Matrix metalloproteinases and their inhibitors in vitreous in age-related macular degeneration and proliferative diabetic retinopathy

Purpose. Matrix metalloprotetnases (MMP) and their inhibitors are involved in extracelular matrix turnover and have been proposed to be involved in the pathogenesis of retinal disease such as age-related macular degeneration (AMD). Little is known about the role of these substances in human vitreous. The purpose of this study was to examine the MMPs and tissue inhibitors of metalloproteinases (TIMPs) in human vitreous in AMD, proliferate diabetic retinopathy (PDR), and normal eye bank donor eyes. Methods. Nine vitreous samples were collected at the time of vitrectomy. Of these, diagnoses included AMD (7) and PDR (2). Vitreous samples were also obtained from 16 normal fresh eye bank donor eyes as controls. All samples were centrifuged, separated from the cell pellet and stored at -80°C until the time of the experiment. SDS-PAGE, zymography, and reverse zymography were performed on the liquid vitreous. Results. A 120 kDa serine proteinase was found in 2 of the 7 AMD samples. An inhibitor of MMP activity, of a lower molecular weight than MMP-2, was found in all of the samples. An 80 kDa metalloproteinase was found in several samples, but was much more abundant in the 2 PDR samples. Conclusions. Although no strong correlation was found between MMPs of normal donor eyes and eyes of patients who have undergone vitrectomy for AMD and PDR in comparison to controls, the MMP levels found in the PDR vitreous warrant further investigation. Results of additional samples and analyses will be presented. Further characterization of these p rote in as es and their inhibitors is indicated to more fully understand their role in ophthalmic disease.

Duke Scholars

Author Cynthia Ann Toth Ophthalmology, Vitreoretinal Diseases & Surgery