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Louise Carrington, David McLeod, Mike Boulton; IL-10 and Antibodies to TGF-β2 and PDGF Inhibit RPE-Mediated Retinal Contraction. Invest. Ophthalmol. Vis. Sci. 2000;41(5):1210-1216.
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purpose. Retinal pigment epithelial (RPE) cells are believed to play a pivotal
role in the formation and contraction of epiretinal membranes in
proliferative vitreoretinopathy (PVR). In the present study, an organ
culture method was used that mimics the contractile stage of PVR, to
investigate the contribution of a variety of growth factors in human
RPE cell–mediated contraction of the retina.
methods. Cultured human RPE cells were seeded onto bovine retinal explants.
After attachment, cultures received one of the following exogenous
growth factors: platelet-derived growth factor (PDGF)-AB, PDGF-BB,
basic fibroblast growth factor (bFGF), transforming growth factor
(TGF)-β1, TGF-β2, or interleukin (IL)-10;
or a neutralizing antibody to PDGF and/or TGF-β2. Control
explants were either untreated or received a null antibody. Contraction
was assessed by image analysis and expressed as percentage reduction in
results. RPE cells produced a more than 50% contraction of the retina after 7
days in untreated samples. PDGF and TGF-β2 stimulated
RPE-mediated contraction by a further 20% at 100 ng/ml. IL-10
decreased contraction by 63%, whereas the other growth factors gave
rise to similar contraction to untreated controls. Neutralizing
antibodies against PDGF and TGF-β2 reduced RPE-mediated
contraction by up to 70% in comparison with untreated controls. The
neutralizing antibodies also inhibited the effects of exogenous PDGF
and TGF-β2 on RPE-mediated contraction of the retina
(P < 0.01).
conclusions. These findings confirm a role for both PDGF and TGF-β2 in
RPE cell–mediated contraction of the retina. Such contraction can be
inhibited by neutralizing antibodies against PDGF and
TGF-β2, which, together with IL-10, are putative
candidates for therapeutic intervention in
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