Purpose: The purpose of this study was to examine the effect blast preconditioning on the structure and function of retinal ganglion cells (RGC), and to identify molecular pathways that contribute to RGC loss. Methods: To examine the effect of blast-preconditioning three groups of mice were analyzed, including those 1) subjected to sham injury followed by one single 20 PSI injury one week later, 2) mice exposed to two low intensity preconditioning blast exposures separated by one week (5 PSI, 5 PSI) and 3) mice exposed to a preconditioning injury (5 PSI) followed by a single 20 PSI blast exposure one week later. RNAseq analysis was used to identify transcriptional changes between groups. Conclusions: Preconditioning protects RGC from blast injury. Protective effects appear to involve changes in kynurenine-3-monooxygenase activity, whose inhibition is also protective. Overall design: Retinal mRNA profiles were generated in triplicate for each of the 24 total samples (split into 3 groups), resulting in biological n=8. Mice were subjected to various blast wave pressures. Group 1: preconditioned (5 PSI then 20 PSI). Group 2: blast (0 PSI then 20 PSI). Group 3: sham (5 PSI then 5 PSI).