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SILENCING$BETA2$ADRENERGIC$RECEPTORS…$$

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a
b L
CB

IR CO IR CO

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Figure. 4.7. Lack! of! changes! in! the! ocular! anatomy! after! the! treatment! with! the! siRNA! against! the!
beta2! adrenergic! receptor.! a)! Control! eye! of! an! untreated! animal! showing! the! main! parts! of!
anterior! and! posterior! chamber.! b)! siRNA! treated! eye! obtained! after! completing! the! whole!
experimental!time.!CO:!cornea,!IR:!iris,!CB:!ciliary!body,!L:!lens.!

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4.(DISCUSSION(

There! is! an! increasing! interest! in! the! use! of! RNAi! therapeutics! to! treat! a!
wide! range! of! diseases;! particularly! those! caused! by! the! expression! of! mutant!
genes,! including! dominantYnegative! proteins,! overYexpressed! genes! leading! to!
gainYofYfunctions! effects! or! aberrant! splicing! isoforms.! Gene! silencing! by! RNA!
interference!has!been!well!demonstrated!to!efficiently!knockdown!targeted!genes!
in!vitro,!but!few!reports!describe!similar!effects!in!vivo!(6).!One!of!the!first!studies!
published! that! showed! the! downregulation! of! VEGF,! a! stimulatory! factor! in!
choroidal!neovascularization!(7),!by!a!single!intravitreal!injection!in!the!eye!(8)!is!
now! being! tested! in! patients! with! subfoveal! choroidal! neovacularization! due! to!
AMD!in!a!Phase!I!Trial.!siRNA!(SirnaY027)!injected!into!the!vitreous!cavity!diffuses!
throughout!the!eye!and!is!detectable!for!at!least!five!days!after!administration!(9).!

The! eye,! as! a! relatively! isolated! compartment,! seems! as! an! ideal! organ! for!
RNAi! treatment.! RNAi! mechanism! of! action! allows! targeting! of! specific! sequences!
of!single!genes!and!local!delivery!should!limit!the!exposure!to!the!rest!of!the!body,!
reducing!the!dose!of!siRNA!to!be!used!and!minimizing!side!effects!in!other!tissues.!
In! this! sense,! treatment! of! eye! diseases! with! this! technology! seems! to! present!

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