Small GTPase Rit and Traumatic Optic Neuropathy

1.7 million Americans apart from hundreds of our active service members suffer TBI annually. A large proportion (~ 60%) of people suffering from TBI with non]superficial injuries report visual impairment and may be at a risk of vision loss. The pathophysiology of TBI induced traumatic optic neuropathy (TON) is unknown. Therefore, the understanding pathophysiology of TON and development of therapies that can promote neuronal survival and communication within retina are very important to the healthcare. Our pilot data suggests that Ras related small GTPase Rit is down regulated in retina following moderate TBI. Rit deficiency in primary RGCs, aggravates excitotoxicity meditated cell death, axonal degeneration and loss of synopses. To validate this discovery, we developed a novel transgenic mouse model that permits neurons specific Rit activation to test whether Rit supplementation in TBI affords protection against TON. Interestingly, neuronal Rit activation in during TBI protects retinal neurons from cell death and axonal degeneration. In retina neuron specific Rit activation leads to activation of the neuroprotective CREB signaling. Based on these we plan to test neuronal RIT activation against RGC degeneration and functional vision impairment after TON. Our hypothesis is that that loss of Rit during TBI might perturb CREB mediated essential neuroprotective signaling in retinal neurons. Hence we propose that therapeutic Rit activation might be a new avenue in the treatment of TON.