Miguel Flores-Bellver

Assistant Professor

University of Colorado Anschutz Medical Campus

United States

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Articles (10)

Year:

2024

Year:

2023

Year:

2023

Year:

2023

Year:

2023

Year:

2023

Year:

2023

For patients with proliferative diabetic retinopathy (PDR) who do not respond adequately to pan-retinal laser photocoagulation (PRP) or anti–vascular endothelial growth factor (VEGF) therapies, we hypothesized that vascular cells within neovascular tissue secrete autocrine/paracrine angiogenic factors that promote disease progression. To identify these factors, we performed multiplex ELISA angiogenesis arrays on aqueous fluid from PDR patients who responded inadequately to anti-VEGF therapy and/or PRP and identified plasminogen activator inhibitor-1 (PAI-1). PAI-1 expression was increased in vitreous biopsies and neovascular tissue from PDR eyes, limited to retinal vascular cells, regulated by the transcription factor hypoxia-inducible factor (HIF)-2α, and necessary and sufficient to stimulate angiogenesis. Using a pharmacologic inhibitor of HIF-2α (PT-2385) or nanoparticle-mediated RNA interference targeting Pai1 , we demonstrate that the HIF-2α/PAI-1 axis is necessary for the development of retinal neovascularization in mice. These results suggest that targeting HIF-2α/PAI-1 will be an effective adjunct therapy for the treatment of PDR patients.

Year:

2022

Year:

2022

Year:

2021

Collaborators (81)

VIKRAMSINGH GUJAR

Assistant Professor

University of Oklahoma Health Sciences Center

UNITED STATES

Miguel Flores-Bellver

Research Interests

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Articles (10)

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

Extracellular vesicles of human diabetic retinopathy retinal tissue and urine of diabetic retinopathy patients are enriched for the junction plakoglo bin protein.

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin

Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.

Expression of two major isoforms of MYO7A in the retina: Considerations for gene therapy of Usher syndrome type 1B.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice

HIF-1α accumulation in response to transient hypoglycemia may worsen diabetic eye disease.

PAI-1 is a vascular cell–specific HIF-2–dependent angiogenic factor that promotes retinal neovascularization in diabetic patients

A Surgical Kit for Stem Cell-Derived Retinal Pigment Epithelium Transplants: Collection, Transportation, and Subretinal Delivery

Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors.

Collaborators (81)

VIKRAMSINGH GUJAR

Ramaroson Andriantsitohaina

Oscar Wiklander

Pia Siljander

Elena Martens-Uzunova

Michele Zanoni

Eduardo Reátegui

Sveva Bollini

Kirsty Danielson

Anna Krasnodembskaya

Lucia Paolini

Jameel Inal

Julie Saugstad

Irina Nazarenko

Marta Garcia-Contreras

Fatemeh Momen-Heravi

Albano Caceres-Verschae

Jennifer Jones

Maiken Mellergaard

Kimberley Louise Alexander

Christian Neri

Stephen Redenti

Ann M Wehman

Lesley Cheng

Rachel Crossland

Daniel Kim

Suman Dutta

Deborah Goberdhan

FRANCESC E. BORRAS

Jason Webber

Mona Batish

Aurélie Ledreux

Tsuneya Ikezu

Cécile MALNOU

Mikael Klingeborn

John Miklavcic

Ayesha Saleem

Ole Østergaard

Michael P Rimmer

Mathilde Mosser

Sigrun Lange

Manuel Varas-Godoy

Kenny Man

Somchai Chutipongtanate

Benedetta Bussolati

Janis A Müller

Richard Chahwan

Marzena Kurzawa-Akanbi

Annalisa RADEGHIERI

Martin van Royen

Naveed Akbar

Akrit Sodhi

Riccardo Natoli

Christian P. Pallasch

Ming-Wen Hu

Elisa Tonoli

Irma Schabussova

Meike Saul

Orazio Fortunato

Juhee Park

Kerstin Menck

Carolina Soekmadji

Owen Davies

Katrin Reiners