Blast preconditioning protects retinal ganglion cells and reveals targets for prevention of neurodegeneration following blast-mediated TBI

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. 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).

研究目的：本研究旨在探讨爆炸预处理对视网膜神经节细胞（retinal ganglion cells，RGC）结构与功能的影响，并明确参与视网膜神经节细胞丢失的分子通路。实验方法：为探究爆炸预处理的干预效果，本研究设置三组小鼠开展实验：① 先接受假损伤操作，于一周后单次暴露于20磅力每平方英寸（PSI）的爆炸损伤；② 先后两次接受低强度爆炸预处理暴露，两次暴露间隔一周，强度均为5 PSI；③ 先接受5 PSI的预处理损伤，一周后再单次暴露于20 PSI的爆炸损伤。本研究采用RNA测序（RNAseq）分析各组间的转录组变化。研究结论：爆炸预处理可对视网膜神经节细胞起到保护作用，使其免受爆炸损伤。该保护效应似乎与犬尿氨酸-3-单加氧酶活性的改变相关，而抑制该酶的活性同样可发挥保护效果。本研究共生成24份视网膜mRNA测序样本，所有样本均分为3组，每组设置三次生物学重复，最终生物学重复数为n=8。实验小鼠接受了不同强度的冲击波压力暴露，具体分组如下：组1：预处理组（先5 PSI，后20 PSI）；组2：单纯爆炸损伤组（先0 PSI，后20 PSI）；组3：假损伤组（先5 PSI，后5 PSI）。