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Matrix metalloproteinase-9 expression in retinal ganglion cell layer and effect of topically applied brimonidine tartrate 0.2% therapy on this expression in an endothelin-1-induced optic nerve ischemia model

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Abstract

The purpose of this research is to investigate the expression of matrix metalloproteinase-9 (MMP-9) in retinal ganglion cells (RGC) and the impact of topically applied brimonidine tartrate 0.2% (BMD) on this expression in an endothelin-1 (ET-1)-induced chronic optic nerve (ON) ischemia model of rabbit. Osmotically driven minipumps were implanted in one eye of 16 New Zealand albino rabbits to deliver ET-1 at the constant rate of 0.5 μl/h for 2 weeks. ET-1 was given with (group 3) and without topical BMD therapy (group 1). Groups 2 and 4 were taken as controls. MMP-9 expression by immunohistochemically and proportion of cells undergoing apoptosis in RGC layer were investigated. The correlation between the MMP-9 immunopositivity and the proportion of cells undergoing apoptosis in the RGC layer was evaluated. MMP-9 immunopositivity was found to be significantly higher in both groups 1 and 3 compared to that of the controls. There was no difference between groups 1 and 3 regarding MMP-9 expression (p = 0.495). A positive correlation was found between the proportion of cells undergoing apoptosis and MMP-9 expressions in the RGC layer in group 1 (p = 0.031, r = 0.754). MMP-9 expression in the RGC layer seems to significantly increase in the ET-1-induced chronic ON ischemia model. Topical BMD therapy does not seem to affect this MMP-9 expression.

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References

  1. Sommer A (1989) Intraocular pressure and glaucoma. Am J Ophthalmol 107:186–188

    CAS  PubMed  Google Scholar 

  2. Flammer J, Orgül S, Costa VP et al (2002) The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 21:359–393

    Article  PubMed  Google Scholar 

  3. Hernandez MR (2000) The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res 19:297–321

    Article  CAS  PubMed  Google Scholar 

  4. Prasanna G, Krishnamoorthy R, Clark AF et al (2002) Human optic nerve head astrocytes as a target for endothelin-1. Invest Ophthalmol Vis Sci 43:2704–2713

    PubMed  Google Scholar 

  5. Sugiyama T, Moriya S, Oku H et al (1995) Association of endothelin-1 with normal tension glaucoma: clinical and fundamental studies. Surv Ophthalmol 39(Suppl 1):S49–S56

    Article  PubMed  Google Scholar 

  6. Yan X, Tezel G, Wax MB et al (2000) Matrix metalloproteinases and tumor necrosis factor alpha in glaucomatous optic nerve head. Arch Ophthalmol 118:666–673

    CAS  PubMed  Google Scholar 

  7. He S, Prasanna G, Yorio T (2007) Endothelin-1 mediated signaling in the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in astrocytes. Invest Ophthalmol Vis Sci 48:3737–3745

    Article  PubMed  Google Scholar 

  8. Vidal-Sanz M, Lafuente MP, Sobrado-Calvo P (2000) Death and neuroprotection of retinal ganglion cells after different types of injury. Neurotox Res 2:215–227

    Article  CAS  PubMed  Google Scholar 

  9. Guo L, Moss SE, Alexander RA et al (2005) Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix. Invest Ophthalmol Vis Sci 46:175–182

    Article  PubMed  Google Scholar 

  10. Chintala SK, Zhang X, Austin JS et al (2002) Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation. J Biol Chem 277:47461–47468

    Article  CAS  PubMed  Google Scholar 

  11. Cussac D, Schaak S, Denis C et al (2002) α2B − Adrenergic receptor activates MAPK via a pathway involving arachidonic acid metabolism, matrix metalloproteinases and epidermal growth factor receptor transactivation. J Biol Chem 277:19882–19888

    Article  CAS  PubMed  Google Scholar 

  12. Aktas Z, Gurelik G, Akyurek N et al (2007) Neuroprotective effect of topically applied brimonidine tartrate 0.2% in endothelin-1-induced optic nerve ischaemia model. Clin Experiment Ophthalmol 35:527–534

