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Diabetes. 2017 Jul;66(7):1950-1956. doi: 10.2337/db16-1035. Epub 2017 Apr 11.

Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis.

Author information

1
Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
2
Universidad Pontificia Bolivariana, Medellin, Colombia.
3
C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA.
4
Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
5
Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA.
6
Center for Personalized Medicine, Children's Hospital Los Angeles, Los Angeles, CA.
7
Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA joseph_arboleda@meei.harvard.edu leo_kim@meei.harvard.edu patricia_damore@meei.harvard.edu.
8
Department of Pathology, Harvard Medical School, Boston, MA.

Abstract

Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world's working adult population and affects those with type 1 and type 2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation. Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient-derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal angiogenesis. Inhibition of RUNX1 activity with the Ro5-3335 small molecule resulted in a significant reduction of neovascular tufts in oxygen-induced retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal angiogenesis.

PMID:
28400392
PMCID:
PMC5482092
DOI:
10.2337/db16-1035
[Indexed for MEDLINE]
Free PMC Article

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