Apelin is a crucial factor for hypoxia-induced retinal angiogenesis.
OBJECTIVE
To investigate the role of endogenous apelin in pathological retinal angiogenesis.


RESULTS
The progression of ischemic retinal diseases, such as diabetic retinopathy, is closely associated with pathological retinal angiogenesis, mainly induced by vascular endothelial growth factor (VEGF) and erythropoietin. Although antiangiogenic therapies using anti-VEGF drugs are effective in treating retinal neovascularization, they show a transient efficacy and cause general adverse effects. New therapeutic target molecules are needed to resolve these issues. It was recently demonstrated that the apelin/APJ system, a newly deorphanized G protein-coupled receptor system, is involved in physiological retinal vascularization. Retinal angiography and mRNA expression were examined during hypoxia-induced retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Compared with age-matched control mice, retinal apelin expression was dramatically increased during the hypoxic phase in oxygen-induced retinopathy model mice. APJ was colocalized in proliferative cells, which were probably endothelial cells of the ectopic vessels in the vitreous body. Apelin deficiency hardly induced hypoxia-induced retinal angiogenesis despite the upregulation of VEGF and erythropoietin mRNA in oxygen-induced retinopathy model mice. Apelin small and interfering RNA suppressed the proliferation of endothelial cells independent of the VEGF/VEGF receptor 2 signaling pathway.


CONCLUSIONS
These results suggest that apelin is a prerequisite factor for hypoxia-induced retinal angiogenesis.
Kasai
Atsushi
A
Department of Pharmacotherapeutics, Setsunan University, Hirakata, Osaka 565-0871, Japan. kasai@pharm.setsunan.ac.jp
Ishimaru
Yuki
Y
Kinjo
Toshihiko
T
Satooka
Tatsuya
T
Matsumoto
Nao
N
Yoshioka
Yasuhiro
Y
Yamamuro
Akiko
A
Gomi
Fumi
F
Shintani
Norihito
N
Baba
Akemichi
A
Maeda
Sadaaki
S
D054392:Adipokines; D000818:Animals; D000073861:Apelin; D002352:Carrier Proteins / Q000009:adverse effects / Q000502:physiology*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D015861:Retinal Neovascularization / Q000209:etiology / Q000503:physiopathology*
D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins