Identification of immune cell subsets involved in retinal ganglion cell damage following blast exposure

Abstract

Traumatic brain injury from blast exposure (bTBI) has been shown to cause functional and structural retinal ganglion cell (RGC) damage. Previous studies have shown the immune system is activated following blast exposure and that adoptive transfer (AT) of splenocytes from mice exposed to bTBI into healthy naïve mice caused RGC dysfunction and death. In the current study we have extended these findings to identify specific immune cell populations sufficient to induce RGC damage. C57BL/6J mice were exposed to bTBI. One month later either CD19+CD3− B-cells, CD3+ T-cells, CD4+ T-cells, CD8+ T-cells, Dendritic cells (DCs), Natural Killer (NK) cells, or Pan B-cells (B-cells and plasma cells) were isolated from both sham mice as well as mice exposed to bTBI and were subsequently transferred into naïve healthy mice. Functional and structural analysis of the visual system was performed using the pattern electroretinogram (PERG), assessment of visual acuity, and optical coherence tomography imaging, followed by histological analysis at the end of the study. Our results have shown that AT of CD3+ T-cells resulted in PERG deficits coupled with RGC loss. In contrast, CD4+ T-cells, and Pan B-cells induced transient RGC dysfunction, but did not result in RGC loss. Our results have shown that CD3+ T-cells, which include multiple types of T-cells, can induce RGC dysfunction and death, potentially though synergistic interactions among T-cell subtypes. Understanding how T-cells cause visual dysfunction following bTBI may help to develop targeted treatments to interrupt this process.