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 Pseudomonas aeruginosa (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 (S-PA) and multidrug-resistant PA (MDR-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 MDR-PA eyeball revealed higher disease severity (p < 0.05), CD45+ cells (p = 0.007), MPO+ cells (p = 0.01), GFAP+ (p = 0.02), along with higher
retinal cell death in mice infected with MDR-PA (p = 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 p-value <0.05). Pathway enrichment analysis identified differential regulation of
chemokine- and
cytokine-mediated, MAPK, and NF-кβ signaling pathways. In conclusion, rapid deterioration of
retinal architecture and immune exacerbation was significantly associated with the MDR
endophthalmitis, suggesting the need for
immunomodulatory agents to strengthen host cell functions and support
antibiotics to save the
retinal structure from inevitable deterioration and restoration of the vision.