Temporal Dynamics of Retinal Inflammation Following Blast Exposure in a Ferret Model

Blast-induced traumatic ocular injury (bTOI) is a major cause of vision loss in military personnel involved in recent combat operations. However, its underlying mechanisms remain poorly understood, hindering the development of effective treatments. This study investigated the temporal expression patterns of key inflammatory markers in the retina after blast exposure using a ferret model. Ferrets (<i>n</i> = 40) were subjected to two tightly coupled blasts (20 psi) using an advanced blast simulator. Retinal tissues were collected at 4 h, 24 h, or 28 days post-blast. Differential mRNA expression of Toll-like receptors (<i>TLR</i>s: <i>1-9</i>), cytokines (<i>IL</i>: <i>1β, 6,</i> and <i>10</i>), and cyclooxygenase enzymes (<i>COX</i>: 1 and 2) was assessed using quantitative real-time polymerase chain reaction after blast exposure and compared with sham controls. Our results revealed a rapid and sustained upregulation of multiple <i>TLR</i>s (1, 2, 4, 5, 7, and 8) in the retina following blast exposure, indicating a robust inflammatory response. This was accompanied by a significant increase in pro- and anti-inflammatory cytokines (<i>IL-1β</i>, <i>IL-6 IL-10,</i> and <i>COX2</i>) at 4 h post-blast, suggesting their involvement in the acute pathogenesis of bTOI. Our findings emphasize the critical role of early innate immune responses and the potential for chronic inflammation in bTOI, highlighting the importance of timely therapeutic interventions. Targeting these inflammatory pathways may offer therapeutic avenues for mitigating retinal damage and improving ocular function.