title: Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis.
abstract: Newly formed microcapillary networks arising in adult organisms by angiogenic and inflammatory stimuli contribute to pathologies such as corneal and retinal blindness, tumor growth, and metastasis. Therapeutic inhibition of pathologic angiogenesis has focused on targeting the VEGF pathway, while comparatively little attention has been given to remodeling of the new microcapillaries into a stabilized, functional, and persistent vascular network. Here, we used a novel reversible model of inflammatory angiogenesis in the rat cornea to investigate endogenous factors rapidly invoked to remodel, normalize and regress microcapillaries as part of the natural response to regain corneal avascularity. Rapid reversal of an inflammatory angiogenic stimulus suppressed granulocytic activity, enhanced recruitment of remodelling macrophages, induced capillary intussusception, and enriched pathways and processes involving immune cells, chemokines, morphogenesis, axonal guidance, and cell motility, adhesion, and cytoskeletal functions. Whole transcriptome gene expression analysis revealed suppression of numerous inflammatory and angiogenic factors and enhancement of endogenous inhibitors. Many of the identified genes function independently of VEGF and represent potentially new targets for molecular control of the critical process of microvascular remodeling and regression in the cornea.
authors: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58183 Linköping, Sweden.
authors: Anthony
authors: A
authors: Mukwaya
authors: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58183 Linköping, Sweden.
authors: Beatrice
authors: B
authors: Peebo
authors: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58183 Linköping, Sweden.
authors: Maria
authors: M
authors: Xeroudaki
authors: Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Linköping University, 581 83 Linköping, Sweden.
authors: Zaheer
authors: Z
authors: Ali
authors: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58183 Linköping, Sweden.
authors: Anton
authors: A
authors: Lennikov
authors: Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Linköping University, 581 83 Linköping, Sweden.
authors: Lasse
authors: L
authors: Jensen
authors: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 58183 Linköping, Sweden.
authors: Neil
authors: N
authors: Lagali
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D066253:Vascular Remodeling
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat