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

MAGALÍ RIDANO; PAULA SUBIRADA; MARÍA C. PAZ; VALERIA LORENC; JUAN STUPIRSKI; ANA GRAMAJO; JOSE LUNA; DIEGO CROCI; GABRIEL RABINOVICH; MARÍA C. SÁNCHEZ

ONCOTARGET

Oncotarget Impact Journals

Año: 2017

1949-2553

Neovascular retinopathies are leading causes of irreversible blindness. Althoughvascular endothelial growth factor (VEGF) inhibitors have been established asthe mainstay of current treatment, clinical management of these diseases is stilllimited. As retinal impairment involves abnormal neovascularization and neuronaldegeneration, we evaluated here the involvement of galectin-1 in vascular andnon-vascular alterations associated with retinopathies, using the oxygen-inducedretinopathy (OIR) model. Postnatal day 17 OIR mouse retinas showed the highestneovascular profile and exhibited neuro-glial injury as well as retinal functional loss,which persisted until P26 OIR. Concomitant to VEGF up-regulation, galectin-1 washighly expressed in P17 OIR retinas and it was mainly localized in neovascular tufts. Inaddition, OIR induced remodelling of cell surface glycophenotype leading to exposureof galectin-1-specific glycan epitopes. Whereas VEGF returned to baseline levels atP26, increased galectin-1 expression persisted until this time period. Remarkably,although anti-VEGF treatment in P17 OIR improved retinal vascularization, neithergalectin-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-1as non-redundant independent pathways. Supporting the clinical relevance of thesefindings, we found increased levels of galectin-1 in aqueous humor from patientswith proliferative diabetic retinopathy and neovascular glaucoma. Thus, using an OIRmodel and human samples, we identified a role for galectin-1 accompanying vascularand non-vascular retinal alterations in neovascular retinopathies.