Transcriptomic and Histological Analysis of Exacerbated Immune Response in Multidrug-Resistant Pseudomonas aeruginosa in a Murine Model of Endophthalmitis

Multidrug-resistant (MDR) endophthalmitis is a serious threat to the whole spectrum of therapeutic procedures associated with the risk of managing and preventing vision loss. We have earlier shown the interplay of immune mediators in patients with MDR (PA) endophthalmitis leading to worse outcome. Expanding on these findings, a murine model of endophthalmitis was developed to explore the effects of drug resistance on the pathogenesis by analyzing the temporal changes in retinal morphology along with its transcriptomic signatures. Clinical isolates of susceptible ( ) and multidrug-resistant PA ( ) were injected intravitreally in C57BL/6 mice followed by enucleation at 6 and 24 h time points postinfection. Disease progression and retinal changes were monitored by clinical and histological assessment and transcriptome analysis in a pair-wise manner. Histological assessment of eyeball revealed higher disease severity ( < 0.05), CD45+ cells ( = 0.007), MPO+ cells ( = 0.01), GFAP+ ( = 0.02), along with higher retinal cell death in mice infected with ( = 0.008). Temporal transcriptome analysis revealed differential expression of nearly 923 genes at 6 h p.i. and 2,220 genes at 24 h p.i. (FC ≥2, adjusted -value