Inhibición de la neovascularización retinal mediada por doxiciclina: estudios in vitro e in vivo

FORMICA ML; PAZ MC; SUBIRADA, PAULA V.; JORAY B; VAGLIENTI MV; BARCELONA PF; PALMA S; SANCHEZ MC

Congreso; XIII Congreso de investigaciones en Visión y Oftalmología, 28-30 octubre de 2021. Presentacion E-Poster; 2021

Objectives: With the aim of analyzing groundbreakingtherapeutics in neovascularization(NV) associated with ischemic retinal pathologies,the in-vitro and in vivo effect of doxycycline(DXC) on matrix metalloproteinases(MMPs) and retinal NV was evaluated.Materials and methods: The cytotoxicity ofDXC in Müller glial (MIO-M1) and in bovineaortic endothelial cells (BAEC) was evaluatedby MTT assay, while the effect of DXC on theenzymatic activity of MMP-2 and 9 in MIO-M1by zymography and on tube-formation assay inBAEC. In C57BL/6 WT mice, tolerance to intravitreal(iv) DXC was assessed by ERG studiesand retinal histology with H-Eo. In oxygen-inducedretinopathy (OIR) mice model, the effectof DXC (iv) on the activity and expression ofMMP-2 was evaluated in retinal homogenatesby zymography and western blot; and on retinalNV by isolectin GSA-IB4 and anti-MMP-2staining in whole mounted retina.Results: DXC presented a cytotoxicity less than20% below 60 μg/mL (MIO-M1) and 6.25 μg/mL(BAEC). In comparison to cells incubated withvehicle, DXC significantly decreased (39±3)%and (52±4)% the basal activity of MMP-2 andMMP-9 in MIO-M1, respectively; and (56±13)%the BAEC tube formation. In C57BL/6 mice, DXCdid not alter ERG parameters or retinal histology.A decreasing trend in MMP-2 activity and retinalNV was observed in OIR mice treated with DXCcompared to control group (vehicle).Conclusion: DXC, in non-cytotoxic doses,exhibited inhibitory action on the activity ofMMPs both in vitro and in the retina of OIRmice, as well as antiangiogenic properties.