A novel strategy to develop therapeutic approaches to prevent proliferative vitreoretinopathy.
Proliferative vitreoretinopathy (PVR) thwarts the repair of rhegmatogenous retinal detachments. Currently, there is no effective prevention for PVR. Platelet-derived growth factor receptor α (PDGFRα) is associated with PVR in humans and strongly promotes experimental PVR driven by multiple vitreal growth factors outside the PDGF family. We sought to identify vitreal factors required for experimental PVR and to establish a potential approach to prevent PVR. Vitreous was obtained from normal rabbits or those in which PVR was either developing or stabilized. Normal vitreous contained substantial levels of growth factors and cytokines, which changed quantitatively and/or qualitatively as PVR progressed and stabilized. Neutralizing a subset of these agents in rabbit vitreous eliminated their ability to induce PVR-relevant signaling and cellular responses. A single intravitreal injection of neutralizing reagents for this subset prevented experimental PVR. To identify growth factors and cytokines likely driving PVR in humans, we subjected vitreous from patients with or without PVR to a similar series of analyses. This analysis accurately identified those agents required for vitreous-induced contraction of cells from a patient PVR membrane. We conclude that combination therapy encompassing a subset of vitreal growth factors and cytokines is a potential approach to prevent PVR.
Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Steven
S
Pennock
Marc-Andre
MA
Rheaume
Shizuo
S
Mukai
Andrius
A
Kazlauskas
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D012163:Retinal Detachment / Q000209:etiology; D015398:Signal Transduction / Q000502:physiology; D018630:Vitreoretinopathy, Proliferative / Q000517:prevention & control*; D014822:Vitreous Body / Q000737:chemistry*
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha