INFLUENCE ON COLLAGEN-METABOLISM OF VITREOUS FROM EYES WITH PROLIFERATIVE VITREORETINOPATHY

Purpose: Proliferative vitreoretinopathy (PVR) is characterized by cel l proliferation and membrane formation on the vitreoretinal cavity of the eye. The membranes are composed of extracellular matrix, mainly co llagen type I. To explore the possible mechanisms involved in PVR memb rane formation, the authors analyzed the role of vitreous humor on col lagen turnover. Methods: The authors studied vitreous samples from ten patients with PVR and from five donor eyes (keratoplasty) as the cont rol group. Human lung fibroblasts were used to study the influence of vitreous on collagen synthesis and cell proliferation. Neutralizing an tibodies against transforming growth factor-beta(2) (TGF-beta(2)) were used to inhibit the fibroblast collagen synthesis induced by the vitr eous samples. Collagenolytic activity was analyzed in vitreous fluid u sing H-3-labeled collagen. Results: The authors found that samples obt ained from patients with PVR significantly increased collagen synthesi s (2979 +/- 963.26 versus 800 +/- 232 dpm of H-3-proline incorporated per milligram of vitreous-incubated protein; P < 0.00043), without aff ecting fibroblast replication. The collagen synthesis induced by the v itreous samples was inhibited by anti-TGF-beta(2) antibodies in both g roups (0 and 481 +/- 59 dpm of H-3-proline incorporated per milligram of vitreous-incubated protein for control and PVR samples, respectivel y). Collagenolytic activity was considerably lower in vitreous derived from PVR samples compared with the control group (19.9 +/- 20.3 versu s 234.1 +/- 19.1 mu g of degraded collagen per milligram of vitreous-i ncubated protein; P < 0.0032). Conclusion: These results suggest that a combined mechanism, including an increase of collagen synthesis medi ated at least in part by TGF-beta(2) and a decrease of collagen degrad ation, may contribute to the exaggerated deposition of collagen observ ed in PVR membranes, and that vitreous should be considered as a part of the microenvironment that is participating actively in the pathogen esis of this vitreoretinal disorder.