Helder André1, Selcuk Tunik2, Monica Aronsson1, Anders Kvanta1. 1. Department of Clinical Neurosciences Section of Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institute, Stockholm, Sweden. 2. Department of Clinical Neurosciences Section of Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institute, Stockholm, Sweden 2Department of Histology and Embryology, School of Medicine, Dicle University, Diyarbakir, Turkey.
Abstract
PURPOSE: To investigate the expression and distribution of neoangiogenic molecules and the role of hypoxia during the development of experimental choroidal neovascularization (CNV). METHODS: Lesions were induced on C57Bl6 mice using laser photocoagulation. Animals were euthanized in a timely manner and eyecups were dissected from enucleated eyes. Choroids were immunostained for pericytes, sprouting endothelial cells (EC), or vascular EC. Choroidal neovascularization lesions where analyzed for tissue hypoxia, hypoxia-inducible factors (HIF), and heat-shock proteins (HSP). RESULTS: Choroidal neovascularization lesions showed a trend of increased cellular recruitment throughout the time-course and the lesions displayed positive staining for angiogenic markers. Both pericytes and sprouting EC displayed a radial progression, while vascular EC displayed a more uniform distribution across the CNV lesions. Furthermore, positive tissue hypoxia staining was observed and associated with expression of HIF-1α and vascular endothelial growth factor (VEGF). CONCLUSIONS: Our data delimitate specific temporal windows during CNV initiation, propagation, maturation, and even recovery in experimental CNV. We show that murine CNV undergoes hypoxia-associated sprouting angiogenesis, and demonstrate involvement of pericytes. Moreover, we have shown expression of HIF-1α to the retinal pigment epithelium surrounding the CNV lesions, together with VEGF upregulation, independently of the HSP response induced by the laser thermal insult.
PURPOSE: To investigate the expression and distribution of neoangiogenic molecules and the role of hypoxia during the development of experimental choroidal neovascularization (CNV). METHODS: Lesions were induced on C57Bl6 mice using laser photocoagulation. Animals were euthanized in a timely manner and eyecups were dissected from enucleated eyes. Choroids were immunostained for pericytes, sprouting endothelial cells (EC), or vascular EC. Choroidal neovascularization lesions where analyzed for tissue hypoxia, hypoxia-inducible factors (HIF), and heat-shock proteins (HSP). RESULTS: Choroidal neovascularization lesions showed a trend of increased cellular recruitment throughout the time-course and the lesions displayed positive staining for angiogenic markers. Both pericytes and sprouting EC displayed a radial progression, while vascular EC displayed a more uniform distribution across the CNV lesions. Furthermore, positive tissue hypoxia staining was observed and associated with expression of HIF-1α and vascular endothelial growth factor (VEGF). CONCLUSIONS: Our data delimitate specific temporal windows during CNV initiation, propagation, maturation, and even recovery in experimental CNV. We show that murine CNV undergoes hypoxia-associated sprouting angiogenesis, and demonstrate involvement of pericytes. Moreover, we have shown expression of HIF-1α to the retinal pigment epithelium surrounding the CNV lesions, together with VEGF upregulation, independently of the HSP response induced by the laser thermal insult.
Authors: Manas R Biswal; Howard M Prentice; George W Smith; Ping Zhu; Yao Tong; C Kathleen Dorey; Alfred S Lewin; Janet C Blanks Journal: J Mol Med (Berl) Date: 2018-08-13 Impact factor: 4.599
Authors: Jin Young Yang; Sanjar Batirovich Madrakhimov; Dong Hyuck Ahn; Hun Soo Chang; Sang Joon Jung; Seung Kwan Nah; Ha Yan Park; Tae Kwann Park Journal: Cell Commun Signal Date: 2019-06-14 Impact factor: 5.712
Authors: Kevin J McHugh; Dian Li; Jay C Wang; Leon Kwark; Jessica Loo; Venkata Macha; Sina Farsiu; Leo A Kim; Magali Saint-Geniez Journal: PLoS One Date: 2019-06-11 Impact factor: 3.240