Endothelial progenitor cells in pterygium pathogenesis.
OBJECTIVE
The pathogenesis of pterygium is not well known, and controversy exists about the cell origins and the nature of initial trigger required for its development. We investigated whether endothelial progenitor cells (EPCs) are involved in pathogenesis of pterygium and the mechanism underlying the selective recruitment of EPCs during this process.


METHODS
We studied 13 normal controls and 28 pterygium patients (primary (n=15), recurrent (n=13)). Substance-P, vascular endothelial growth factor (VEGF), and stem cell factor (SCF) were measured in plasma and tears using ELISA, and circulating CD34(+) and c-kit(+) mononuclear cells (MNCs) by flow cytometry. Anterior segment fluorescein angiography (FAG) was performed to evaluate hypoxic conditions in the early stage of pterygium. Surgically removed pterygial tissues were analyzed immunohistochemically using the progenitor cell markers, CD34, c-kit, VEGFR-1, and VEGFR-2.


RESULTS
Anterior segment FAG findings showed an increase in non-perfusion areas and attenuated vessels in the nasal limbus during early-stage pterygium. Circulating CD34(+) MNCs and c-kit(+) MNCs were increased in pterygium groups compared with normal controls. Systemic and local cytokines including SP, VEGF, and SCF in pterygium groups were also elevated and showed positive correlations with CD34(+) and c-kit(+) MNC numbers. Immunohistochemical analysis of pterygium showed strong progenitor cell marker immunoreactivities.


CONCLUSIONS
EPCs might be involved in pterygium development, and ocular hypoxia triggers this neovascularization by recruiting EPCs derived from the bone marrow via the production of systemic and local cytokines.
Lee
J K
JK
Department of Ophthalmology, College of Medicine, Chung-Ang University, Seoul, Korea. jck50ey@kornet.net
Song
Y S
YS
Ha
H S
HS
Park
J H
JH
Kim
M K
MK
Park
A J
AJ
Kim
J C
JC
D017677:Age Distribution; D000368:Aged; D002630:Chemotactic Factors / Q000032:analysis; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications; D018836:Inflammation Mediators / Q000032:analysis; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000150:complications / Q000378:metabolism / Q000473:pathology; D011625:Pterygium / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D012008:Recurrence; D017678:Sex Distribution; D019089:Stem Cell Factor / Q000032:analysis; D013234:Stem Cells / Q000473:pathology*; D013373:Substance P / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D002630:Chemotactic Factors; D018836:Inflammation Mediators; D019089:Stem Cell Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013373:Substance P