nosa percepción do mundo que nos rodea.

Just look at how much we spend on buildings,

Fixádevos canto gastamos en edificios,

on parks, on architecture, on things just to please our visual sense.

parques ou arquitectura, simplemente por satisfacer o noso pracer visual.

But what if we can't see?

E se non podemos ver?

What if we lose this gift?

E se perdemos ese don?

What if slowly but surely,

E se, paseniño,

your visual field looks something like this?

o voso campo visual semella algo así?

Well, this is exactly what happens

Ben, isto é exactamente o que pasa

in age-related macular degeneration, or AMD.

na dexeneración macular asociada á idade ou AMD, en inglés.

This disease is the leading cause of blindness in the developed world.

Esta doenza é a primeira causa de cegueira no mundo desenvolvido.

This disease affects one in seven New Zealanders over the age of 50,

Afecta a un de cada sete neozelandeses de máis de 50 anos

and yet the most common form of this disease has no cure.

e, aínda así, a forma máis común desta doenza non ten cura.

AMD is a serious problem.

A AMD é un problema grave,

But we think we have something that may just be the solution

pero cremos que demos con algo que podería ser a solución

because of tiny molecules called microRNA

grazas a unhas moleculiñas, chamadas microARN,

that are incredibly powerful gene regulators.

que son reguladores xenéticos incriblemente poderosos.

But first, let's talk a little bit about how we actually see.

Antes de nada, falemos un chisco de como vemos en realidade.

Now that is just a stunning structure, isn't it?

É unha estrutura impresionante, non si?

I could stare at it forever,

Podería mirala toda a vida,

which is ironic because that's what allows me to do so.

algo curioso, porque é o que me permite facelo.

This is a retina.

Isto é unha retina.

This is the thing that allows us to absorb light bouncing off of objects.

É o que nos permite absorber a luz que rebota nos obxectos.

This is the thing that allows us to define shapes, define edges.

É o que nos permite definir formas e contornos.

This is what allows us to see.

Isto é o que nos permite ver.

It lines the back of the eye and is multilayered,

Envolve o revés do ollo e ten varias capas.

with each layer containing cells with its own respective role.

Cada unha delas contén células coas súas respectivas tarefas.

Now the cell type I want you to know about today are photoreceptors.

Ora ben, as células das que vos quero falar son os fotorreceptores.

And if you break down the word and figure out what they mean,

Se dividimos a palabra e vemos que significa,

photo, meaning light, and receptors, or something that receives.

temos “foto”, que é “luz”, e “receptores”, algo que recibe.

So they receive the light.

Así que reciben luz.

So when the light comes into our eye,

Así, cando a luz entra nos nosos ollos,

it's received by these cells

estas células recíbena

and through a series of processes

e, a través dunha serie de procesos,

begins to convert it into an electrical signal

empezan a convertela nun sinal eléctrico

that has been sent to the brain.

que se envía ao cerebro.

Eventually, this will form an image.

Finalmente, isto formará unha imaxe.

This is the first step to our vision,

Este é o primeiro paso da nosa visión,

to everything we see, to you looking at me right now.

de todo o que vemos, do feito de que me esteades vendo agora mesmo.

Now there's a specialized region within the retina known as the macula.

Hai unha rexión especializada dentro da retina que se chama mácula.

It's approximately 5 millimeters in diameter

Ten un diámetro de aproximadamente 5 mm

and houses another even more specialized region known as the fovea.

e abeira outra rexión, aínda máis especializada, chamada fóvea.

Now when the light comes into our eye,

Cando a luz penetra no ollo,

it's concentrated to focus on this region of the retina.

concéntrase para focalizarse nesta rexión da retina.

It's responsible for pretty much all of our useful day to day vision,

É a responsable de practicamente toda a nosa visión útil do día a día,

from our color perception

dende a percepción da cor

to our high visual detail, to our central vision.

ata a visión altamente detallada e a visión central.

All of this mediated by this tiny region.

Todo isto grazas a esta pequena rexión.

This is also the region where your photoreceptors begin to die

Tamén é a rexión onde os fotorreceptores comezan a morrer

if you have AMD.

se tes AMD.

