Co-expression of endothelial and neuronal nitric oxide synthases in the developing vasculatures of the human fetal eye

D. Scott McLeod, Takayuki Baba, Imran A. Bhutto, Gerard A. Lutty

Research output: Contribution to journalArticlepeer-review


Background: Nitric oxide (NO) is a multifunctional gaseous molecule that regulates various physiological functions in both neuronal and non-neuronal cells. NO is synthesized by nitric oxide synthases (NOSs), of which three isoforms have been identified. Neuronal NOS (nNOS) and endothelial NOS (eNOS) constitutively produce low levels of NO as a cellsignaling molecule in response to an increase in intracellular calcium concentration. Recent data have revealed a predominant role of eNOS in both angiogenesis and vasculogenesis. Methods: The immunohistochemical localization of nNOS and eNOS was investigated during embryonic and fetal ocular vascular development from 7 to 21 weeks gestation (WG) on sections of cryopreserved tissue. Results: eNOS was confined to endothelial cells of developing vessels at all ages studied. nNOS was prominent in nuclei of vascular endothelial and smooth muscle cells in the fetal vasculature of vitreous and choriocapillaris. nNOS was also prominent in the nuclei of CXCR4 + progenitors in the inner retina and inner neuroblastic layer. Conclusions: These findings demonstrate co-expression of n- and eNOS isoforms in different compartments of vasoformative cells during development. Nuclear nNOS was present in vascular and nonvascular progenitors as well as endothelial cells and pericytes. This suggests that nNOS may play a role in the transcription regulatory systems in endothelial cells and pericytes during ocular hemo-vasculogenesis, vasculogenesis, and angiogenesis.

Original languageEnglish (US)
Pages (from-to)839-848
Number of pages10
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Issue number6
StatePublished - Jun 2012


  • Choroidal vasculature
  • Fetal vasculature of vitreous
  • Nitric oxide synthase
  • Nucleus
  • Progenitors
  • Retinal vasculature

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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