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Effect of high lipid exposure on retinal glial cell activation

Abstract : Diabetic retinopathy (DR) remains the first cause of visual loss in the age-working population in industrialized countries, and current treatments of the disease are not fully satisfying. Growing evidences indicate that Müller glia cells (MGCs) activation is involved in DR formation and may occur early, even before any vascular changes. Glucose may not be the only factor leading to inflammatory and vascular changes in DR, and recent studies demonstrated the role of dyslipidemia and fatty acids in this disease. We aimed to investigate MGCs inflammatory and angiogenic response to high glucose and high lipid exposure. In this work, we described for the first time the production of Müller cells from reprogrammed induced pluripotent stem iPS (hiMGCs) from different origins, and assayed their response to DR-relevant stress to evaluate their potential use in disease modeling approaches. Using a transcriptomic approach, we showed that unstimulated hiMGCs express 18 key MGCs proteins at similar levels to post-mortem human retina. Similar to primary MGCs, hiMGCs poorly respond to glucose but respond to high lipid exposure by up-regulating their inflammatory and angiogenesis reactions. Finally, we showed that PA stimulated hiMGCs secrete angiogenic factors related to DR such as VEGF, IL-8, IL-1ß and ANGPTL4 and have a pro-angiogenic activity ex-vivo. Taken together, these hiMGCs represent an extremely valuable tool to better understand mechanisms of complex diseases and for the development of new therapeutics. In particular, hiMGCs can be generated from donors and easily expanded to be used in high-throughput drug screens.
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  • HAL Id : tel-02611955, version 1

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Aude Couturier. Effect of high lipid exposure on retinal glial cell activation. Human health and pathology. Sorbonne Université, 2018. English. ⟨NNT : 2018SORUS501⟩. ⟨tel-02611955⟩

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