In fact, a 1.5-millimeter lesion in this area,

Unha lesión de 1,5 mm nesta área,

which is approximately the thickness of a credit card,

que vén sendo do grosor dunha tarxeta de crédito,

will render you legally blind.

pode deixarte legalmente cego.

Unfortunately, AMD is an incredibly complex disease,

Por desgraza, a AMD é unha doenza enormemente complexa,

and what this means is if you try and block a single thing

o que significa que se intentas evitar unha das causas

leading to the disease,

que producen a doenza,

it's very likely that something else would just come and take its place.

é moi probable que apareza outra causa para substituíla,

Whether that be well establish causes, such as inflammation or oxidative stress,

ben por orixe coñecida, como a inflamación ou o estrés oxidativo,

or things we just don't even know about yet.

ou por algo do que aínda non sabemos.

It's the same issue that faces researchers looking into treatments

Os investigadores afrontan o mesmo problema procurando tratamentos

for all kinds of neurodegenerative diseases,

para enfermidades neurodexenerativas

such as Alzheimer's or Parkinson's.

como o alzhéimer ou o párkinson.

But what if we could find one therapy that could treat multiple causes?

E se puidésemos atopar unha terapia para tratar varias causas?

You know, what if we could get to the root of the disease?

Quero dicir, e se puidésemos chegar ata a raíz da doenza?

Well, maybe we can, but to get there,

Igual podemos, mais, para chegar aló,

we need to understand just a little bit about genetics.

cómpre entender algo sobre xenética.

Now some of you may be familiar with the famous Watson, Crick and Wilkins,

A algúns igual vos soan os famosos Watson, Crick e Wilkins,

who in many ways were the pioneers of DNA as we know it.

que foron, de moitas formas, os pioneiros do ADN tal e como o coñecemos.

I'm sure a lot of you will also be familiar

Estou seguro de que tamén vos soa

with Steven Spielberg's epic movie "Jurassic Park."

o gran filme de Steven Spielberg, Parque Xurásico.

Remember that scene

Lembrades aquela escena

where they have a preserved mosquito with dinosaur’s blood in it,

na que conservaban un mosquito con sangue de dinosauro dentro,

and they use that to create new dinosaurs

e o empregaban para crear novos dinosauros

and probably the coolest yet most dangerous theme park of all time.

e probablemente o parque de atraccións máis xenial e perigoso da historia?

Well, a lot of you probably scoffed at that idea,

Seguro que moitos escachastes de risa coa idea, mais,

but in some ways, genetically speaking, it's actually true.

dalgún xeito, en termos xenéticos, están no certo.

As Francis Crick said, DNA makes RNA,

Como dixo Francis Crick, o ADN crea ARN,

RNA makes protein, and protein makes us.

o ARN crea proteína e a proteína créanos a nós.

This is the central dogma of genetics.

É o dogma central da xenética.

You can think of DNA as the code,

Podedes imaxinar o ADN coma un código

coding for just about everything about us,

que nos codifica basicamente por completo

so it makes us human and not a monkey, a rat or a dog.

para sermos humanos e non un mono, un rato ou un can.

So it makes us unique individuals.

Para sermos individuos únicos.

It's what makes us who we are,

É o que fai que sexamos nós,

but it is just the code.

mais é só un código.

So without the other components of this central dogma,

Entón, sen os demais compoñentes deste dogma central,

it's just going to sit there like a book waiting to be read.

vai quedar aí sentado coma un libro esperando a que o lean.

Knowledge from this book just waiting to be implemented.

O saber dun libro que espera para implantarse.

Now your RNA are your messengers responsible for bringing some of that code

O ARN é o mensaxeiro responsable da entrega de parte dese código

and telling our cells,

e de dicirlles ás células:

OK, this is what needs to be produced right now.

“Isto é o que temos que producir.”

Then the protein that's made is your functional component,

Entón, a proteína creada é o noso compoñente funcional

or your workers, if you will.

ou os nosos traballadores.

You can actually think of this central dogma

Podedes imaxinar este dogma central

as Swedish flatpack furniture giant IKEA.

coma o IKEA, o xigante sueco de mobles para ensamblar.

