Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor Are Dispensable for Ocular Neovascularization—Brief Report. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Liyanage, Sidath E.; Fantin, Alessandro; Villacampa, Pilar; Lange, Clemens A.; Denti, Laura; Cristante, Enrico; Smith, Alexander J.; Ali, Robin R.; Luhmann, Ulrich F.; Bainbridge, James W.; Ruhrberg, Christiana
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 36:Issue 1(2016)
• Publication Date: 2016-01
• Subjects: choroidal neovascularization -- diabetic retinopathy -- macular degeneration -- myeloid cells -- vascular endothelial growth factor A; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.306681
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1α (HIF1α) and hypoxia-inducible factor-2α (HIF2α) as myeloid-derived regulators of ONV remains to be determined. Approach and Results—: We used 2 mouse models of ONV, choroidal neovascularization and oxygen-induced retinopathy, to show that Vegfa is highly expressed by several cell types, but not myeloid cells during ONV. Moreover, myeloid-specific VEGF ablation did not reduce total ocular VEGF during choroidal neovascularization or oxygen-induced retinopathy. In agreement, the conditional inactivation of Vegfa, Hif1a, or Epas1 in recruited and resident myeloid cells that accumulated at sites of neovascularization did not significantly reduce choroidal neovascularization or oxygen-induced retinopathy. Conclusions—: The finding that myeloid cells are not a significant local source of VEGF in these rodent models of ONV suggests that myeloid function in neovascular eye disease differs from skin wound healing and other neovascular pathologies. Abstract : Supplemental Digital Content is available in the text.