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 co unteract ischemic or cytotoxic injury to neurons. We investigated whether A TA has a neuroprotective effect on axotomised, 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 RG C 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 af ter axotomy rescued 58% of RCC. However, injection of ATA 4 days after axot omy did not influence the survival of RGC, indicating that crucial, irrever sible cascades of death are initiated prior to this point in time. The TUNE L technique was used to visualise apoptotic ganglion cells and revealed tha t 4 days after axotomy their number was significantly less in retinas whose optic nerves were axotomised 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 gra ft than control RGC. This number could be increased by a second injection o f ATA 7 days after axotomy. These data show that ATA is not only able to de lay post-traumatic neuronal death but also enhances the extent of axonal re generation in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.