Harper Matthew M, Gramlich Oliver W, Elwood Benjamin W, Boehme Nickolas A, Dutca Laura M, Kuehn Markus H
Departments of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA, USA; Departments of Biology, And Pharmacology, The University of Iowa, Iowa City, IA, USA; Veterans Administration Center for the Prevention and Treatment of Visual Loss, Iowa City VA Healthcare System, Iowa City, IA, USA.
Departments of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA, USA; Departments of Neuroscience and Pharmacology, The University of Iowa, Iowa City, IA, USA; Veterans Administration Center for the Prevention and Treatment of Visual Loss, Iowa City VA Healthcare System, Iowa City, IA, USA.
Exp Eye Res. 2022 Dec;225:109272. doi: 10.1016/j.exer.2022.109272. Epub 2022 Oct 6.
The purpose of this study was to examine the role of the immune system and its influence on chronic retinal ganglion cell (RGC) dysfunction following blast-mediated traumatic brain injury (bTBI).
C57BL/6J and B6.129S7-Rag1/J (Rag) mice were exposed to one blast injury of 140 kPa. A separate cohort of C57BL/6J mice was exposed to sham-blast. Four weeks following bTBI mice were euthanized, and splenocytes were collected. Adoptive transfer (AT) of splenocytes into naïve C57BL/6J recipient mice was accomplished via tail vein injection. Three groups of mice were analyzed: those receiving AT of splenocytes from C57BL/6J mice exposed to blast (AT-TBI), those receiving AT of splenocytes from C57BL/6J mice exposed to sham (AT-Sham), and those receiving AT of splenocytes from Rag mice exposed to blast (AT-Rag). The visual function of recipient mice was analyzed with the pattern electroretinogram (PERG), and the optomotor response (OMR). The structure of the retina was evaluated using optical coherence tomography (OCT), and histologically using BRN3A-antibody staining.
Analysis of the PERG showed a decreased amplitude two months post-AT that persisted for the duration of the study in AT-TBI mice. We also observed a significant decrease in the retinal thickness of AT-TBI mice two months post-AT compared to sham, but not at four or six months post-AT. The OMR response was significantly decreased in AT-TBI mice 5- and 6-months post-AT. BRN3A staining showed a loss of RGCs in AT-TBI and AT-Rag mice.
These results suggest that the immune system contributes to chronic RGC dysfunction following bTBI.
本研究旨在探讨免疫系统在爆炸介导的创伤性脑损伤（bTBI）后慢性视网膜神经节细胞（RGC）功能障碍中的作用及其影响。
将C57BL/6J和B6.129S7-Rag1/J（Rag）小鼠暴露于140 kPa的单次爆炸损伤。另一组C57BL/6J小鼠接受假爆炸处理。bTBI后四周对小鼠实施安乐死并收集脾细胞。通过尾静脉注射将脾细胞过继转移（AT）到未经处理的C57BL/6J受体小鼠体内。分析三组小鼠：接受来自爆炸暴露的C57BL/6J小鼠脾细胞AT的小鼠（AT-TBI）、接受来自假爆炸暴露的C57BL/6J小鼠脾细胞AT的小鼠（AT-Sham）以及接受来自爆炸暴露的Rag小鼠脾细胞AT的小鼠（AT-Rag）。使用图形视网膜电图（PERG）和视动反应（OMR）分析受体小鼠的视觉功能。使用光学相干断层扫描（OCT）评估视网膜结构，并使用BRN3A抗体染色进行组织学评估。
PERG分析显示，AT-TBI小鼠在AT后两个月时振幅降低，并在研究期间持续存在。我们还观察到，与假手术组相比，AT-TBI小鼠在AT后两个月时视网膜厚度显著降低，但在AT后四个月和六个月时未出现这种情况。AT-TBI小鼠在AT后5个月和6个月时OMR反应显著降低。BRN3A染色显示AT-TBI和AT-Rag小鼠中RGCs丢失。
这些结果表明，免疫系统在bTBI后慢性RGC功能障碍中起作用。
