A Contrast in Pathogenic Responses between C57BL/6J and BALB/cJ Mice Using a Model of Retinal Injury

Ischemia is associated with the pathogenesis of retinal disease, including diabetic retinopathy and glaucoma. As a result, the retinal ischemia/reperfusion injury model has been used to study neurovascular changes. Historically, murine models of retinal disease are established in C57BL/6J (B6) mice, which have been described as type 1–dominant responders. In bacterial keratitis models, B6 mice are susceptible, whereas BALB/cJ (BALB/c; type 2–dominant) mice exhibit a resistant phenotype. As such, we questioned whether the type 1/type 2 paradigm could be extrapolated to events associated with retinal pathogenesis. The current study compares the retinal response of B6 with BALB/c mice to investigate strain-specific differences. Retinas were collected at 2 and 10 days after ischemia/reperfusion injury to examine differences in neurovascular degeneration, leukostasis, oxidative stress, glial activation, and select inflammatory mediators. Although both strains showed signs of retinal injury, significantly more damage was observed in B6 mice. Retinal thickness was reduced and vascular damage was more severe in B6 mice. Exacerbated response to injury in B6 versus BALB/c retinas was further supported by increased leukostasis, inflammatory mediators, reactive oxygen species, and lipid peroxidation. In addition, more terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling–positive cells and increased glial activation were detected in B6 mice. These data indicate that B6 and BALB/c retinas differentially respond to injury, which has broader implications regarding the development and study of retinal diseases.