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SILENCING$BETA2$ADRENERGIC$RECEPTORS…$$

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factor( desencadenante( del( glaucoma.( El( empleo( de( un( siRNA( de( origen( comercial(
para(el(receptor(beta2(ha(producido(una(reducción(sustancial(de(la(PIO(de(30(±(5(%,(
comparado(con(el(control,(un(siRNA(sin(sentido((scramble).(Estos(resultados(fueron(
en( magnitud( semejantes( al( de( los( fármacos( comerciales( salvo( que( la( duración( del(
siRNA( para( el( receptor( beta2( adrenérgico( duró( casi( 5( días( en( comparación( de( las( 8(
horas( que( suelen( durar( los( fármacos( comerciales.( Los( estudios( en( relación( con( los(
efectos(secundarios(no(mostraron(ninguna(modificación(en(las(estructuras(oculares.(
En( resumen,( el( empleo( de( los( siRNA( frente( a( los( receptores( beta2( adrenérgicos(
presenta( muy( buenas( perspectivas( como( aproximación( novedosa( para( el(
tratamiento(del(glaucoma.((

Palabras.clave:!Glaucoma;!Presión!intraocular;!Receptores!adrenérgicos;!siRNA.!

1.(INTRODUCTION(
The! aqueous! humour! is! a! transparent! nutritional! fluid! that! provides! the!

nutrients! to! the! inner! avascular! structures! of! the! eye! (1).! This! fluid! also! gives! an!
internal!pressure,!termed!intraocular!pressure!or!IOP!that!grants!the!right!shape!of!
the! ocular! globe.! The! maintenance! of! an! adequate! balance! between! the! formation!
and!the!drainage!of!the!aqueous!humour!is!a!guarantee!of!ocular!health!(2).!When!
changes! in! the! aqueous! humour! dynamics! occur! concomitant! alterations! happen!
that! may! lead! in! pathological! states.! One! problem! derived! from! the! accumulation!
of! the! aqueous! humour! in! the! eye! is! the! degeneration! of! the! optic! nerve! as! a!
consequence! of! the! increase! in! the! intraocular! pressure! (3).! This!
pathophysiological!condition!is!generally!termed!as!glaucoma!and!is!in!most!of!the!
cases! due! to! problems! in! the! drainage! of! the! aqueous! humour! rather! than! a!
problem!in!its!synthesis.!!

The! control! of! the! aqueous! humour! production! occurs! in! the! ciliary! body!
and!it!is!regulated!by!the!sympathetic!nervous!system!(4).!Noradrenaline!released!
from! the! sympathetic! terminals! stimulate! adrenergic! receptors! that! facilitate! the!
production!of!the!aqueous!humour.!This!fact!has!been!taken!by!the!pharmaceutical!
companies!to!develop!a!series!of!antagonists!of!mainly!ß2Yadrenoceptors!although!
a1!agonists!seem!to!help!to!reduce!aqueous!humour!synthesis!(4).!

Recently,! a! new! biochemical! approach! to! avoid! the! expression! of! proteins!
has! been! discovered:! ! Small! interference! RNA.! These! are! double! stranded! RNA!
sequences! that! after! being! processed! in! the! cytoplasm! they! destroy! the! mRNA! to!
which! it! has! been! designed! avoiding! the! synthesis! of! the! corresponding! protein!
(5).!

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