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S. Pennock, M. Kuhnle, D. W. Chun, A. Kazlauskas; Characterization of the Vitreal Factors Associated With PVR Pathology and Severity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2711.
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Proliferative vitreoretinopathy (PVR) remains a serious obstacle to patients recovering from retinal detachments caused by ocular trauma. Apart from surgical interventions, there is currently no effective treatment for PVR. The cellular mechanisms behind PVR are poorly understood, though a variety of vitreal growth factors have been implicated in the development and pathology of this disease. The purpose of this study was to precisely determine the vitreal growth factors associated with PVR and to identify those correlating with disease severity.
We chose to investigate a panel of 22 growth factors in the vitreous of patients with retinal detachment, vitreous hemorrhage, trauma, PVR, and controls. Multiplex methodology or quantitative western immunoblotting was used to quantify the vitreal level of these agents. We also investigated the extent of PDGF-C processing/activation and the proteases (plasmin and/or TPA) responsible. Both rabbit and clinical PVR vitreous samples were used in this investigation.
Of the 22 growth factors investigated, 9 were significantly elevated in the vitreous of patients suffering PVR compared to non-PVR samples: FGF-2, G-CSF, IFNγ, IL-6, IL-8, VEGF, TGF-β1, TGF-β3, and PDGF-C. Interestingly, we also detected differences in growth factor levels between severe (e.g. trauma-induced) and non-severe PVR samples. When we looked at PDGF-C processing, PDGF-C was processed to a greater extent in PVR vitreous compared to non-PVR vitreous. As expected, plasmin was the essential processing protease of PDGF-C in PVR vitreous, and was absent in non-PVR vitreous. Surprisingly, it appeared that less PDGF-C was processed by plasmin in vitreous from patients with severe (i.e. traumatic) PVR compared to patients with less severe PVR, and this correlated to a lower level of the protease.
The presence of many of our candidate growth factors at physiological levels in PVR vitreous suggest that multiple stimuli contribute to the pathology of this disease. In particular, certain growth factors were elevated in the vitreous of patients with severe PVR compared to non-severe PVR. Specific investigation of PDGF-C, the most prevalent growth factor among those investigated, revealed that this growth factor was processed primarily by plasmin in the vitreous of patients with less severe PVR. In the small set of vitreal samples taken from patients with severe PVR, proteases in addition to plasmin appeared to be working to process PDGF-C. Taken together these results suggest different mechanisms exist in the pathology of the trauma-induced form of PVR.
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