June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Aflibercept influences the immunocompetence of Dendritic Cells.
Author Affiliations & Notes
  • Jasmin J Weindler
    Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Felix Bock
    Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Matthias Hamdorf
    Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Claus Cursiefen
    Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Footnotes
    Commercial Relationships   Jasmin J Weindler, Deutsche Forschungsgesellschaft (DFG) (F); Felix Bock, Deutsche Forschungsgesellschaft (DFG) (F); Matthias Hamdorf, Deutsche Forschungesellschaft (DFG) (F); Claus Cursiefen, Deutsche Forschungsgesellschaft (DFG) (F)
  • Footnotes
    Support  Deutsche Opthalmologische Gesellschaft (DOG)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 900. doi:
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      Jasmin J Weindler, Felix Bock, Matthias Hamdorf, Claus Cursiefen; Aflibercept influences the immunocompetence of Dendritic Cells.. Invest. Ophthalmol. Vis. Sci. 2021;62(8):900.

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

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Purpose : In the course of keratoplasty, inflammatory processes may lead to a higher risk of graft rejection by changing the immunocompetence of dendritic cells (DCs). Therefore, in this experimental in-vitro study the effect of Aflibercept on the differentiation of DCs was investigated.
We hypothesize that administration of Aflibercept during maturation of DCs can influence the immunocompetence of mature DCs by neutralizing autocrine/paracrine VEGF-A.

Methods : Peripheral Blood Mononuclear Cells of human blood donors (N= 5-6) were differentiated in DC-Medium containing IL-4 and GM-CSF. At the beginning of maturation of immature DCs into mature DCs either 40µg/ml Aflibercept or 40µg/ml Fc-IgG-control was given to the cells. Maturation of DCs was performed with cytokines (CS; containing IL-1b, IL-6, TNFa and PGE) or Lipopolysaccharide (LPS).
After entering the stadium of mature DCs flow cytometry was performed with the focus on DC-specific surface markers (CD11c, CD40, MHC II), co-stimulatory receptors for T-cell stimulation (CD80, CD83, CD86) and the VEGF receptors VEGFR1 and VEGFR2.
Also, RNA was harvested of treated mature DCs and mRNA-levels of VEGF-A and VEGFR1 were investigated by using Realtime-PCR (RT-PCR).
Statistical analysis was performed with GraphPad Prism using a t-test or Man-Whitney-U-test.

Results : Aflibercept administrated during maturation of dendritic cells induced significant upregulation of the receptor CD11c (CS: p: 0.0145; 111.7%±44.1) and a significant downregulation of the co-stimulatory receptors CD83 (LPS: p: 0.032; 97.4%±16.8) and CD86 (LPS: p: 0.047; 94.01%±6.7) as well as VEGFR1 (CS: p: 0.0095; 47.1%±19.1).
Furthermore, the frequency of VEGFR1-positive cells decreased significantly under Aflibercept treatment (CS: p: <0.0001; 21.4%±14.7; LPS: p: 0.0001; 36.1%±8.5).
No differences of the VEGF-A-mRNA-level or the VEGFR1-mRNA level was seen in the RT-PCR.

Conclusions : Aflibercept has a direct effect on dendritic cell maturation. Aflibercept modulates DC immunocompetence by downregulation of the receptors CD83 and CD86. The downregulation of the receptor VEGFR1 as well as the reduced expression of VEGFR1 on DCs treated with Aflibercept suggest that Aflibercept interacts with this receptor or could have an effect on the binding of VEGF-A on this receptor.

This is a 2021 ARVO Annual Meeting abstract.


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