Localisation of vascular endothelial growth factor and its receptors to cells of vascular and avascular epiretinal membranes.
OBJECTIVE
Epiretinal membranes (ERMs) arise from a variety of causes or, in some cases, for unknown reasons. Once established, ERMs tend to progress, becoming more extensive and exerting increasing traction along the inner surface of the retina. One possible cause for their progression is the production of growth factors by cells within ERMs that may provide autocrine or paracrine stimulation. Platelet derived growth factor (PDGF) and its receptors have been localised to cells of ERMs and may play such a role. In this study, comparative data were sought for several other growth factors that have been implicated in ERM formation.


METHODS
Immunohistochemical staining of ERMs was done for PDGF-A, PDGF-B, basic fibroblast growth factor (bFGF), three isoforms of transforming growth factor beta (TGF-beta), and vascular endothelial growth factor (VEGF) and its receptors, flt-1 and flk-1/KDR. Expression of flt-1 and flk-1/KDR was examined in cultured retinal pigmented epithelial (RPE) cells and retinal glia from postmortem eyes by immunohistochemistry and by reverse transcription coupled to polymerase chain reaction (RT-PCR).


RESULTS
Staining was most intense and most frequently observed for VEGF and PDGF-A, both in vascular and avascular ERMs. The majority of cells stained for VEGF in nine of 11 (81.8%) diabetic ERMs and in 14 of 24 (58.3%) proliferative vitreoretinopathy ERMs. The receptors for VEGF, flt-1, and flk-1/KDR were also identified on cells in ERMs and on cultured RPE cells. By RT-PCR, mRNA for flt-1 was identified in RPE cells and retinal glia, and mRNA for flk-1/KDR was identified in RPE cells.


CONCLUSIONS
These data show that VEGF and its receptors are localised to both vascular and avascular ERMs and suggest that VEGF, like PDGF-A, may be an autocrine and paracrine stimulator that may contribute to progression of vascular and avascular ERMs.
Chen
Y S
YS
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277, USA.
Hackett
S F
SF
Schoenfeld
C L
CL
Vinores
M A
MA
Vinores
S A
SA
Campochiaro
P A
PA
D016228:Endothelial Growth Factors / Q000032:analysis*; D004730:Endothelium, Vascular; D019773:Epiretinal Membrane / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D017978:Receptors, Growth Factor / Q000032:analysis*
D016228:Endothelial Growth Factors; D017978:Receptors, Growth Factor