Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling.

ABSTRACT: We have previously shown that crushing the optic nerve induces death of retinal ganglion cells by apoptosis, but suppression of CASP2, which is predominantly activated in retinal ganglion cells, using a stably modified short interfering RNA CASP2, inhibits retinal ganglion cell apoptosis. Here, we report that combined delivery of short interfering CASP2 and inhibition of CASP6 using a dominant negative CASP6 mutant activates astrocytes and Müller cells, increases CNTF levels in the retina and leads to enhanced retinal ganglion cell axon regeneration. In dissociated adult rat mixed retinal cultures, dominant negative CASP6 mutant + short interfering CASP2 treatment also significantly increases GFAP+ glial activation, increases the expression of CNTF in culture, and subsequently increases th

SUBMITTER: Vigneswara V 

PROVIDER: S-EPMC4032097 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature