June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Involvement of N-formyl peptide receptors in modulating the pro-angiogenic/pro-inflammatory activity of human vitreous in proliferative diabetic retinopathy (PDR)
Author Affiliations & Notes
  • Mohd Imtiaz Nawaz
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Sara Rezzola
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Michela Corsini
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Paola Chiodelli
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Anna Cancarini
    Department of Ophthalmology, University of Brescia, BRESCIA, Italy
  • Daniela Coltrini
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Stefania Mitola
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Roberto Ronca
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Mirella Belleri
    Department of Chemical Sciences, “Federico II” University of Naples, Naples, Italy
  • Liliana Lista
    Department of Chemical Sciences, “Federico II” University of Naples, Naples, Italy
  • Dario Rusciano
    Sooft Italia Spa, Montegiorgio, Italy
  • Mario De Rosa
    Department of Experimental Medicine, Second University of Naples, Naples, Italy
  • Vincenzo Pavone
    Department of Chemical Sciences, “Federico II” University of Naples, Naples, Italy
  • Francesco Semeraro
    Department of Ophthalmology, University of Brescia, BRESCIA, Italy
  • Marco Presta
    Department of Molecular and Translational Medicine, University of Brescia, BRESCIA, BS, Italy
  • Footnotes
    Commercial Relationships   Mohd Nawaz, None; Sara Rezzola, None; Michela Corsini, None; Paola Chiodelli, None; Anna Cancarini, None; Daniela Coltrini, None; Stefania Mitola, None; Roberto Ronca, None; Mirella Belleri, None; Liliana Lista, None; Dario Rusciano, None; Mario De Rosa, None; Vincenzo Pavone, None; Francesco Semeraro, None; Marco Presta, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5209. doi:
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      Mohd Imtiaz Nawaz, Sara Rezzola, Michela Corsini, Paola Chiodelli, Anna Cancarini, Daniela Coltrini, Stefania Mitola, Roberto Ronca, Mirella Belleri, Liliana Lista, Dario Rusciano, Mario De Rosa, Vincenzo Pavone, Francesco Semeraro, Marco Presta; Involvement of N-formyl peptide receptors in modulating the pro-angiogenic/pro-inflammatory activity of human vitreous in proliferative diabetic retinopathy (PDR). Invest. Ophthalmol. Vis. Sci. 2017;58(8):5209.

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

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Abstract

Purpose : PDR is characterized by neovascularization and a persistent grade of inflammation. N-formyl peptide receptors (FPRs) belong to a transmembrane G protein-coupled receptor superfamily able to modulate angiogenic and inflammatory responses. However, their involvement in PDR remains to be elucidated. Here, we examined FPR expression in human umbilical vein endothelial cells (HUVECs). We further assessed the capacity of vitreous fluid obtained from PDR patients after pars plana vitrectomy to induce pro-angiogenic/pro-inflammatory responses in endothelium and the contribution of FPR inhibitors to abrogate these responses.

Methods : Expression of FPRs (FPR1-FPR3) was examined in HUVECs at mRNA and protein levels. The capacity of PDR vitreous samples to induce pro-angiogenic and pro-inflammatory responses in HUVECs was assessed by cell proliferation, motility and sprouting assays and by evaluating the activation of pro-inflammatory transcription factors, disruption of junctional protein and RT-PCR analysis of upregulation leukocyte adhesion molecules, respectively. In vivo, the pro-angiogenic/pro-inflammatory activity of PDR vitreous was tested in the chick embryo chorioallantoic membrane (CAM) assay. Finally, FPR1 inhibitor cyclosporin (CsH), FPR2 inhibitor WRW4 (Trp-Arg-Trp-Trp-Trp-Trp), pan-FPR inhibitor BOC-Phe-Leu-Phe-Leu-Phe (BOC-FLFLF), and the novel FPR inhibitor Ac-L-Arg-Aib-L Arg-L-Ca(Me)Phe-NH tetrapeptide (UPARANT) were tested for their capacity to inhibit the biological responses elicited by PDR vitreous in vitro and in vivo.

Results : Data from semi-quantitative RT-PCR, FACS and Western blot analyses indicate that primary HUVEC cultures express FPR3 but not FPR1 and FPR2. PDR vitreous activates a pro-angiogenic/pro-inflammatory phenotype in endothelial cells. Accordingly, PDR vitreous triggers a potent angiogenic/inflammatory response in vivo. The pan-FPR inhibitor BOC-FLFLF and the novel FPR antagonist UPARANT inhibited the capacity of PDR vitreous to stimulate the sprouting of HUVEC spheroids embedded in 3D-fibrin gel and neovessel formation in the CAM assay.

Conclusions : Together, our data point to the involvement of FPRs in modulating the pro-angiogenic/pro-inflammatory response of PDR vitreous. FPRs may represent a target for the development of novel anti-inflammatory/anti-angiogenic approaches for PDR therapy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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