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


RESULTS
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).


CONCLUSIONS
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.
Carrington
L
L
Department of Optometry and Vision Sciences, University of Cardiff, United Kingdom.
McLeod
D
D
Boulton
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016753:Interleukin-10 / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000276:immunology* / Q000494:pharmacology; D012160:Retina / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10