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Abstract #47124 Published in IGR 13-3
Ocular neuroprotection by siRNA targeting caspase-2
Ahmed Z; Kalinski H; Berry M; Almasieh M; Ashush H; Slager N; Brafman A; Spivak I; Prasad N; Mett ICell Death and Disease 2011; 2: 173
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.
Z. Ahmed. Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
