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Haoshen Shi, Jena J Steinle, Elizabeth A Berger; Retinal ischemia reperfusion injury model: a contrast in pathogenic responses between C57BL/6J versus BALB/cJ mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1209.
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Retinal ischemia has been shown to contribute to the pathogenesis observed during diabetic retinopathy (DR). As a result, the retinal ischemia reperfusion (I/R) injury model has been useful in studying neuronal and vascular damage to the retina – damage that is similarly observed during the development of DR. Notably, murine models of both I/R and DR tend to be carried out in C57BL/6J (B6) mice, which have been classified as type 1-dominant responders. In bacterial keratitis models, studies have established that B6 mice are susceptible, while BALB/c mice (classified as type 2-dominant) exhibit a resistant phenotype. Although the cornea and retina are quite different, we questioned whether the type 1/type 2 paradigm could be extrapolated to events associated with the pathogenesis of I/R and related DR.
I/R injury was induced in both B6 and BALB/c mice by cannulating the anterior chamber of one eye of anesthetized animals. The other eye served as control. After 2 days, retinas were collected and stained by hematoxylin and eosin (H/E) to examine neuronal differences. After 10 days, retinal microvasculature was isolated from whole retinas to quantitate differences in degenerated capillaries. Retinal lysates were also processed for protein analyses of key inflammatory mediators known to play a role in the development of DR.
Overall, strain specific differences were observed between B6 and BALB/c mice in response to I/R injury. Retinal thickness of B6 mice was more reduced with fewer retinal cells compared to BALB/c mice at 2 days after injury. In addition, signs of vascular damage were more severe in B6 versus BALB/c retinas at 10 days following injury. Although BALB/c retinas had an increase in acellular capillaries following injury, significantly more degenerate capillaries were quantitated in B6 animals. The less severe response observed in BALB/c mice was further accompanied by significant decreases in inflammatory mediators, such as VEGF.
These data suggest that B6 and BALB/c mice respond to I/R injury differently, which has implications not just for retinal ischemia, but for the development of DR, as well. Elucidating these differences both offers potential therapeutic points of intervention and impacts the current modeling system used to study retinal diseases, such as DR.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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