April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Involvement of Matrix Metalloproteinases (MMPs) 2 and 9 in Retinal Ganglion Cells (RGCs) Death Induced by Retinal Ischemia/Reperfusion
Author Affiliations & Notes
  • C. Nucci
    Ophthalmology, Univ of Rome Tor Vergata, Rome, Italy
  • R. Russo
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • F. Cavaliere
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • G. Varano
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • L. Rombola'
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • L. Morrone
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
  • G. Bagetta
    Pharmaco-Biology, University of Calabria, Cosenza, Italy
    UCADH, Sect. Neuropharmacol. Norm. Pathol. Neur. Plasticity, Arcavacata di Rende (CS), Italy
  • M. Corasaniti
    Pharmacobiological Sci, University Magna Graecia, Catanzaro, Italy
  • Footnotes
    Commercial Relationships  C. Nucci, None; R. Russo, None; F. Cavaliere, None; G. Varano, None; L. Rombola', None; L. Morrone, None; G. Bagetta, None; M. Corasaniti, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4713. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Introduction: : 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).

Purpose: : 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).

Methods: : 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.

Results: : 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).

Conclusions: : 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.

Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • ischemia • apoptosis/cell death 
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