June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalization in the course of proliferative retinopathy
Author Affiliations & Notes
  • Matina Economopoulou
    Ophthalmology, University Clinic Dresden, Dresden, Germany
  • Nemanja Avramovic
    Dept of Pathobiochemistry, Dresden, Germany
  • Anne Klotzsche von Ameln
    Dept of Pathobiochemistry, Dresden, Germany
  • Lutz E Pillunat
    Ophthalmology, University Clinic Dresden, Dresden, Germany
  • Triantafyllos Chavakis
    Dept of Pathobiochemistry, Dresden, Germany
  • Footnotes
    Commercial Relationships Matina Economopoulou, None; Nemanja Avramovic, None; Anne Klotzsche von Ameln, None; Lutz Pillunat, None; Triantafyllos Chavakis, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2048. doi:
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      Matina Economopoulou, Nemanja Avramovic, Anne Klotzsche von Ameln, Lutz E Pillunat, Triantafyllos Chavakis; Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalization in the course of proliferative retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2048.

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

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Abstract

Purpose: In proliferative retinopathies, such as proliferative diabetic retinopathy and retinopathy of prematurity (ROP), the hypoxia response in the retina is sustained by the failure of the retina to revascularize its ischemic areas. Non-resolving retina ischemia/hypoxia results in upregulation of pro-angiogenic factors and pathologic neovascularization with ectopic, fragile neovessels. Promoting revascularization of the retinal avascular area could interfere with this vicious cycle and lead to regression of neovessels as well as vessel normalization. Here, we examined the function of endothelial junctional adhesion molecule-C (JAM-C) in the context of vasoproliferative retinopathies.

Methods: Endothelial specific JAM-C deficient (EC-JAM-C KO) mice and littermate JAM-C proficient (EC-JAM-C WT) mice were subjected to the ROP model. The total retinal vascularisation was asessed by quantification of PECAM-1 immunofluorescent staining in retinal sections of EC-JAM-C KO and WT mice. Furthermore the avascular area and the tip cell formation in the ROP retina was quantified in isolectin B4 stained retinal wholemounts. Finally the sprouting and spreading ability of JAM-C deficient and sufficient human retinal endothelial was tested in vitro.

Results: An increase in total retinal vascularization was found due to endothelial JAM-C deficiency, whereas neovessel formation was not affected. Instead, the re-vascularising network was increased in the absence of endothelial JAM-C, thereby leading to a significant reduction in avascular area in the EC-JAM-C KO mice. Enhanced vessel normalization in EC-JAM-C-KO mice was attributed to a higher number of tip cells present at the interface between vascular and avascular area in these mice as compared to their littermate controls. Consistently, JAM-C inactivation in human retinal microvascular endothelial cells resulted in increased spreading to fibronectin and enhanced sprouting in vitro in a manner dependent on the activation of the small GTPase RAP1.

Conclusions: Taken together, endothelial deletion of JAM-C promoted endothelial cell sprouting, and consequently vessel normalization and revascularization of the hypoxic retina without altering pathologic neovascularization. Thus, targeting endothelial JAM-C may provide a novel therapeutic strategy for promoting vessel normalization in the treatment of proliferative retinopathies.

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