Think of the IKEA warehouse as your DNA,

Imaxinade que unha tenda de IKEA é o voso ADN;

containing all of the code,

contén todo o código,

all the instructions for how these pieces of furniture will be made,

todas as instrucións de montaxe dos mobles,

but nothing is actually assembled yet.

pero aínda non hai nada montado.

You choose what you need and you come out of the warehouse

Podedes escoller o que precisades e saír da tenda

with a set of instructions for your furniture.

cunha serie de instrucións para os mobles.

The set of instructions is your RNA, copies and copies of these instructions,

Estas instrucións son o voso ARN, exemplares e exemplares de instrucións

leaving the warehouse, telling us exactly how we assemble these pieces of furniture.

que saen da tenda e nos din exactamente como montarmos os mobles.

Then the fully functional furniture, whether it be your wardrobe or a couch,

Logo, a peza completamente funcional, sexa o voso armario ou un sofá,

that's your protein, all assembled, ready to do what they need to do.

é a vosa proteína, totalmente ensamblada e lista para facer o que precisa.

DNA makes RNA, RNA makes protein, and protein makes us.

O ADN crea ARN, o ARN crea proteína e a proteína créanos a nós.

Now when we talk about a standard gene therapy,

Ao falarmos dunha terapia xénica estándar

you're often looking at a single target.

adoitamos fixármonos nun único obxectivo.

So gene therapies are fantastic

As terapias xénicas son marabillosas

for diseases that can be attributed to a single gene mutation

para as doenzas atribuídas a unha única mutación xénica

or single root cause.

ou a unha soa causa principal.

Mais para doenzas como a AMD,

But for a disease like AMD,

where there's multiple possible causes,

onde hai múltiplas causas posibles,

it's just not as useful at this point in time.

xa non é tan útil neste momento.

But there's another type of RNA called microRNA.

Hai outro tipo de ARN que se chama microARN.

And instead of coding for the creation of protein,

No canto de codificar para crear proteína,

these microRNA can actually control which RNA are being read.

este microARN pode controlar que ARN se pode ler.

They are incredibly powerful molecules,

Son moléculas incriblemente potentes:

with a single microRNA having the ability

un só microARN ten a capacidade

to control up to 200 different targets

de controlar até 200 obxectivos distintos

in what is known as negative regulation.

no que se coñece como regulación negativa.

What this means is that when it binds to an RNA,

Isto significa que, cando se adhire a un ARN,

it stops it from being read and the protein from being produced.

deixa de lerse e a proteína deixa de producirse.

So let's go back to IKEA.

Volvamos ao IKEA.

Imagine microRNA as an officer roaming the car park of IKEA,

Imaxinade que o ARN é un vixiante roldando no aparcadoiro do IKEA,

checking everything that's coming out of the warehouse

comprobando todo o que sae da tenda

for a particular type of furniture.

para un tipo concreto de moble.

Now notice I say type.

Fixádevos, digo “tipo”.

This is what I mean by a pathway.

A isto é ao que me refiro cando falo dunha vía.

So let's say we're suffering from a coffee table epidemic

Digamos que sufrimos dunha epidemia de mesas auxiliares

where people are just cluttering their living rooms

e que a xente está amoreando os seus salóns

with coffee tables upon coffee tables upon coffee tables for no apparent reason.

con mesas sobre mesas sen razón ningunha.

Now IKEA will sell hundreds of different kinds of coffee tables,

IKEA venderá centos de tipos distintos de mesas auxiliares,

but they're all still coffee tables serving the same general function.

mais seguen a ser mesas auxiliares que cumpren a mesma función xeral.

A microRNA officer will recognize this

Un vixiante microARN recoñeceríao

and specifically get rid of all coffee table instructions.

e desfaríase especificamente de todas as instrucións das mesas auxiliares.

Doesn't matter the shape, the size or the color.

Tanto ten a forma, o tamaño ou a cor.

If it’s a coffee table, the instructions will no longer be read,

Se é unha mesa auxiliar, non se van ler as súas instrucións

and it will no longer be assembled.

e non se van ensamblar.

This is how microRNA work.

Así é como funcionan os microARN.

They can regulate multiple genes from the same pathway,

Poden regular múltiples xenes da mesma vía

and this is why they are so powerful

e por iso son tan poderosos,

because we now have the ability to control an entire pathway

porque agora temos a capacidade de controlar unha vía enteira

rather than a single gene on it.

e non un único xene.

