Doxycycline-mediated inhibition of retinal neovascularization: studies in vitro and in vivo

FORMICA, ML; PAZ, MARÍA C.; SUBIRADA, PAULA V.; JORAY, B.; VAGLIENTI, MARIA V.; BARCELONA, PABLO F.; LUNA PINTO, JD; PALMA, S; SÁNCHEZ, MARÍA C.

Virtual

Congreso; XIII CONGRESO NACIONAL DE INVESTIGACIÓN EN VISIÓN Y OFTALMOLOGÍA; 2021

Asociación de Investigación en Visión y Oftalmología (AIVO), Capítulo International Afiliado de ARVO (The Association for Research in Vision and Ophthalmology)

Objectives: With the aim of analyzing groundbreaking therapeutics 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 of DXC in Müller glial (MIO-M1) and in bovine aortic endothelial cells (BAEC) was evaluated by MTT assay, while the effect of DXC on the enzymatic activity of MMP-2 and 9 in MIO-M1 by zymography and on tube-formation assay in BAEC. In C57BL/6 WT mice, tolerance to intravitreal (iv) DXC was assessed by ERG studies and retinal histology with H-Eo. In oxygen-induced retinopathy (OIR) mice model, the effect of DXC (iv) on the activity and expression of MMP-2 was evaluated in retinal homogenates by zymography and western blot; and on retinal NV by isolectin GSA-IB4 and anti-MMP-2 staining in whole mounted retina. Results: DXC presented a cytotoxicity less than 20% below 60 μg/mL (MIO-M1) and 6.25 μg/mL (BAEC). In comparison to cells incubated with vehicle, DXC significantly decreased (39 ±3) % and (52 ±4) % the basal activity of MMP-2 and MMP-9 in MIO-M1, respectively; and (56 ±13) % the BAEC tube formation. In C57BL/6 mice, DXC did not alter ERG parameters or retinal histology. A decreasing trend in MMP-2 activity and retinal NV was observed in OIR mice treated with DXC compared to control group (vehicle). Conclusion: DXC, in non-cytotoxic doses, exhibited inhibitory action on the activity of MMPs both in-vitro and in the retina of OIR mice, as well as antiangiogenic properties.