July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Dyslipidemia-associated activation of monocyte-derived macrophages in diabetic retinopathy
Author Affiliations & Notes
  • Guillaume Blot
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
  • lucile vignaud
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
  • Hugo Charles-messance
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
    Department of Clinical medicine, School of Medicine, school of biochemistry and immunology, Trinity Biomedical sciences institute, Trinity College, Dublin, Ireland
  • Wassila Carpentier
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
  • David Rivera
    Department of Cornea and Refractive Surgery, Institute of Ophthalmology, Conde de Valenciana Foundation, Mexico City, Mexico
    Centro de Atencion Integral del Paciente con Diabetes, Instituto Nacional de Ciencias Medicas y Nutricion ‘Salvador Zubiran’, Mexico City, Mexico
  • Aida Jimenez-Corona
    Department of ocular Epidemiology, Institute of Ophthalmology, Conde de Valenciana Foundation, Mexico City, Mexico
  • Sebastien Augustin
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
  • Aude Couturier
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
    Department of Ophthalmology, Hopital Lariboisiere, Universite Paris 7 - Sorbonne-Paris-Cite, Paris, France
  • Jose Alain Sahel
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Enrique O Graue-Hernandez
    Cornea & Refractive Unit, Institute of Ophtalmology, Conde de Valenciana Foundation, Mexico City, Mexico
    Cornea , Refractive Surgery and External Disease, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico
  • Yonathan Garfias
    Research Unit, Cell and Tissue Biology, Institute of Ophthalmology, Conde de Valenciana Foundation, Mexico City, Mexico
    Department of Biochimistry, Universidad Nacional Autonoma, Mexico City, Mexico
  • Florian Sennlaub
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
  • Xavier Guillonneau
    Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
  • Footnotes
    Commercial Relationships   Guillaume Blot, None; lucile vignaud, None; Hugo Charles-messance, None; Wassila Carpentier, None; David Rivera, None; Aida Jimenez-Corona, None; Sebastien Augustin, None; Aude Couturier, None; Jose Sahel, None; Enrique Graue-Hernandez, None; Yonathan Garfias, None; Florian Sennlaub, None; Xavier Guillonneau, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 978. doi:https://doi.org/
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      Guillaume Blot, lucile vignaud, Hugo Charles-messance, Wassila Carpentier, David Rivera, Aida Jimenez-Corona, Sebastien Augustin, Aude Couturier, Jose Alain Sahel, Enrique O Graue-Hernandez, Yonathan Garfias, Florian Sennlaub, Xavier Guillonneau; Dyslipidemia-associated activation of monocyte-derived macrophages in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):978. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Diabetic retinopathy (DR) is a common cause of irreversible blindness. Besides hyperglycemia, dyslipidemia is an often-disregarded risk factor of DR. DR is associated with monocyte (Mo) infiltration and ocular inflammation. We hypothesized that Mos exposure to systemic diabetic environment may promote their differentiation into infiltrating pro-inflammatory macrophages (MPs). We thus analyzed the differentiation of Mos from a cohort of DR patients and compared it to the differentiation of naive Mos exposed to high glucose and/or high lipid concentration.

Methods : We isolated circulating Mos from (i) controls (n=15), (ii) T2DM patients with no sign of DR (n=26) (iii) patients with non-proliferative DR (NPDR) (n=22), and (iv) patients with proliferative DR (PDR) (n=9) and allowed them to differentiate in vitro into MPs for 18 h. High CRP level, renal dysfunction or anti-inflammatory medication donors were excluded from the study. Naive Mos were differentiated in different glucose concentrations (low glucose (LG): 2.5 mM; nomo glucose (NG): 5 mM; or high glucose (HG) 25 mM), or in a combination of glucose/palmitic acid (PA) (LG, NG or HG; PA 500 µM). The cytokine expression was quantified by RT-qPCR. Secretome of PA-treated (or control BSA-treated) MPs was tested for angiogenic activity in rat aortic rings model.

Results : IL-6 and IL-8 expression is elevated in MPs from the 3 diabetic groups compared to control donors. MPs from DR groups (NPDR and PDR) exhibited an elevated level of VEGF and CCL2 expression compared to T2DM. Naive MPs differentiated in LG, NG or HG conditions shown no difference in cytokine expression. Control MPs differentiated under PA exposure demonstrated an elevated expression of all pro-inflammatory cytokines tested, but no for VEGF expression. HG/PA cotreatment increased even more the expression of IL-6 and CCL2. PA-treated MPs secretome had a potent anti-angiogenic effect on rat aortic rings model showing a decrease of 90% (+/- 2 SEM, p<0,01) of sprout numbers.

Conclusions : MPs differentiated from DR patients exhibited a specific inflammatory pattern when compared to control or diabetic patients. PA, but not HG, treatment of naive Mos can partly replicate this specific differentiation. Secretome from PA-treated MPs has a potent anti-angiogenic effect. Our data suggest that Mos/MPs polarized by dyslipidemia are key players in the initial retinal vessel loss.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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