LACK OF GALECTIN-1 PREVENTS BIOCHEMICAL AND FUNCTIONAL ALTERATIONS IN A MOUSE MODEL OF OXYGEN-INDUCED RETINOPATHY

CROCCI D; RIDANO MAGALI E; RABINOVICH G; SUBIRADA CALDARONE PAULA; SANCHEZ MC; PAZ MC

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Abstract: Neovascular retinopathies are leading causes of irreversibleblindness. Although vascular endothelial growth factor(VEGF) inhibitors have been established as the mainstay of currenttreatment, clinical management of these diseases is still limited.Previously we showed that Galectin-1 (Gal1) is involved invascular and non-vascular alterations associated with retinopathies,using the oxygen-induced retinopathy (OIR) mouse model. Postnatalday 17 OIR mouse retinas showed the highest neovascularprofile and VEGF levels and exhibited neuro-glial injury as well asretinal functional loss, which persisted until P26 OIR. Concomitantto VEGF up-regulation, Gal1 was highly expressed in P17 OIR retinas.Whereas VEGF returned to baseline levels at P26, increasedGal1 expression persisted until this time period. Here, we evaluatedvascular and non-vascular alterations in Gal1-deficient (Lgals1-/-)OIR mice. Briefly, C57BL/6 wild type (WT) and Lgals1-/-mice wereexposed to 75% O2 from P7 to P12, after which they were brought toroom air for additional five (P17) or nine days (P26). At P17 and P26mice were sacrificed. Some eyes were fixed to obtain cryosectionsand retinas were isolated from others to analyze VEGF, glutaminesynthase (GS) and glial fibrillary acidic protein (GFAP) expressionby Western blots. Finally, retinal function was analyzed by electroretinography.GraphPad Prism program was employed for statisticalanalysis. Results showed that Lgals1-/- P17 OIR had less VEGFprotein levels than WT P17 OIR retinas. Besides, Lgals1-/- P26 OIRshowed a reduction in GFAP expression compared with WT P26OIR retinas. Moreover, Lgals1-/- OIR retinas did not show any alterationsin GS expression and the OIR retinal functional defects werepartially prevented in these mice. Thus, Gal1 play a key role in thepathogenesis of neovascular retinopathies and could be postulatedas a novel therapeutic target.