MicroRNA have only really been discovered since the turn of the century,

Os microARN descubríronse ao comezo do novo século

and yet there are already multiple microRNA-based therapeutics

e xa hai varias terapias baseadas no microARN

and clinical trials for complex diseases such as cancer.

e ensaios clínicos para doenzas complexas coma o cancro.

This shows their potential.

Isto amosa o seu potencial.

This shows their rapidness in going from the lab bench

Isto amosa a súa rapidez de salto dende o mesado do laboratorio

to the clinical bedside.

ata o tratamento ao pé de cama.

So let's recap.

Recapitulemos.

We have an incredibly complex disease known as age-related macular degeneration,

Temos unha doenza incriblemente complexa, a dexeneración macular asociada á idade

or AMD.

ou AMD,

A disease that affects the central vision

unha doenza que afecta a visión central

with the most common form having no known cure or treatment.

e cuxa forma máis común non ten nin cura nin tratamento.

We have DNA, code that makes us us.

Temos o ADN, o código que nos fai ser nós.

We have RNA messengers for the creation of protein,

Temos os ARN mensaxeiros para a creación de proteínas

and then we have microRNA, controllers of this process.

e temos os microARN, controladores deste proceso.

So in order to decide which microRNA might be effective in AMD,

Así que, para decidirmos que microARN podería ser efectivo na AMD

we used a technique that allowed us to figure out

empregamos unha técnica que nos permitiu descubrir

all of the active microRNA in the retina and the targets they're controlling.

todos os microARN activos na retina e os obxectivos que controlan.

Using this technique, we found there’s a particular microRNA

Con esta técnica descubrimos que hai un microARN concreto,

known as microRNA-124,

coñecido como microARN-124,

our hero of the story.

que é o heroe da nosa historia.

124 was far and wide the most abundant and active microRNA

O 124 era, de lonxe, o microARN máis abundante e activo

that we found in the retina.

de toda a retina.

It's definitely playing a role.

Cumpre unha misión, sen dúbida.

In fact, we found that it's playing an anti-inflammatory role.

De feito, descubrimos que é unha misión antiinflamatoria.

This is one of the pathways that it acts on.

Esta é unha das vías nas que actúa.

So it controls the production of highly inflammatory molecules

E controla a produción de moléculas altamente inflamatorias

when the retina gets too stressed.

cando a retina se estresa.

124 is strong.

O 124 é forte.

It's a great worker, helps the greater good.

É un gran traballador, loita polo ben común.

Exactly like a hero should.

Exactamente igual que un heroe.

So we looked in the retinas of AMD patients

Así que miramos nas retinas dos pacientes con AMD

and what we found was this.

e atopamos isto.

124, stained in red,

O 124, tinguido de vermello,

was completely absent from the central retina of AMD patients

estaba completamente ausente na retina central dos pacientes con AMD

compared to a healthy individual.

en comparación cun individuo san.

Completely.

Completamente.

Remember the part of your retina

Lembrades a parte da retina

responsible for pretty much all of our useful vision?

responsable de practicamente toda a nosa visión útil?

Well, 124 is missing there.

Ben, pois falta o 124.

And this is what we think is happening.

E isto é o que cremos que pasa.

124 is the most active microRNA in the retina,

O 124 é o microARN máis activo da retina,

meaning that it's working a lot even in a disease state,

o que implica que traballa moito ata cando existe unha doenza,

fighting off danger molecules,

loita contra moléculas perigosas,

inflammatory molecules that will cause even more harm.

moléculas inflamatorias que causarán aínda máis dano.

Now the retina recognizes this

A retina recoñéceo

and activates more and more of our 124.

e activa máis 124.

However, the retina eventually gets overwhelmed.

Porén, a retina acaba por esgotarse.

Tragically, our heroes can no longer keep fighting

Traxicamente, os nosos heroes non poden loitar máis

and start dying off

e comezan a morrer

to the point where they are completely absent.

ata o punto de que están ausentes por completo.

Exactly like we see in those AMD patients.

Igual que o que vemos nos pacientes con AMD.

The enemies keep coming.

