Retardation of retinal vascular development in apelin-deficient mice.
OBJECTIVE
Apelin is an endogenous ligand for the G protein-coupled receptor, APJ, and participates in multiple physiological processes. To identify the roles of endogenous apelin, we investigated the phenotype of apelin-deficient (apelin-KO) mice.


RESULTS
Apelin-KO mice showed impaired retinal vascularization and ocular development, which were analyzed by histology, immunohistochemistry, real-time polymerase chain reaction, and the mouse corneal micropocket assay. Apelin-KO mice showed significantly impaired retinal vascularization in the early postnatal period. Retinal apelin/APJ mRNAs were transiently upregulated during the first 2 postnatal weeks but were undetectable in adults. There were no differences in VEGF or FGF2 mRNA expression, or in the morphology and localization of GFAP-positive astrocytes, in the apelin-KO retinas at P5. The corneal pocket assay showed that angiogenic responses to VEGF and FGF2 were remarkably decreased in apelin-KO mice. The reduced responses to VEGF and FGF2 in apelin-KO mice were partially restored by apelin, but apelin alone did not induce angiogenesis.


CONCLUSIONS
Our results suggest that spatiotemporally regulated apelin/APJ signaling participates in retinal vascularization in a cooperative manner with VEGF or FGF2, and contributes to normal ocular development.
Kasai
Atsushi
A
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, OsakaUniversity, Japan.
Shintani
Norihito
N
Kato
Hideaki
H
Matsuda
Satoshi
S
Gomi
Fumi
F
Haba
Ryota
R
Hashimoto
Hitoshi
H
Kakuda
Michiya
M
Tano
Yasuo
Y
Baba
Akemichi
A
D054392:Adipokines; D000818:Animals; D000831:Animals, Newborn; D000073861:Apelin; D000075244:Apelin Receptors; D002196:Capillaries / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000098:blood supply*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; D042787:Receptor, TIE-2