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Picard Emilie, Alejandra Daruich, quentin lerouzic, Marie-Christine Naud, Laurent Jonet, Laura Kowalczuk, Jean-Antoine Pournaras, Jeffrey H. Boatright, Aurélien Thomas, Natacha Turck, Alexandre Moulin, Francine F Behar-Cohen; Retina transcriptome underlie the neuroprotective actions of transferrin.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5720.
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© ARVO (1962-2015); The Authors (2016-present)
Iron retinal accumulation found in various retinal degeneration diseases like age-related macular degeneration (AMD) or retinal detachment (RD), enhances oxidative-stress mediated photoreceptors cell death. We previously demonstrated the high efficiency of transferrin (TF) to protect against photoreceptors loss, edema and apoptotic/necrotic death in various retinal degeneration models. We performed RNA-seq analysis to reveal the molecular mechanisms involved in TF neuroprotection during RD.
RD was induced on wild-type and transgenic mice expressing human transferrin (TG), by subretinal injection of sodium hyaluronate (n=4). The retinas were collected 4 days later for RNA-sequencing analysis. Comparative transcriptomic analysis was performed and pathway and genes ontology were analyzed
RNA– sequencing analysis identified 412 genes that were differentially modulated (1.5 fold-change, p≤0.05). From those, 149 were up-regulated and 263 were down-regulated in TG retinas compared to WT retinas. Gene ontology analysis revealed that TF expression affected pathways for photoreceptor cell maintenance, immune system, metabolism, cell death mechanisms, neurological process, phagocytosis and tissue remodeling. Among genes differentially regulated, Tfrc (down-regulated) and Igfbp3 (up-regulated) were identified as proteins binding partners of TF, and their proteins expression modifications were confirmed by Western Blot and immunohistochemistry.
Our data suggest the neuroprotective role of TF is the result of interaction in multiple pathways and/or direct interaction with proteins. The role of iron sequestration remains to be determined.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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