Influence on Collagen Metabolism of Vitreous from Eyes with Proliferative Vitreoretinopathy

Purpose: Proliferative vitreoretinopathy ( P VR) is characterized by cell proliferation and membrane formation on the vitreoretinal cavity of the eye. The membranes are composed of extracellular matrix, mainly collagen type I. To explore the possible mechanisms involved in PVR membrane formation, the authors analyzed the role of vitreous humor on collagen turnover. Methods: The authors studied vitreous samples from ten patients with PVR and from five donor eyes (keratoplasty) as the control group. Human lung fibroblasts were used to study the influence of vitreous on collagen synthesis and cell proliferation. Neutralizing antibodies against transforming growth factor-beta 2 (TGF-β 2 ) were used to inhibit the fibroblast collagen synthesis induced by the vitreous samples. Collagenolytic activity was analyzed in vitreous fluid using 3 H-labeled collagen. Results: The authors found that samples obtained from patients with PVR significantly increased collagen synthesis (2979 ± 963.26 versus 800 ± 232 dpm of 3Hproline incorporated per milligram of vitreous-incubated protein; P 2 antibodies in both groups (0 and 481 ± 59 dpm of 3 Hproline incorporated per milligram of vitreous-incubated protein for control and PVR samples, respectively). Collagenolytic activity was considerably lower in vitreous derived from PVR samples compared with the control group (19.9 ± 20.3 versus 234.1 ± 19.1 ,μg of degraded collagen per milligram of vitreous-incubated protein; P Conclusion: These results suggest that a combined mechanism, including an increase of collagen synthesis mediated at least in part by TGF-02 and a decrease of collagen degradation, may contribute to the exaggerated deposition of collagen observed in PVR membranes, and that vitreous should be considered as a part of the microenvironment that is participating actively in the pathogenesis of this vitreoretinal disorder.