A Case of Abnormal Lymphatic-Like Differentiation and Endothelial Progenitor Cell Activation in Neovascularization Associated with Hemi-Retinal Vein Occlusion.
OBJECTIVE
Pathological vascular differentiation in retinal vein occlusion (RVO)-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or endothelial progenitor cell activity has not been studied in this disease.


METHODS
Vitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC) adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin (PDPN), and prospero-related homeobox protein 1 (Prox-1). Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67) and expression of the stem cell marker CD117.


RESULTS
The specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity.


CONCLUSIONS
Intraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO.
Unit of Vitreoretinal Surgery, Department of Ophthalmology, Helsinki, Finland.
Sirpa
S
Loukovaara
Genome-Scale Biology Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Erika
E
Gucciardo
Genome-Scale Biology Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Pauliina
P
Repo
Department of Pathology, Haartman Institute, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Jouko
J
Lohi
Department of Pathology, Haartman Institute, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Petri
P
Salven
Genome-Scale Biology Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Kaisa
K
Lehti
Endothelial progenitor cell; Hemi-retinal vein occlusion; Immunohistochemistry; Lymphatic endothelial cell; Lymphatic vessel endothelial hyaluronan receptor 1; Platelet endothelial cell adhesion molecule 1; Podoplanin; Proliferative diabetic retinopathy; Prospero-related homeobox gene 1; Vascular endothelial stem cell