Neovascularization and retinal degeneration
The Sanchez lab is focused on the area of angiogenic and neurodegenerative complications in retinopathies, including retinopathy of prematurity (ROP), the leading cause of blindness in youngsters; diabetic retinopathy (DR), the leading cause of blindness in working age adults; and age-related macular degeneration (AMD), the leading cause of blindness in the elderly.
The team has been advancing on various aspects of retinal vascular physiology as well as retinal neovascular diseases. In particular, we showed increased levels of α2-macroglobulin (α2-M) and metalloproteinases (MMPs) in the retina of animals exposed to hypoxia correlating with human vitreous samples obtained from patients with DR.
In addition, adult mice intravitreally injected withα2M increased GFAP protein expression levels and autophagic flux in Müller glial cells (MGCs). Recently, we found that the IGF-1 / IGF-1R system regulates the activity of MMP-2 also in MGCs, which has a critical role in maintaining homeostasis of extracellular medium during development as well as in angiogenic processes. While retinopathies were classically considered as a microvascular disease, it is becoming apparent that degenerative changes also occur. We are currently determining the effect of hypoxia and the α2M on the autophagy pathways with the purpose to identify novel targets that can represent potential therapies for retinopathies treatment.
I) IGF-1 regulates the extracellular level of MMP-2 active form and promotes Müller Glial Cell migration. Lorenc V, Jaldin Fincati V., Luna J., Chiabrando G. and Sánchez MC. Invest Ophthalmol Vis Sci. 2015; 56:6948–6960.
II) Animal models of diabetic retinopathy: understanding the pathogenesis and potential use in the development of new therapeutic agents. Paula V. Subirada Caldarone, Valeria E. Lorenc y Ma. Cecilia Sánchez*. Bitacora Digital 2013 Aug Vol 1, No 2 (1).
III) Activated alpha-2 macroglobulin induces via LRP1 the Müller glial cell migration by regulating the MT1-MMP activity. Pablo F. Barcelona, Javier Jaldin Fincati, María Cecilia Sánchez*, Gustavo Alberto Chiabrando*. FASEB Journal 2013 Aug;27(8):3181-97 *Corresponding authors: MC Sánchez and GA Chiabrando.
IV) Differential effects of insulin on peripheral diabetes-related changes in mitochondrial bioenergetics: involvement of advanced glycosylated end products. Aline Pertile Remor, Filipe José de Matos, Karina Ghisoni, Thiago Lenoir da Silva, Greici Eidt1, Marília Búrigo, Andreza Fabro de Bem, Paulo César Lock Silveira, Andrés de León, Maria Cecilia Sanchez, Carlos Alberto Saraiva-Gonçalves, André Quincozes-Santos, Rafael Borba Rosa, Alexandra Latini. Biochim Biophys Acta. 2011 Nov;1812(11):1460-71. Epub 2011 Jul 13.
V) α2-Macroglobulin induces glial fibrillary acidic protein mediated by LRP1 in retinal Müller cells. Barcelona PF; Ortiz SG, Chiabrando GA; Sánchez MC*. Investig. Ophthalmol. Vision Sciences 2011 Feb 9;52(2):778-86.
VI) Edema macular diabético clínicamente significativo: análisis discriminante de parámetros bioquímicos. Forzinetti GM, Collino C, Baroni MV, Ferrer D, Gramajo AL, Luna JD, Sánchez MC*. Oftalmologia Clinica y Experimental 2010 Dic; 4(3):96-102.
VII) Activated alpha2 macroglobulin induces matrix metalloproteinase 9 expression by low density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-kappaB activation in macrophage derived cell lines. Cáceres LC, Bonacci GR, Sánchez MC, Chiabrando GA. J Cell Biochem. 2010 Oct 15;111(3):607-17.
VIII) Expression and localization of Low density lipoprotein receptor-related protein 1 and α2-Macroglobulin in retinal and choroidal tissue of proliferative retinopathies”. Barcelona PF; Luna JD; Chiabrando GA; Juarez CP ; Bhutto I; Mcleod DS; Sánchez MC* and Lutty GA3*. Exp Eye Res. 2010 Aug;91(2):264-72. Corresponding authors: MC Sánchez and GA Lutty.
