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Steven Pennock, David Kim, Shizuo Mukai, Matthew Kuhnle, Dal Chun, Joanne Matsubara, Jing Cui, Patrick Ma, David Maberley, Andrius Kazlauskas; Ranibizumab is a potential prophylaxis for proliferative vitreoretinopathy, a non-angiogenic blinding disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2849.
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Proliferative vitreoretinopathy (PVR) is an example of a disease that is difficult to predict, lacks effective treatment options, and substantially reduces an individual’s quality of life. It is the primary reason that surgery to correct rhegmatogenous retinal detachment fails. 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. We sought to determine whether ranibizumab (RBZ), an anti-VEGF-A monoclonal antibody fragment, could reduce the pathogenic bioactivity of vitreous from patients and experimental animals with PVR, and whether it could protect rabbits from developing this disease.
Using cultured cells, the bioactivity of vitreous from animals and patients with PVR was assessed biochemically (by western analysis, neutralization and dose-response assays), molecularly (by knock-down experiments), and biologically (by contraction and survival assays) of cultured cells. In rabbits, experimental PVR was induced by intravitreal injection of fibroblasts.
RBZ, one of the clinically approved agents that neutralizes VEGF-A, reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The mechanism of action of RBZ involved de-repressing PDGFs, which at the concentrations present in PVR vitreous, inhibited non-PDGF-mediated activation of PDGFRα. Moreover, the ratio of VEGF-A/PDGF correlated with clinical PVR.
These pre-clinical findings suggest that currently 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.
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