Maturation of the fetal human choriocapillaris
Takayuki Baba 1,
Rhonda Grebe 1,
Takuya Hasegawa 1,
Imran Bhutto 1,
Carol Merges 1,
D Scott McLeod 1,
and
Gerard A. Lutty 2*
1 Johns Hopkins Hospital, Wilmer Ophthalmological Institute, Baltimore, Maryland, United States
2 Johns Hopkins Hospital, Wilmer Ophthalmological Institute, 600 North Wolfe Street, Baltimore, Maryland, 21287-9115, United States
* To whom correspondence should be addressed. E-mail: glutty{at}jhmi.edu.
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Abstract |
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Purpose. The purpose of this study was to examine the structural and functional maturation of the choriocapillaris (CC). We sought to determine when fenestrations formed, pericytes invest the capillaries and endothelial cells became functional.
Methods. Immunohistochemistry was performed on cryopreserved sections of embryonic/fetal human eyes from 7 to 22 weeks gestation (WG) using antibodies against PAL-E, PV-1 (fenestrations), carbonic anhydrase IV (CA IV), eNOS, and alpha smooth muscle actin (alpha SMA) and NG2 (two pericyte markers) and endothelial cell (EC) marker (CD31). Alkaline phosphatase (APase) enzymatic activity was demonstrated by enzyme histochemistry. Transmission electron microscopy (TEM) was performed on 11, 14, 16 and 22 WG eyes. Adult human eyes were used as positive controls.
Results. All EC markers were present in CC by 7 WG. PAL-E, CA IV and eNOS immunoreactivities and APase activity were present in CC by 7-9 WG. TEM analysis demonstrated how structurally immature this vasculature was even at 11 WG: no basement membrane, absence of pericytes, and poorly formed lumens that were filled with filopodia. The few fenestrations that were observed were often present within the luminal space in the filopodia. Contiguous fenestrations and significant PV-1 were not observed until 21-22 WG. Alpha SMA was prominent at 22 WG and the maturation of pericytes was confirmed by TEM.
Conclusions. It appears that EC and their precursors express enzymes present in adult CC well before they are structurally mature. Although EC make tight junctions early in development, contiguous fenestrations and mature pericytes occur much later in development.
Key Words:
choriocapillaris, fenestrations, fetal, immunohistochemistry, pericytes, ultrastructure
