IL-10 and antibodies to TGF-beta2 and PDGF inhibit RPE-mediated retinal contraction

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.

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)-beta1, TGF-beta2, or interleukin (IL)-10; or a neutralizing antibody to PDGF and/or TGF-beta2. Control explants were either untreated or received a null antibody. Contraction was assessed by image analysis and expressed as percentage reduction in retinal area.

RPE cells produced a more than 50% contraction of the retina after 7 days in untreated samples. PDGF and TGF-beta2 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-beta2 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-beta2 on RPE-mediated contraction of the retina (P < 0.01).

These findings confirm a role for both PDGF and TGF-beta2 in RPE cell-mediated contraction of the retina. Such contraction can be inhibited by neutralizing antibodies against PDGF and TGF-beta2, which, together with IL-10, are putative candidates for therapeutic intervention in PVR.