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Raela Ridley, Erin Walsh, Brianna Bowman Young, Ahmed Jafri, Alfred S Lewin, Cristhian J Ildefonso; Acute Subclinical Systemic Inflammation Activates Neuroprotective Mechanisms In Degenerating Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1376.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal inflammation is part of multiple retinal degenerative diseases like age-related macular degeneration (AMD). Recent findings indicate that changes in the intestinal and oral microbiomes can have great impact on the retina health. Therefore, a better understanding of the interaction between the systemic immunity and the retina is needed. To further our knowledge on such interaction, we studied the retinal effects of systemically delivering a low dose of LPS in a mouse model of geographic atrophy.
Mice of the Sod2floxed:VMD2Cre+ genotype between 8-10 weeks of age were injected subcutaneously at the tail base with either saline or 3 mg/kg of LPS (S. typhimurium). We evaluated mice monthly for 3 months by electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). Changes in gene expression were quantified by RT-qPCR, and cytokine changes in serum and retinas were measured by multiplex ELISA. Immune cells in retinal cell suspension were studied by flow cytometry.
Mice injected with LPS had increased a- and b-wave amplitudes together with thicker ONL when compared with saline treated mice. LPS treated mice had increased granulocyte colony stimulating factor (G-CSF) serum concentration 3 days post-injection followed by an increased leukemia inhibitory factor (LIF) retinal concentration 4 days later when compared to saline treatment. Furthermore, LPS treatment caused a retinal increase in Arg1 and Ppar-y mRNA simultaneously with a decrease in STAT-1 mRNA when compared to saline treatment. Although there was no difference in retinal CD45+ cells between groups, flow cytometry experiments showed a decrease in CX3CR1+MHC-II+ cells in LPS treated mice.
We hypothesize that the increase in G-CSF and LIF are responsible for the protection of retinal function and structure in the RPE-specific Sod2 KO mice after LPS treatment. Because G-CSF is currently FDA-approved (e.g. Lenograstim, Neupogen, and Neulasta) for use in non-ocular conditions, our future studies will aim to elucidate the cellular and molecular mechanism of systemic G-CSF on retinal degeneration.
This is a 2020 ARVO Annual Meeting abstract.
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