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Emily Okoren, Rose Mathew, Daniel R Saban; Microglia and monocyte-derived macrophage responses to light damage differ across mouse strains. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Non-redundant functions between resident microglia and recruited monocyte-derived macrophages (mo-MFs) in neuroinflammation are ill-defined, even though it is now firmly established that these are distinct myeloid populations. We have recently reported that the microglia phenotype of CD45lo CD11clo I-A/Elo F4/80lo is conserved in retinal inflammation, whereas acutely recruited mo-MFs are CD45hi CD11chi I-A/Ehi F4/80hi, which we validated using in vivo fate-mapping. Here, we took advantage of this approach to determine their respective responses in light-induced retinal degeneration. We used mouse strains, C57Bl/6J (pigmented), BALB/c (albino), and their F1 progeny, CB6F1J (pigmented), as the latter two harbor increased light susceptibility due to RPE65 genetic variation.
Dark-adapted mice were exposed to white-light LEDs for 4 hr at 40k lux or 8hr at 60k lux on day 0. Mice were then returned to normal housing with normal 12 hr light cycles until euthanasia on day 5. Neuroretinas were harvested for 10-color flow cytometry, which included: viability, CD45 (APC), CD45 (APC-cy7), CD11b, CD11c, I-A/E, Ly6G, Ly6C, F4/80, CD64. Contralateral eye were cryosectioned to assess ONL thinning (DAPI) and immunofluorescence (CD11b, Iba-1).
LED-induced light damage in B6J mice required a 60k lux /8 hr exposure, whereas only 40k lux/4 hr was required in BALB/c and CB6F1J mice. CB6F1J appeared to have greater ONL thinning relative to their BALB/c counterparts. Transmigration of Iba-1+ cells to the photoreceptor layers was readily detectable in damaged CB6F1J mice, whereas transmigration was unremarkable in BALB/c counterparts. Likewise in CB6F1J mice, presence of mo-MF recruits was robust, whereas only microglia were detectable in BALB/c counterparts.
Our findings may suggest that augmented photoreceptor degeneration in CB6F1J could be associated with mo-MF recruitment. These data may therefore implicate mo-MFs in secondary damage that results in greater photoreceptor loss.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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