CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Comparative study of VEGF inhibitors in Oxygen Induced Retinopathy (OIR) mouse model: Vascular, nonvascular and functional implications
Autor/es:
VAGLIENTI, M.V.; LUNA, J.D.; RIDANO, ME; SANCHEZ, M.C.; BARCELONA, P.F.; RABINOVICH, GA; SUBIRADA, P. V.; CROCI, D.O.; PAZ, M.C.
Lugar:
Hawaii
Reunión:
Congreso; 2018 ARVO Annual meeting; 2018
Institución organizadora:
The Association for Research in Vision and Ophtalmology (ARVO)
Resumen:
Purpose: During the past decade, vascular endothelial growth factor (VEGF) inhibitors have become standard-of-caretreatment for neovascular retinopathies. However, clinical management of these diseases is still limited. Recently, itwas demonstrated novel anti-angiogenic functions for aflibercept beyond its antagonism against VEGF familymembers. We hypothesized that aflibercept could be better than anti-VEGF therapy, improving not only vascular butalso non-vascular alterations and retinal function.Methods: The oxygen-induced retinopathy (OIR) mouse model is an excellent platform to test drugs for retinopathy ofprematurity or proliferative diabetic retinopathy. Briefly, C57BL/6 mice (OIR, N=27) were exposed to 75% O2 frompostnatal day (P) 7 to P12, after which they were brought to room air for additional five (P17) or nine days (P26).Some OIR mice were intraocular administered at P12 with 1,25 μg of bevacizumab (Anti-VEGF) (N=9), 2 μg ofaflibercept (N=9) or vehicle (N=9). At P17 and P26 mice were sacrificed. Some retinas were isolated to analyzeGlutamine Synthase (GS), Glial Fibrillary Acidic Protein (GFAP) and total caspase 3 expression by Western blots.Vascular staining at P17 with GSA isolectin B4 conjugated to Alexa 488 was also performed. Finally, retinal functionwas analyzed by electroretinography (ERG). GraphPad Prism program was employed for statistical analysis accordingto the experimental data.Results: Aflibercept therapy reduced the vascular alterations observed in the OIR mice in a similar way to anti-VEGFtreatments. The retinas of mice injected with anti-VEGF had lower levels of total caspase 3 than those injected withaflibercept. Furthermore, unlike that observed in mice injected with anti-VEGF, GFAP and GS protein expressionalterations observed in control OIR mice were reduced in mice injected with aflibercept. Finally, there were noimprovements in ERG response of mice injected with aflibercept compared to those injected with anti-VEGF and OIRcontrol miceConclusions: Aflibercept therapy showed vascular improvement in a similar way to anti-VEGF although it alsoimproved non-vascular alterations in the OIR model. However, the functional retinal damage of OIR mice was not ableto be reversed with either of these two treatments. These findings highlight the need for novel and combined therapies