Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF
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 neovascula...
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todo:paper_19492553_v8_n20_p32505_Ridano2023-10-03T16:37:18Z Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF Ridano, M.E. Subirada, P.V. Paz, M.C. Lorenc, V.E. Stupirski, J.C. Gramajo, A.L. Luna, J.D. Croci, D.O. Rabinovich, G.A. Sánchez, M.C. Galectin-1 Neovascularization Neurodegeneration Retinopathies Vascular endothelial growth factor bevacizumab epitope galectin 1 glycan oxygen vasculotropin vasculotropin inhibitor animal experiment animal model animal tissue aqueous humor Article cell surface controlled study female human male molecular imprinting mouse nonhuman oxygen-induced retinopathy perinatal period phenotype proliferative retinopathy protein expression protein localization protein targeting retina blood vessel retina neovascularization signal transduction treatment response upregulation 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. © Ridano et al. Fil:Croci, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19492553_v8_n20_p32505_Ridano |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Galectin-1 Neovascularization Neurodegeneration Retinopathies Vascular endothelial growth factor bevacizumab epitope galectin 1 glycan oxygen vasculotropin vasculotropin inhibitor animal experiment animal model animal tissue aqueous humor Article cell surface controlled study female human male molecular imprinting mouse nonhuman oxygen-induced retinopathy perinatal period phenotype proliferative retinopathy protein expression protein localization protein targeting retina blood vessel retina neovascularization signal transduction treatment response upregulation |
spellingShingle |
Galectin-1 Neovascularization Neurodegeneration Retinopathies Vascular endothelial growth factor bevacizumab epitope galectin 1 glycan oxygen vasculotropin vasculotropin inhibitor animal experiment animal model animal tissue aqueous humor Article cell surface controlled study female human male molecular imprinting mouse nonhuman oxygen-induced retinopathy perinatal period phenotype proliferative retinopathy protein expression protein localization protein targeting retina blood vessel retina neovascularization signal transduction treatment response upregulation Ridano, M.E. Subirada, P.V. Paz, M.C. Lorenc, V.E. Stupirski, J.C. Gramajo, A.L. Luna, J.D. Croci, D.O. Rabinovich, G.A. Sánchez, M.C. Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF |
topic_facet |
Galectin-1 Neovascularization Neurodegeneration Retinopathies Vascular endothelial growth factor bevacizumab epitope galectin 1 glycan oxygen vasculotropin vasculotropin inhibitor animal experiment animal model animal tissue aqueous humor Article cell surface controlled study female human male molecular imprinting mouse nonhuman oxygen-induced retinopathy perinatal period phenotype proliferative retinopathy protein expression protein localization protein targeting retina blood vessel retina neovascularization signal transduction treatment response upregulation |
description |
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. © Ridano et al. |
format |
JOUR |
author |
Ridano, M.E. Subirada, P.V. Paz, M.C. Lorenc, V.E. Stupirski, J.C. Gramajo, A.L. Luna, J.D. Croci, D.O. Rabinovich, G.A. Sánchez, M.C. |
author_facet |
Ridano, M.E. Subirada, P.V. Paz, M.C. Lorenc, V.E. Stupirski, J.C. Gramajo, A.L. Luna, J.D. Croci, D.O. Rabinovich, G.A. Sánchez, M.C. |
author_sort |
Ridano, M.E. |
title |
Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF |
title_short |
Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF |
title_full |
Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF |
title_fullStr |
Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF |
title_full_unstemmed |
Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF |
title_sort |
galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-vegf |
url |
http://hdl.handle.net/20.500.12110/paper_19492553_v8_n20_p32505_Ridano |
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