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Indications of lymphatic endothelial differentiation and endothelial progenitor cell activation in the pathology of proliferative diabetic retinopathy
Author(s) -
Loukovaara Sirpa,
Gucciardo Erika,
Repo Pauliina,
Vihinen Helena,
Lohi Jouko,
Jokitalo Eija,
Salven Petri,
Lehti Kaisa
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.12741
Subject(s) - progenitor cell , pathology , endothelial stem cell , lymphatic system , lymphatic endothelium , biology , stem cell marker , endothelial progenitor cell , stem cell , medicine , microbiology and biotechnology , in vitro , biochemistry
Abstract Purpose Proliferative diabetic retinopathy ( PDR ) is characterized by ischaemia‐ and inflammation‐induced neovascularization, but the pathological vascular differentiation in PDR remains poorly characterized. Here, endothelial progenitor and growth properties, as well as potential lymphatic differentiation, were investigated in the neovascular membrane specimens from vitrectomized patients with PDR . Methods The expression of pan‐endothelial CD 31 ( PECAM ‐1), ETS ‐related gene ( ERG ), α ‐smooth muscle actin ( α ‐ SMA ), and stem/progenitor cell marker CD 117 (c‐kit) and cell proliferation marker Ki67 was investigated along with the markers of lymphatic endothelial differentiation (vascular endothelial growth factor receptor ( VEGFR )‐3; prospero‐related homeobox gene‐1 (Prox‐1), lymphatic vessel endothelial receptor [ LYVE )‐1 and podoplanin ( PDPN )] by immunohistochemistry. Lymphocyte antigen CD 45 and pan‐macrophage marker CD 68 were likewise investigated. Results All specimens displayed CD 31, ERG and α ‐ SMA immunoreactivity in irregular blood vessels. Unexpectedly, VEGFR 3 and Prox‐1 lymphatic marker positive vessels were also detected in several tissues. Prox‐1 was co‐expressed with CD 117 in lumen‐lining endothelial cells and adjacent cells, representing putative endothelial stem/progenitor cells and pro‐angiogenic perivascular cells. Immunoreactivity of CD 45 and CD 68 was detectable in all investigated diabetic neovessel specimens. PDPN immunoreactivity was also detected in irregular lumen‐forming structures, but these cells lacked CD 31 and ERG that mark blood and lymphatic endothelium. Conclusions Although the inner part of human eye is physiologically devoid of lymphatic vessels, lymphatic differentiation associated with endothelial stem/progenitor cell activation may be involved in the pathogenesis of human PDR . Further studies are warranted to elucidate whether targeting lymphatic factors could be beneficial in the treatment of patients with the sight‐threatening forms of DR .