Role of MMP-9 in Diabetic Retinopathy
Diabetic retinopathy is a common neurovascular complication of diabetic that strike a third of diabetic patients worldwide. Complex mechanism of biomolecules including enzyme and cytokines is related to oxidative stress of constant hyperglycaemia. Vascular permeability damage resulting from endothelial leakage and apoptosis of Muller cell is the main mechanism of retinal damage. MMPs as endopeptidases have an important role in angiogenesis process of retinopathy by working with various molecules of growth factors, chemokines, cytokines and cell adhesion molecules. MMP-9 has been widely shown to be associated with inflammation, blood-retinal barrier disruption, cell apoptosis and neovascularization in the diabetic retinopathy pathomechanism.
Keywords: Diabetic retinopathy; MMP; MMP-9; Blood-retinal barrier
2. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis [Internet]. 2015; 2(1):1–25. Available from: http://dx.doi.org/10.1186/s40662-015-0026-2
3. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract [Internet]. 2018; 138:271–81. Available from: https://doi.org/10.1016/j.diabres.2018.02.023
4. Jenkins AJ, Joglekar M V., Hardikar AA, Keech AC, O’Neal DN, Januszewski AS. Biomarkers in diabetic retinopathy. Rev Diabet Stud. 2015; 12(1–2):159–95.
5. Kowluru RA. Role of matrix metalloproteinase-9 in the development of diabetic retinopathy and its regulation by H-Ras. Investig Ophthalmol Vis Sci. 2010; 51(8):4320–6.
6. Kowluru RA, Mohammad G, Dos Santos JM, Zhong Q. Abrogation of MMP-9 gene protects against the development of retinopathy in diabetic mice by preventing mitochondrial damage. Diabetes. 2011; 60(11):3023–33.
7. Chen Y, Wang W, Liu F, Tang L, Tang R, Li W. Apoptotic effect of mtrix metalloproteinases 9 in the development of diabetic retinopathy. Int J Clin Exp Pathol. 2015; 8(9):10452–9.
8. Giebel SJ, Menicucci G, McGuire PG, Das A. Matrix metalloproteinases in early diabetic retinopathy and their role in alternation of the blood-retinal barrier. Lab Investig. 2005; 85(5):597–607.
9. Opdenakker G, Abu El-Asrar A. Metalloproteinases mediate diabetes-induced retinal neuropathy and vasculopathy. Cell Mol Life Sci [Internet]. 2019; 76(16):3157–66. Available from: https://doi.org/10.1007/s00018-019-03177-3
10. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012; 366:1227–39.
11. Altmann C, Schmidt MHH. The role of microglia in diabetic retinopathy: Inflammation, microvasculature defects and neurodegeneration. Int J Mol Sci. 2018;
12. Gardner TW, Davila JR. The Neurovascular Unit and the Pathophysiologic Basis of Diabetic Retinopathy. Graefes Arch Clin Exp Ophtalmol. 2017; 255(1):1–6.
13. Flaxel CJ, Adelman RA, Bailey ST, Fawzi A, Lim JI, Vemulakonda GA, et al. Diabetic Retinopathy Preferred Practice Pattern®. Ophthalmology. 2020; 127(1):P66–145.
14. Kilpatrick ES, Rigby AS, Atkin SL, Frier BM. Does severe hypoglycaemia influence microvascular complications in Type1 diabetes? An analysis of the Diabetes Control and Complications Trial database. Diabet Med. 2012; 29(9):1195–8.
15. Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 2005; 54(6):1615–25.
16. Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI insight. 2017; 2(14):1–13.
17. Rübsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy. Int J Mol Sci. 2018; 19(4):1–31.
18. Altmanc C, Schmidt MH. the role of microglia in Diabetic Retinopathy : inflammation, microvasculature defect and neurodegeneration. Int J Mol Sci. 2018; 19.
19. Kaur C, Rathnasamy G, Foulds WS, Ling E-A. Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries. J Neurol Exp Neurosci. 2015; 10–9.
20. Cauwe B, Steen PEV Den, Opdenakker G. The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Vol. 42, Critical Reviews in Biochemistry and Molecular Biology. 2007. 113–185 p.
21. Simó R, Sundstrom JM, Antonetti DA. Ocular anti-VEGF therapy for diabetic retinopathy: The role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care. 2014; 37(4):893–9.
22. Parks WC, Wilson CL, López-Boado YS. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol. 2004; 4(8):617–29.
23. Toriseva M, Kähäri VM. Proteinases in cutaneous wound healing. Cell Mol Life Sci. 2009; 66(2):203–24.
24. Kessenbrock K, Placks V, Werb Z. Matrix Metalloproteinases: Regulators of the Tumor Microenvironment. Cell. 2015 Feb; 135(2):612–5.
