Peripheral inflammatory response to optic nerve injury in adult male mice

Abstract

Record ID: 168

Program Affiliation: Undergraduate Labratory Research

Student Major: Biological Sciences

Project Advisor: Nathan Evanson

Abstract: Approximately 2.5 million people sustain a traumatic brain injury (TBI) annually in the United States. In addition to other deficits, TBIs can lead to vison impairment by ways of indirect or direct eye, nerve, or brain injury. When injury affects the optic nerve, it is termed Traumatic Optic Neuropathy (TON). Studies have found that TON triggers an inflammatory response at the injury site, causing secondary damage to the optic nerve, which leads to axon degeneration and retinal ganglion cell death. However, it is unknown whether injured tissue in the central nervous system would be affected by targeting peripheral immune responses, which are also upregulated after TBI. Thus, we hypothesized that blocking peripheral cytokine signaling would improve degeneration in the optic tract. Using a closed-head, weight-drop TBI model in adult, male C57BL/6 mice, we collected tail blood 6 hours post-TBI to assess inflammatory cytokine levels. 24 hours post-TBI, mice were injected intraperitoneally with anti-IL-6, anti-IL-1β, anti-TNFα, or IgG (vehicle control) monoclonal antibodies.  Tissue was collected seven days post injury for immunofluorescence using Fluoro-Jade B to identify degenerating axons. IL-1β and  IL-6 were significantly increased in injured mice, while TNFα was significantly decreased. But only antiIL6 mice showed less degeneration compared to sham. Overall, it is likely that an “ideal balance” of cytokines needs to be found as reducing IL6 was beneficial, but not TNFα or IL1β. Although we show a relationship between peripheral inflammation and TON, more research is needed to find the perfect balance of cytokine signaling for CNS protection.