Caspase inhibitors block the retinal ganglion cell death following optic nerve transection

Critical interval of somal calcium transient after neurite transection determines B104 cell survival

“…In adult in vivo models, cell death was more likely following axotomy near the soma of adult rat spinal dorsal root ganglion (Hines and Tessler, 1989), cranial motoneurons (Snider and Thaneder, 1989), retinal ganglion cells (Villegas-Perez, 1993;Kermer et al, 1998;Chaudhary et al, 1999), corticospinal tract neurons (Giehl and Tetzlaff, 1996), and axons of Clarkes' nucleus (Sanner et al, 1993). Similar to the outcome of B104 cells with transected neurites, a percentage (20-50%) of axotomized neurons in vivo survived, but the increased mortality of neurons axotomized near the soma was attributed to the loss of neurotrophic factors delivered by untransected collaterals (of neighboring cells) more proximal to the soma (Berkelaar et al, 1994, Villegas-Perez et al, 1993.…”

“…For example, most axotomized retinal ganglion cells (Villegas-Perez, 1993;Kermer et al, 1998;Chaudhary et al, 1999) survive until 5 days post-axotomy. Many of these cells then died from 5 days to 2 weeks post-axotomy.…”

Administration of brain-derived neurotrophic factor suppresses the expression of heat shock protein 27 in rat retinal ganglion cells following axotomy

“…Activation of caspase-3 is reported to be the crucial step leading to neuronal apoptotic death (Nicholson and Thornberry, 1997) and caspase-9 functions as the upstream activator of caspase-3 . In the retina, inhibition of caspase-3 and caspase-9 activation has significantly improved the survival of RGCs following optic nerve transection (Chaudhary et al, 1999;Garrido et al, 1999;Kermer et al, 1999Kermer et al, , 2000Pandey et al, 2000). Hsp27 may play a direct role in the blockade of caspase activation in the subset of Hsp27-positive RGCs following optic nerve transection and may lead to the long-term protection of this small population of neurons.…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…For example, a knockout of the apoptotic protein Bax in retinal ganglion cells maintains their viability despite severe axonal injury or experimental glaucoma (Isenmann et al 1999;Libby et al 2005). Another example is the use of caspase inhibitors, either via drugs or antisense methods (Kermer et al 1998(Kermer et al , 2000Chaudhary et al 1999;McKinnon et al 2002). A second approach is to go further upstream and block induction of the death pathways, mediated by messengers such as superoxide induction (Kanamori et al 2010a, b;Catrinescu et al 2012), loss of Jun kinase signaling (Harder et al 2011;Fernandes et al 2012), activation of dual leucine zipper kinase signaling Huntwork-Rodriguez et al 2013), beta-amyloid aggregation (Tsuruma et al 2010;Parsons et al 2015), or other intracellular signals.…”