Developmental regression of hyaloid vasculature is triggered by neurons

Yusuke Yoshikawa, Toru Yamada, Ikue Tai-Nagara, Keisuke Okabe, Yuko Kitagawa, Masatsugu Ema, Yoshiaki Kubota

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


Vascular development involves not only vascular growth, but also regression of transient or unnecessary vessels. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which spontaneously degenerates when the retinal blood vessels start to grow. Failure of the hyaloid vessels to regress leads to disease in humans, persistent hyperplastic primary vitreous, which causes severe intraocular hemorrhage and impairs visual function. However, the mechanism underlying the endogenous program that mediates spontaneous regression of the hyaloid vessels is not well understood. In this study, we identify a robust switch triggering this program directed by neurons in mice. Marked up-regulation of vascular endothelial growth factor (VEGF) receptor 2 (VEG FR2) occurs in retinal neurons just after birth via distal-multipotent-mesodermal enhancer, a hemangioblast- specific enhancer of VEG FR2. Genetic deletion of neuronal VEG FR2 interrupts this program, resulting in massive hyaloid vessels that persist even during late postnatal days. This abnormality is caused by excessive VEGF proteins in the vitreous cavity as a result of impairment in the neuronal sequestration of VEGF. Collectively, our data indicate that neurons trigger transition from the fetal to the postnatal circulatory systems in the retina.

Original languageEnglish
Pages (from-to)1175-1183
Number of pages9
JournalJournal of Experimental Medicine
Issue number7
Publication statusPublished - 2016 Jun 27

ASJC Scopus subject areas

  • General Medicine


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