Abstract: Corneal infection with Pseudomonas aeruginosa perforates the cornea in C57BL/6 (B6), but not BALB/c mice. Comparative analysis of these two responses has revealed that B6 mice, type 1-dominant responders, exhibit increased inflammation, leading to an exacerbated disease response when compared to BALB/c mice, which demonstrate a less severe/resistant response and are classified as type 2-dominant. Further evidence indicates that SPM circuits, which are differentially activated between the two strains, are essential for host defense during bacterial keratitis. Using this archetype as a model to study inflammation and its regulation, we questioned whether this paradigm could be exploited to expose the events of chronic retinal inflammation associated with the progression of diabetic retinopathy. We further examine the influence of genetic innate immune background and investigate factors that may confer susceptibility to hyperglycemia-induced retinal damage in diabetics using a combination of in vivo and in vitro approaches.