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C. Nucci, R. Russo, F. Cavaliere, G. Varano, L. Rombola', L. Morrone, G. Bagetta, M. Corasaniti; Involvement of Matrix Metalloproteinases (MMPs) 2 and 9 in Retinal Ganglion Cells (RGCs) Death Induced by Retinal Ischemia/Reperfusion. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4713.
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Matrix metalloproteinases (MMPs) belong to a family of proteolytic enzymes endowed with a remodeling function of the extracellular matrix (ECM). Up-regulation of MMPs has recently been implicated in the pathogenesis of inflammatory as well as neurodegenerative disorders including brain ischemia, Alzheimer’s disease, multiple sclerosis and HIV-associated dementia (see Yong et al., 2005, Nat Rev Neurosci; 6: 931-944).
Here we investigated the role of MMP-2 and 9 in an experimental model of acute glaucoma induced in rat by transient raise (50 min) of intraocular pressure (IOP) followed by delayed loss of retinal ganglion cells (RGCs) (see Osborne et al., 2004, Prog Ret Eye Res; 23:91-147).
Retinal ischemia was induced in adult Wistar rats by 50 min elevation of IOP (120mmHg; see Osborne et al., 2004, Prog Ret Eye Res; 23:91-147). Expression and activity of MMP-2 and -9 were studied by gelatin zymogram and in situ zymography.
Standard zymography technique demonstrated that transient retinal ischemia followed by 6h reperfusion enhances MMP-2 and -9 expression in the ischemic as compared to control retina of the fellow eye. In situ zymography revealed that gelatinolytic activity is evident after 24 h of reperfusion in the innermost part of the retina and, in particular, in the ganglion cell layer (GCL). Histologic examination showed that intravitreal administration of GM6001 (64 nmol/ 5 µl; n=3), a specific MMPs inhibitor, minimized RGCs loss typically observed after 24h reperfusion (ischemia/reperfusion= 25.50+0.29 vs GM6001= 32.34+0.33 RGCs/microscope field).
our data support the deduction that inhibition of proteolytic activity of MMP-2 and -9 may represent a target for the development of a novel therapeutic approach to prevent RGCs death.
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