IX) "Insulin Induces the Low Density Lipoprotein Receptor-Related Protein (LRP-1) Degradation by the Proteasomal System in J774 Macrophage-Derived Cells." Ceschin D, Sánchez MC and Chiabrando GA. Journal of Cellular Biochemistry 2009 Feb 15;106(3):372-80.
X) “Effect of retinal laser photocoagulation on the activity of metalloproteinases and the alpha2-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy”. Sánchez MC, Luna JD, Barcelona PF, Gramajo L, Juarez PC, Riera CM, Chiabrando, GA. Experimental Eye Research (2007) 85(5):644-50.
XI) “Lipopolysaccharide (LPS) blocks the activated α2-Macroglobulin-induced MAPK-ERK1/2 phosphorylation mediated by LRP-1 in the J774 macrophage-derived cell line”. Bonacci GR,* Cáceres LC*, Sánchez MC, Chiabrando GA. Archives of Biochemistry and Biophysics (2007) 460: 100–106
XII) “Low-density lipoprotein receptor related protein-1 (LRP-1) expression in a rat model of oxygen-induced retinopathy”. Sánchez MC, Barcelona PF, Luna JD, Ortiz S, Juarez PC, Riera CM, Chiabrando GA. Experimental Eye Research 2006; 83: 1-8.
XIII) “Structural evaluation of plasma α2-Macroglobulin in acute pancreatitis”. Bisaro de Lorenc L, Ramos A, Sánchez MC, Montenegro R, Chiabrando GA. Clin Chem Lab Med. 2005;43(11):1183-9.
XIV) "Low Density Lipoprotein Receptor-Related Protein (LRP) mediates the Inhibition of NGF-Promoted Neurite-Outgrowth by Pregnancy Zone Protein and α2-Macroglobulin in PC12 Cells". Chiabrando GA, Sánchez MC, Skornicka EL, and Koo PH. Journal Neuroscience Research (2002) Oct 1;70(1):57-64.
XV) "Differential binding properties of Human Pregnancy Zone Protein- and α2-Macroglobulin-proteinase complexes to low density lipoprotein receptor-related protein (LRP)". Chiabrando G., Vides MA. and Sánchez MC̽*. Archives of Biochemistry and Biophysics (2002) Feb 1;398(1):73-8.
XVI) "Pregnancy Zone Protein-Tissue-type Plasminogen Activator Complexes Bind to Low Density Lipoprotein Receptor-related Protein (LRP)". Sanchez MC, Chiabrando GA, Vides MA. Archives of Biochemistry and Biophysics (2001) 389: 218-222
XVII) "Stabilization of homogeneous preparations of Pregnancy Zone Protein liophilized in the presence of saccharose. Structural and functional studies". Bonacci G, Sánchez C, Gonzalez M, Ceschín D, Fidelio G, Vides MA and Chiabrando G. Journal of Biochememical and Biophysical Methods (2000) 20; 46 (1-2): 95-105.
XVIII) "Interaction of Human Tissue Plasminogen Activator (t-PA) with Pregnancy Zone Protein. A Comparative Study to t-PA-α2-Macroglobulin Interaction". Sánchez MC, Chiabrando G, Guglielmone H, Bonacci G, Rabinovich G and Vides MA. Journal of Biochemistry (Tokyo) (1998) 124 (2): 274-279.
XIX) "Inhibitory effects of human α2-Macroglobulin on Trypanosoma cruzi epimastigote proteinases". Ramos A, Remedi MS, Sánchez C, Bonacci G, Vides MA and Chiabrando G. Acta Trópica (1997) 68: 327-337.
XX) "A procedure for human pregnancy zone protein (and human α2-macroglobulin) purification using hydrophobic interaction chromatography on Phenyl-Sepharose CL-4B". Chiabrando G, Bonacci G, Sánchez C, Ramos A, Zalazar F and Vides MA. Protein Expression and Purification (1997) 9: 399-406.