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Steven Pennock, Marc-Andre Rheaume, Shizuo Mukai, Joanne A. Matsubara, Jing Cui, David Maberley, Patrick Ma, Arif Samad, R.J. van Geest, Andrius Kazlauskas; A Novel Strategy To Develop Therapeutic Approaches To Prevent Proliferative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4924.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) remains an obstacle to successful repair of rhegmatogenous retinal detachments. There is currently no effective prevention or treatment for PVR. Platelet-derived growth factor receptor α (PDGFRα) is associated with formation of PVR in humans, and strongly promotes experimental PVR. Surprisingly, experimental PVR is driven by vitreal growth factors outside of the PDGF family. The purpose of this study was to identify those vitreal growth factors necessary for experimental PVR and establish a potential approach to prevent PVR.
Vitreous samples were obtained from experimental rabbits or patients undergoing retinal detachment repair. A panel of 21 growth factors, all of which have been implicated in PVR, were quantified in vitreous using either multiplex assays, or quantitative western immunoblotting. Those growth factors found elevated in PVR vitreous were tested for their ability to promote signaling events and cellular responses intrinsic to PVR. Antibodies and traps that neutralize the candidate growth factors were tested for their ability to prevent experimental PVR.
Neutralizing a subset of growth factors present in vitreous eliminated its ability to induce PVR-relevant signaling events and cellular responses; these include TGFα, EGF, HGF, TGF-β1, IGF-1, FGF-2, and IL-8. A single vitreal injection of antibodies and traps selective for this set of growth factors prevented PVR. We also subjected human vitreous to a similar neutralization assay. The same panel of 21 growth factors were profiled in patient PVR vitreous. Subsequent testing of their ability to induce PVR-related signaling events and cellular responses accurately identified those that were required for vitreous-induced contraction of primary RPE cells from a patient PVR membrane. The essential growth factors were nearly identical to those found in rabbits.
A set of growth factors was identified that appears important in PVR formation in the rabbits and in patients. These findings strongly support the idea that vitreal growth factors are a driving force in PVR and constitute realistic therapeutic targets.
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