Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis.
Jonathan D Lam, Daniel J Oh, Lindsay L Wong, Dhanesh Amarnani, Cindy Park-Windhol, Angie V Sanchez, Jonathan Cardona-Velez, Declan McGuone, Anat O Stemmer-Rachamimov, Dean Eliott, Diane R Bielenberg, Tave van Zyl, Lishuang Shen, Xiaowu Gai, Patricia A D'Amore, Leo A Kim, Joseph F Arboleda-Velasquez
Author Information
Jonathan D Lam: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Daniel J Oh: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Lindsay L Wong: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Dhanesh Amarnani: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Cindy Park-Windhol: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Angie V Sanchez: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Jonathan Cardona-Velez: Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Declan McGuone: C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA.
Anat O Stemmer-Rachamimov: C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA.
Dean Eliott: Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Diane R Bielenberg: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Tave van Zyl: Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Lishuang Shen: Center for Personalized Medicine, Children's Hospital Los Angeles, Los Angeles, CA.
Xiaowu Gai: Center for Personalized Medicine, Children's Hospital Los Angeles, Los Angeles, CA.
Patricia A D'Amore: 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.
Leo A Kim: 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.
Joseph F Arboleda-Velasquez: 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.
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.
References
Invest Ophthalmol Vis Sci. 2012 Dec 03;53(13):7912-27
[PMID: 23092923]
