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Chikako Hara, Atsushi Kasai, Fumi Gomi, Tatsuya Satooka, Susumu Sakimoto, Kei Nakai, Yasuhiro Yoshioka, Akiko Yamamuro, Sadaaki Maeda, Kohji Nishida; Laser-Induced Choroidal Neovascularization in Mice Attenuated by Deficiency in the Apelin-APJ System. Invest. Ophthalmol. Vis. Sci. 2013;54(6):4321-4329. doi: 10.1167/iovs.13-11611.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of the apelin-APJ system in the development of choroidal neovascularization (CNV).
Experimental CNV was induced by laser photocoagulation in wild-type (WT), apelin-deficient (apelin-KO), and apelin receptor (APJ)–deficient (APJ-KO) mice. The gene expression levels of angiogenic or inflammatory factors were determined by quantitative real-time reverse transcription–polymerase chain reaction. APJ expression in CNV lesions was examined by immunohistochemistry. The sizes of the CNV lesions in the three mouse models were measured and compared histologically using isolectin B4 staining. Macrophage recruitment was measured by flow cytometric analysis. Proliferation of endothelial cells was determined using the alamar Blue assay.
Laser photocoagulation significantly increased expression of apelin and APJ in the retina–retinal pigment epithelium (RPE) complex. APJ immunoreactive cells were found in the CNV lesions and colocalized with platelet endothelial cell adhesion molecule-1, an endothelial cell marker. The sizes of the CNV lesions in apelin-KO or APJ-KO mice decreased significantly compared with those in the WT mice. Macrophages in the RPE complex of the apelin-KO mice, in which gene expression of the inflammatory factors was almost equal to that in WT mice, were recruited as a result of laser photocoagulation to the same degree as in WT mice. In addition, apelin small and interfering RNA (siRNA) suppressed proliferation of endothelial cells independently of vascular endothelial growth factor (VEGF) receptor 2 signaling, while VEGF increased expression of apelin and APJ in human umbilical vein endothelial cells.
The results suggested that the apelin-APJ system contributes to CNV development partially independent of the VEGF pathway.
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