Oncotarget

Research Papers:

Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF

Magali E. Ridano, Paula V. Subirada, María C. Paz, Valeria E. Lorenc, Juan C. Stupirski, Ana L. Gramajo, José D. Luna, Diego O. Croci, Gabriel A. Rabinovich and María C. Sánchez _

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Oncotarget. 2017; 8:32505-32522. https://doi.org/10.18632/oncotarget.17129

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Abstract

Magali E. Ridano1, Paula V. Subirada1, María C. Paz1, Valeria E. Lorenc1,5, Juan C. Stupirski2, Ana L. Gramajo3, José D. Luna3, Diego O. Croci2,6, Gabriel A. Rabinovich2,4 and María C. Sánchez1

1 Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina

2 Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

3 Centro Privado de Ojos Romagosa-Fundación VER, Córdoba, Argentina

4 Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

5 Department of Ophthalmology, The Johns Hopkins School of Medicine, Baltimore, MD, United States

6 Laboratorio de Inmunopatología, Instituto de Histología y Embriología de Mendoza (IHEM), CONICET, Universidad Nacional de Cuyo, Facultad de Ciencias Exactas y Naturales (FCEN), Mendoza, Argentina

Correspondence to:

María C. Sánchez, email:

Gabriel A. Rabinovich, email:

Keywords: galectin-1, neovascularization, neurodegeneration, retinopathies, vascular endothelial growth factor

Received: February 16, 2017 Accepted: March 31, 2017 Published: April 16, 2017

Abstract

Neovascular retinopathies are leading causes of irreversible blindness. Although vascular endothelial growth factor (VEGF) inhibitors have been established as the mainstay of current treatment, clinical management of these diseases is still limited. As retinal impairment involves abnormal neovascularization and neuronal degeneration, we evaluated here the involvement of galectin-1 in vascular and non-vascular alterations associated with retinopathies, using the oxygen-induced retinopathy (OIR) model. Postnatal day 17 OIR mouse retinas showed the highest neovascular profile and exhibited neuro-glial injury as well as retinal functional loss, which persisted until P26 OIR. Concomitant to VEGF up-regulation, galectin-1 was highly expressed in P17 OIR retinas and it was mainly localized in neovascular tufts. In addition, OIR induced remodelling of cell surface glycophenotype leading to exposure of galectin-1-specific glycan epitopes. Whereas VEGF returned to baseline levels at P26, increased galectin-1 expression persisted until this time period. Remarkably, although anti-VEGF treatment in P17 OIR improved retinal vascularization, neither galectin-1 expression nor non-vascular and functional alterations were attenuated. However, this functional defect was partially prevented in galectin-1-deficient (Lgals1-/-) OIR mice, suggesting the importance of targeting both VEGF and galectin-1 as non-redundant independent pathways. Supporting the clinical relevance of these findings, we found increased levels of galectin-1 in aqueous humor from patients with proliferative diabetic retinopathy and neovascular glaucoma. Thus, using an OIR model and human samples, we identified a role for galectin-1 accompanying vascular and non-vascular retinal alterations in neovascular retinopathies.


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