    Article  PubMed  Google Scholar 

  13. Cioffi GA, Van Buskirk EM (1994) Microvasculature of the anterior optic nerve. Surv Ophthalmol 38:S107–S117

    Article  PubMed  Google Scholar 

  14. Cioffi GA, Orgul S, Onda E et al (1995) An in vivo model of chronic optic nerve ischemia: the dose-dependent effects of endothelin-1 on the optic nerve microvasculature. Curr Eye Res 14:1147–1153

    Article  CAS  PubMed  Google Scholar 

  15. Matrisian LM (1992) The matrix-degrading metalloproteinases. Bioessays 14:455–463

    Article  CAS  PubMed  Google Scholar 

  16. Oku H, Sugiyma T, Kojima S et al (1999) Experimental optic cup enlargement caused by endothelin-1-induced chronic optic nerve head ischemia. Surv Ophthalmol 44(Suppl 1):S74–S84

    Article  PubMed  Google Scholar 

  17. Chauhan BC, LeVatte TL, Jollimore CA et al (2004) Model of endothelin-1-induced chronic optic neuropathy in rat. Invest Ophthalmol Vis Sci 45:144–152

    Article  PubMed  Google Scholar 

  18. Pang IH, Yorio T (1997) Ocular actions of endothelins. Proc Soc Exp Biol Med 215:21–34

    CAS  PubMed  Google Scholar 

  19. Yorio T, Krishnamoorthy R, Prasanna G (2002) Endothelin: is it a contributor glaucoma pathophysiology? J Glaucoma 11:259–270

    Article  PubMed  Google Scholar 

  20. Stokely ME, Brady ST, Yorio T (2002) Effects of ET-1 on components of anterograde axonal transport in optic nerve. Invest Ophthalmol Vis Sci 43:3223–3230

    PubMed  Google Scholar 

  21. Bouloumie A, Planat V, Devedjian JC et al (1994) Alpha 2-adrenergic stimulation promotes preadipocyte proliferation. Involvement of mitogen-activated protein kinases. J Biol Chem 269:30254–30259

    CAS  PubMed  Google Scholar 

  22. Ouigley HA, Nickells RW, Kerrigan LA et al (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:774–786

    Google Scholar 

  23. Werb Z (1997) ECM and cell surface proteolysis: regulating cellular ecology. Cell 91:439–442

    Article  CAS  PubMed  Google Scholar 

  24. Asahi M, Sumii T, Fini ME et al (2001) Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal ischemia. Neuroreport 12:3003–3007

    Article  CAS  PubMed  Google Scholar 

  25. Wang X, Jung J, Asahi M et al (2000) Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20:7037–7042

    CAS  PubMed  Google Scholar 

  26. Zhou RH, Yan H, Wang BR et al (2007) Role of extracellular-signal regulated kinase in glutamate-stimulated apoptosis of rat retinal ganglion cells. Curr Eye Res 32:233–239

    Article  CAS  PubMed  Google Scholar 

  27. Luo JM, Cen LP, Zhang XM et al (2007) PI3K/akt, JAK/STAT and MEK/ERK pathway inhibition protects retinal ganglion cells via different mechanisms after optic nerve injury. Eur J Neurosci 26:828–842

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by Gazi University Department of Scientific Investigation Grant No: 1/2003-25.

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Authors and Affiliations

  1. Department of Ophthalmology, Gazi University Medical Faculty, Ankara, Turkey

    Zeynep Aktas, Gokhan Gurelik, Merih Önol & Berati Hasanreisoğlu

  2. Department of Pathology, Gazi University Medical Faculty, Ankara, Turkey

    Pınar Uyar Göçün & Nalan Akyürek

  3. Barış Sitesi, 59. Sokak, No: 7, Eskişehir Yolu, Ankara, Turkey

    Zeynep Aktas

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  1. Zeynep Aktas
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  2. Gokhan Gurelik
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  3. Pınar Uyar Göçün
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  4. Nalan Akyürek
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  5. Merih Önol
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  6. Berati Hasanreisoğlu
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Correspondence to Zeynep Aktas.

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Aktas, Z., Gurelik, G., Göçün, P.U. et al. Matrix metalloproteinase-9 expression in retinal ganglion cell layer and effect of topically applied brimonidine tartrate 0.2% therapy on this expression in an endothelin-1-induced optic nerve ischemia model. Int Ophthalmol 30, 253–259 (2010). https://doi.org/10.1007/s10792-009-9316-9

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  • DOI: https://doi.org/10.1007/s10792-009-9316-9

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