25. Cui N, Hu M, Khalil RA, Mol P, Transl B, Author S. Biochemical and Biological Attributes of Matrix Metalloproteinases HHS Public Access Author manuscript. Prog Mol Biol Transl Sci [Internet]. 2017; 147(617):1–73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430303/pdf/nihms856854.pdf
26. Nissinen L, Kähäri V-M. Matrix metalloproteinases in inflammation. Biochim Biophys Acta - Gen Subj. 2014; 1840(8):2571–80.
27. Djuric T, Zivkovic M. Overview of MMP Biology and Gene Associations in Human DIseases. In: Intech [Internet]. Belgrade; 2017. p. 3–35. Available from: https://www.intechopen.com/books/advanced-biometric-technologies/liveness-detection-in-biometrics
28. Jobin PG, Butler GS, Overall CM. New intracellular activities of matrix metalloproteinases shine in the moonlight. Biochim Biophys Acta - Mol Cell Res [Internet]. 2017; 1864(11):2043–55. Available from: http://dx.doi.org/10.1016/j.bbamcr.2017.05.013
29. Cauwe B, Martens E, Proost P, Opdenakker G. Multidimensional degradomics identifies systemic autoantigens and intracellular matrix proteins as novel gelatinase B/MMP-9 substrates. Integr Biol. 2009; 1(5–6):404–26.
30. Cummins PM. Occludin: One Protein, Many Forms. Mol Cell Biol. 2012; 32(2):242–50.
31. Abu El-Asrar AM, Mohammad G, Nawaz MI, Siddiquei MM, Van Den Eynde K, Mousa A, et al. Relationship between vitreous levels of matrix metalloproteinases and vascular endothelial growth factor in proliferative diabetic retinopathy. PLoS One. 2013; 8(12):1–11.
32. Jayashree K, Yasir M, Senthilkumar GP, Ramesh Babu K, Mehalingam V, Mohanraj PS. Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy. Diabetes Metab Syndr Clin Res Rev [Internet]. 2018; 12(6):869–73. Available from: https://doi.org/10.1016/j.dsx.2018.05.006
33. De Groef L, Andries L, Lemmens K, Van Hove I, Moons L. Matrix metalloproteinases in the mouse retina: A comparative study of expression patterns and MMP antibodies Retina. BMC Ophthalmol [Internet]. 2015;15(1):1–16. Available from: http://dx.doi.org/10.1186/s12886-015-0176-y
34. Chen YD, Xu X, Xia X, Wu H, Liu K, Zheng Z, et al. MMP9 is involved in glycation end-products induced increase of retinal vascular permeability in rats and the therapeutic effect of minocycline. Curr Eye Res. 2008;33(11–12):977–83.
35. Kowluru RA, Mishra M. Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy [Internet]. 1st ed. Vol. 148, Progress in Molecular Biology and Translational Science. Elsevier Inc.; 2017. 67–85 p. Available from: http://dx.doi.org/10.1016/bs.pmbts.2017.02.004
36. Kowluru RA, Zhong Q, Santos JM. Matrix metalloproteinases in diabetic retinopathy: potential role of MMP-9. Expert Opin Investig Drugs [Internet]. 2012; 21(6):797–805. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
37. Hannocks MJ, Zhang X, Gerwien H, Chashchina A, Burmeister M, Korpos E, et al. The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes. Matrix Biol [Internet]. 2019;75–76:102–13. Available from: https://doi.org/10.1016/j.matbio.2017.11.007
38. Ghulam Mohammad, Kowluru RA. Diabetic Retinopathy and Signaling Mechanism for Activation of Matrix Metalloproteinase-9. J Cell Physiol [Internet]. 2012; 227(3):1052–61. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
39. Santos JM, Tewari S, Lin JY, Kowluru RA. Interrelationship between activation of matrix metalloproteinases and mitochondrial dysfunctiom in the development of diabetic retinopathy. Biochem Biophys Res Commun [Internet]. 2013; 438(4):1–12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
40. Tewari S, Santos JM, Kowluru RA. Damaged mitochondrial DNA replication system and the development of diabetic retinopathy. Antioxidants Redox Signal. 2012; 17(3):492–504.
41. Di Y, Nie QZ, Chen XL. Matrix metalloproteinase-9 and vascular endothelial growth factor expression change in experimental retinal neovascularization. Int J Ophthalmol. 2016; 9(6):804–8.
42. Tuuminen R, Loukovaara S. High intravitreal TGF-β1 and MMP-9 levels in eyes with retinal vein occlusion. Eye. 2014; 28(9):1095–9.
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