Ocular neuroprotection by siRNA targeting caspase-2

Research output: Contribution to journalArticle


  • H Kalinski
  • Martin Berry
  • M Almasieh
  • H Ashush
  • N Slager
  • A Brafman
  • I Spivak
  • N Prasad
  • I Mett
  • E Shalom
  • E Alpert
  • A Di Polo
  • E Feinstein

Colleges, School and Institutes


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.


Original languageEnglish
Pages (from-to)e173
JournalCell death & disease
Early online date16 Jun 2011
Publication statusPublished - 16 Jun 2011