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Updated: May 11, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Laser-induced choroidal neovascularization in mice attenuated by deficiency in the apelin-APJ system
Chikako Hara1, Atsushi Kasai, Fumi Gomi
1Department of Ophthalmology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Purpose:
To investigate the role of the apelin-APJ system in the development of choroidal neovascularization (CNV).
Methods:
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.
Results:
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.
Conclusions:
The results suggested that the apelin-APJ system contributes to CNV development partially independent of the VEGF pathway.
Insights
The apelin-APJ system plays a role in choroidal neovascularization (CNV) development. Inhibiting apelin or its receptor (APJ) reduced CNV lesion size in mice, suggesting a therapeutic target.
Area of Science:
- Ophthalmology
- Molecular Biology
- Vascular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- The molecular mechanisms underlying CNV development are not fully understood.
- The apelin-APJ system's role in CNV remains to be elucidated.
Purpose of the Study:
- To investigate the involvement of the apelin-APJ signaling pathway in the pathogenesis of choroidal neovascularization (CNV).
Main Methods:
- Experimental CNV was induced in wild-type, apelin-deficient, and APJ-deficient mice.
- Gene expression of angiogenic and inflammatory factors was quantified.
- CNV lesion size, macrophage recruitment, and endothelial cell proliferation were assessed.
Main Results:
- Apelin and APJ expression increased in laser-induced CNV.
- Mice lacking apelin or APJ exhibited significantly smaller CNV lesions.
- Apelin inhibition reduced endothelial cell proliferation, partly independent of VEGF signaling.
Conclusions:
- The apelin-APJ system is a significant contributor to CNV development.
- Targeting the apelin-APJ pathway may offer a novel therapeutic strategy for CNV.
- This system's contribution to CNV is partially independent of the VEGF pathway.
