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

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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 cell-signaling molecule in response to an increase in intracellular calcium concentration. Recent data have revealed a predominant role of eNOS in both angiogenesis and vasculogenesis.


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.


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.


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.

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Correspondence to Gerard A. Lutty.

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NIH grants: EY-01765 (Wilmer), RO1-EY09357 (GL), and R01-EY016151 (GL), Research to Prevent Blindness (Wilmer), the Foundation Fighting Blindness (GL), and Altsheler Durell Foundation. Gerard Lutty received an RPB senior scientific investigator award and was an American Heart Association Established Investigator.

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McLeod, D.S., Baba, T., Bhutto, I.A. et al. Co-expression of endothelial and neuronal nitric oxide synthases in the developing vasculatures of the human fetal eye. Graefes Arch Clin Exp Ophthalmol 250, 839–848 (2012).

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