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Faizah Bhatti, Netsanet Kassa, Johannes Kung, Phillip S Coburn; Effect of Surfactant Protein A on Retinal Cytokines and Microglia in Systemic Inflammation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):807.
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© ARVO (1962-2015); The Authors (2016-present)
Activation of retinal microglia is associated with retinal neovascularization (NV) in the mouse model of oxygen induced retinopathy (OIR) and in the presence of systemic inflammation (SI). SP-A expression is also known to be up regulated in the retinas of wild type (WT) mice after intravitreal injections of toll like receptor (TLR) 2 and 4 ligands. SP-A expression is also increased in NV in WT mice. We hypothesize that retinal SP-A is upregulated in SI and that it also modulates retinal cytokine and microglial expression.
SI was induced in WT mice by intraperitoneal (IP) injection of lipopolysaccharide (LPS) at Day 4. SP-A protein was measured in the retina after 48 and 72 hrs. mRNA of IL-1β, TLR-4, TNFα and a microglial specific marker Iba1 were quantified by real time PCR on P6 and P10 in SP-A-/- mice compared to WT. Total number of microglia were compared between WT and SPA-/- mice on flat mounts (FM) stained with antibody for Iba1.
SP-A protein was significantly increased in WT mice 48 hours after LPS injection (899 ± 93.53 ρg /mg retinal protein) vs controls (374 ± 62.93 ρg /mg retinal protein) but there was no difference at 72 hrs. At P6, VEGF, cytokines and Iba1 were increased in WT vs SP-A-/-. However, at P10, there was an increase in TLR-4, TNFα and Iba1 in SP-A-/- vs WT. VEGF remained high in WT mice at P10 but there was no difference in IL-1β. At P6, the number of total microglia in central and peripheral retinal zones were significantly higher in WT vs SPA-/- mice. At P10, the number of microglia in the central zone of retina were increased in SP-A-/- vs WT mice, but there was no difference in the periphery.
SP-A is up regulated in the neonatal mouse retina in SI. Absence of SP-A is associated with an initial decrease in retinal cytokines 2 days after induction of SI but the cytokines were higher at 6 days. These results suggest that SP-A may play differing roles during the acute and late phase of SI. Furthermore, absence of SP-A was associated with a decrease in microglia on retinal flatmounts 48 hour in SI, suggesting that SP-A may play a role in chemotaxis of microglia. The decreased retinal VEGF expression in SP-A deficient mice also suggests that SP-A may be important in the progression of inflammation leading to vaso-obliteration and NV.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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