Aurintricarboxylic acid promotes survival and regeneration of axotomised retinal ganglion cells in vivo.

Aurintricarboxylic acid (ATA) has been used as an anti-apoptotic drug to counteract ischemic or cytotoxic injury to neurons. We investigated whether ATA has a neuroprotective effect on axotomized, adult retinal ganglion cells (RGC) as a model for traumatic neuronal cell death. A solution of ATA was injected into the vitreous body of rat eyes whose optic nerves had been cut. In controls, 14% of RGC survived 14 days after axotomy, whereas 44% of RGC survived after a single injection of ATA solution, and 59% survived when the injection was repeated after 7 days. A single injection of ATA 1 day after axotomy rescued 58% of RGC. However, injection of ATA 4 days after axotomy did not influence the survival of RGC, indicating that crucial, irreversible cascades of death are initiated prior to this point in time. The TUNEL technique was used to visualise apoptotic ganglion cells and revealed that 4 days after axotomy their number was significantly less in retinas whose optic nerves were axotomized and treated with ATA, than those of controls. As a consequence of neuroprotection, more RGC were recruited to regenerate into a peripheral nerve graft used to replace the cut optic nerve. In this paradigm, ATA-treated RGC extended significantly more axons within the graft than control RGC. This number could be increased by a second injection of ATA 7 days after axotomy. These data show that ATA is not only able to delay post-traumatic neuronal death but also enhances the extent of axonal regeneration in vivo.