Novel discovery of LYVE-1 expression in the hyaloid vascular system.
OBJECTIVE
The hyaloid vascular system (HVS) is a transient network nourishing developing eyes and has been widely used as a natural model to study blood vessel regression. Failure of its regression in humans leads to several blinding diseases. Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a recently defined lymphatic marker that is also expressed by a subpopulation of macrophages. To date, there is no report on its expression in the HVS. This study was conducted to investigate whether LYVE-1 is expressed in the HVS and how it is associated with the vascular structure and macrophage phenotype.


METHODS
Normal C57BL/6 mouse eyeballs were sampled from embryonic day (E) 10.5 to postnatal (P) and adult stages for immunofluorescent microscopic studies with antibodies against LYVE-1, CD31 (panendothelial cell marker), and F4/80 (macrophage marker). Additionally, Angiopoietin-2 (Ang-2) knockout mice with abnormally persistent HVS were examined.


RESULTS
The LYVE-1 expression was detected on normal HVS between E12.5 and P14. The LYVE-1(+) cells were F4/80(+) but CD31(-), indicating a macrophage lineage. Additionally, LYVE-1(+) cells bud on CD31(+) vessels and constitute an integral part of the network in both normal developing and Ang-2 knockout mice.


CONCLUSIONS
This study provides the first evidence that the HVS contains a LYVE-1(+) cellular component in both physiological and pathologic conditions. This novel finding not only provides a new concept in defining the embryogenesis and pathogenesis of the HVS, it also leads to a completely natural model in which to study the functions of the LYVE-1 pathway, an important topic for lymphatic research as well.
Zhang
Hui
H
Center for Eye Disease and Development, School of Optometry, University of California, Berkeley, CA 94720, USA.
Tse
Julie
J
Hu
Xuemei
X
Witte
Marlys
M
Bernas
Michael
M
Kang
Jinjoo
J
Tilahun
Firehiwott
F
Hong
Young-Kwon
YK
Qiu
Mengsheng
M
Chen
Lu
L
D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000378:metabolism*; D007908:Lens, Crystalline / Q000098:blood supply / Q000196:embryology*; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009880:Ophthalmic Artery / Q000196:embryology* / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014822:Vitreous Body / Q000098:blood supply / Q000196:embryology*
D042702:Angiopoietin-2; D000943:Antigens, Differentiation; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C492273:LYVE1 protein, mouse; C036763:monocyte-macrophage differentiation antigen