Ocular neuroprotection by siRNA targeting caspase-2

被引：122

作者：

Ahmed, Z. ^{[1
,2
]}

Kalinski, H. ^{[3
]}

Berry, M. ^{[2
]}

Almasieh, M. ^{[4
]}

Ashush, H. ^{[3
]}

Slager, N. ^{[3
]}

Brafman, A. ^{[3
]}

Spivak, I. ^{[3
]}

Prasad, N.

Mett, I. ^{[3
]}

Shalom, E. ^{[3
]}

Alpert, E. ^{[3
]}

Di Polo, A. ^{[4
]}

Feinstein, E. ^{[3
]}

Logan, A. ^{[2
]}

机构：

[1] Univ Birmingham, Neuropharmacol & Neurobiol Sect, Sch Clin & Expt Med, Coll Med & Dent Sci,Inst Biomed Res W, Birmingham B15 2TT, W Midlands, England

[2] Neuregenix Ltd, Birmingham, W Midlands, England

[3] Quark Pharmaceut Inc, Div Res, IL-70400 Ness Ziona, Israel

[4] Univ Montreal, Dept Pathol & Cellular Biol, Montreal, PQ, Canada

来源：

CELL DEATH & DISEASE | 2011年 / 2卷

基金：

英国惠康基金;

关键词：

synthetic siRNA; retinal ganglion cells; apoptosis; caspase-2; neuroprotection; RETINAL GANGLION-CELLS; DEATH IN-VIVO; ISCHEMIC OPTIC NEUROPATHY; NEUROTROPHIC FACTOR; INDUCED APOPTOSIS; ADULT-RATS; GENE-THERAPY; DNA-DAMAGE; CPP32-LIKE PROTEASES; INTERFERON RESPONSE;

D O I：

10.1038/cddis.2011.54

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprotective agents for intervention in human diseases involving RGC loss. Cell Death and Disease (2011) 2, e173; doi:10.1038/cddis.2011.54; published online 16 June 2011

引用

页码：e173 / e173

页数：10

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