Evidence mapPaperPMID 40230413Full record

ArticleFrontiers in cell and developmental biology2025

Doxycycline inhibits MMP-2 retinal activity and modulates the angiogenic process

María Lina Formica, María Constanza Paz, María Victoria Vaglienti, Paula Virginia Subirada, Yamila Fernández, Mariana Belén Joray, José Domingo Luna, Pablo Federico Barcelona, Santiago Daniel Palma, María Cecilia Sánchez

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Article in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

María Lina Formica *Conicet y Departamento de Ciencias Farmacéuticas, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
María Constanza Paz *Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.
María Victoria VaglientiConsejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.
Paula Virginia SubiradaConsejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.
Yamila FernándezConsejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.
Mariana Belén JorayCentro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Católica de Córdoba (UCC), Córdoba, Argentina.
José Domingo LunaDepartamento de Vitreo-Retina, Centro Privado de Ojos Romagosa S.A, Córdoba, Argentina.
Pablo Federico BarcelonaConsejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.
Santiago Daniel Palma *Conicet y Departamento de Ciencias Farmacéuticas, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
María Cecilia Sánchez *Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Vascular endothelial growth factor (VEGF) inhibition is currently the first-line therapy for various retinal vascular disorders, however there is a strong need to develop novel therapies to target other molecules involved in the angiogenic process. In addition to well-known antibiotic properties, Doxycycline (DXC) has versatile non-antibiotic properties, therefore, our goal was to evaluate the effect of DXC on matrix metalloproteinase-2 (MMP-2) as a potential therapeutic alternative for retinal neovascularization (NV), using vascular and glial cells and the oxygen-induced retinopathy (OIR) mouse model. Methods: MGC and BAEC viability under DXC treatment was evaluated using an MTT assay. Changes of Pro MMP-2 and MMP-2 activity were measured by gelatin zymography assay in MIO-M1 cells incubated with DXC under normoxia and hypoxic conditions. VEGF-induced angiogenesis was assessed by tube formation assay in BAEC incubated with DXC for 24 h C57BL/6 mice exposed to OIR model, were intravitreally injected with a single dose of DXC at post-natal day (P)12 and retinas evaluated at P17. Results: DXC significantly decreased pro MMP-2 and MMP-2 activity in MIO-M1 supernatants and increased hypoxic-induced mRNA expression of pigmentary epithelium-derived factor (PEDF). Moreover, DXC inhibited the VEGF-induced tube formation in endothelial cells. A single intraocular administration of DXC at postnatal day (P) 12 showed a significant decrease of pro MMP-2 and MMP-2 activity together with a reduced NV and vaso-obliteration in P17 mouse retinas of OIR eyes, while no significant difference was observed neither in MMP-2 nor in VEGF protein expression. Discussion: Our results lead to propose a possible DXC mechanism for inhibition of angiogenesis through the modulation of MMPs involving the VEGF/PEDF balance. These findings underscore the potential repositioning of DXC as a new possibility for treating ocular proliferative diseases.

Indexed as

doxycyclinematrix metalloproteinasesneovascularizationoxygen-induced retinopathypigmentary epithelium-derived factorvascular endothelial growth factor

Identifiers

PMID40230413
PMCPMC11994896

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.