title: Ranibizumab is a potential prophylaxis for proliferative vitreoretinopathy, a nonangiogenic blinding disease.
abstract: Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina. Three classes of growth factors [vascular endothelial growth factor A (VEGF-A), platelet-derived growth factors (PDGFs), and non-PDGFs (growth factors outside of the PDGF family)] are relevant to PVR pathogenesis because they act on PDGF receptor α, which is required for experimental PVR and is associated with this disease in humans. We discovered that ranibizumab (a clinically approved agent that neutralizes VEGF-A) reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The apparent mechanism of ranibizumab action involved derepressing PDGFs, which, at the concentrations present in PVR vitreous, inhibited non-PDGF-mediated activation of PDGF receptor α. These preclinical findings suggest that available approaches to neutralize VEGF-A are prophylactic for PVR, and that anti-VEGF-based therapies may be effective for managing more than angiogenesis- and edema-driven pathological conditions.
authors.affiliation: The Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, and the Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Pennock
authors.forename: David
authors.initials: D
authors.lastname: Kim
authors.forename: Shizuo
authors.initials: S
authors.lastname: Mukai
authors.forename: Matthew
authors.initials: M
authors.lastname: Kuhnle
authors.forename: Dal W
authors.initials: DW
authors.lastname: Chun
authors.forename: Joanne
authors.initials: J
authors.lastname: Matsubara
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Patrick
authors.initials: P
authors.lastname: Ma
authors.forename: David
authors.initials: D
authors.lastname: Maberley
authors.forename: Arif
authors.initials: A
authors.lastname: Samad
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Van Geest
authors.forename: Sarit L
authors.initials: SL
authors.lastname: Oberstein
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
authors.forename: Andrius
authors.initials: A
authors.lastname: Kazlauskas
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001766:Blindness / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D002460:Cell Line; D004198:Disease Susceptibility / Q000473:pathology; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D011817:Rabbits; D000069579:Ranibizumab; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000069579:Ranibizumab