Os inimigos seguen a vir.

124, though, no more, missing in action.

Pero xa non hai máis 124 en combate.

And as a consequence, our retina suffers.

En consecuencia, a nosa retina sofre.

Our vision suffers.

A nosa visión sofre.

So in a study we published last year,

Nun estudo que publicamos o ano pasado

we supplemented 124 to animals that have undergone retinal damage.

suplementámoslles 124 a animais que padecían de dano retinal.

And through an injection of these molecules into the eye,

A través dunha inxección destas moléculas no ollo,

what we saw was that animals receiving the treatment

vimos que os animais que recibían o tratamento

had better retinal function,

tiñan unha mellor función retinal,

had less photoreceptor cell death

menos morte de células fotorreceptoras

and had less inflammation.

e menos inflamación.

These are preliminary experiments but a very promising start at that.

Estes son experimentos preliminares, mais cun comezo moi prometedor.

Our next step is to carefully analyze all of the targets

O seguinte paso é analizar minuciosamente todos os obxectivos

that this 124 acts to control.

que controla este 124.

And we're also particularly interested

Tamén temos un interese particular en

in how it is that these microRNA travel in the retina

como viaxan estes microARN pola retina

as a form of communication between cells.

a modo de comunicación celular.

Now what do I mean by this?

A que me refiro con isto?

Well, we mainly focused on photoreceptors,

Ben, centrámonos pricipalmente nos fotorreceptores,

but the retina is an interconnected network,

mais a retina é unha rede interconectada

with every cell contributing to its overall function.

con células que contribúen á función xeral.

In this same study,

Neste mesmo estudo,

we found that 124 moves from the photoreceptor cells

decatámonos de que o 124 se move desde as células fotorreceptoras

to another cell type,

ata outro tipo de células,

but only after the retina is damaged.

mais só despois dun dano na retina.

Too often we kind of look at what's happening in the cells,

Reparamos demasiado a miúdo no que pasa nas células

completely forgetting there's actually a space in between them.

e esquecémonos por completo de que hai un espazo entre elas.

So if we can harness this

Entón, se podemos aproveitar isto

and discover how and why these microRNA move between cells,

e achar como e por que se moven estes microARN entre células,

then we can engineer a deliverable vehicle

poderemos enxeñar un vehículo de distribución

to transport the microRNA that we want exactly where we want it.

para transportar o microARN que queiramos exactamente onde queiramos.

Now I want everyone to have a look at this image again.

Agora quero que miredes outra vez esta imaxe

And imagine living the rest of your life with vision like this.

e que imaxinedes vivir o resto da vosa vida cunha visión coma esta.

So next time you're with your loved ones,

Cando esteades cos vosos seres queridos,

study their faces, their every feature.

estudade as súas caras, cada facción.

Next time you wake up in the morning,

Á próxima que vos ergades pola mañá,

pay attention to every single detail of what you're seeing.

reparade en cada detalle que vexades.

Use that gift of sight

Empregade ese don da vista

and cherish these memories.

e apreciade eses recordos.

Because as I said,

Porque, como xa dixen,

one in seven of you will lose this ability if nothing is done about this disease.

un de cada sete perderá esta capacidade de non facerse nada con esta doenza.

With an aging demographic in current times,

Nun contexto de envellecemento demográfico,

our society seems to be very concerned about living longer

a nosa sociedade semella estar moi concienciada con vivir máis tempo

and extending our lifespan.

e con estender a esperanza de vida.

But this is so wrong.

Pero iso está fatal.

Trust me when I say this.

E fiádevos de min cando digo isto.

Longevity is not the answer.

A lonxevidade non é a resposta.

Quality is the answer.

A calidade si é a resposta.

It's not about --

A cousa non é…

(Applause)

(Aplausos)

It's not about how long we can live, no.

A cousa non é canto podemos vivir, non,

It's about how long we can live well.

senón canto podemos vivir ben.

And with the use of microRNA

E, co uso de microARN,

our hope and our goal is that for millions of people,

a nosa esperanza e o noso obxectivo é que millóns de persoas

this image can become clearer

poidan ver esta imaxe máis clara

for longer.

durante máis tempo.

Thank you.

Grazas.

(Applause)

(Aplausos)