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Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis
Jonathan D Lam1, Daniel J Oh1, Lindsay L Wong1
1Department of Ophthalmology, Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Diabetes
|April 13, 2017
Summary
Runt-related transcription factor 1 (RUNX1) is upregulated in proliferative diabetic retinopathy (PDR). Inhibiting RUNX1 reduces abnormal blood vessel growth, offering a potential new treatment for PDR-induced blindness.
Area of Science:
- Ophthalmology
- Vascular Biology
- Molecular Biology
Background:
- Proliferative diabetic retinopathy (PDR) is a leading cause of blindness in working adults.
- PDR is characterized by aberrant retinal angiogenesis (new blood vessel formation).
- The molecular mechanisms driving PDR angiogenesis require further elucidation.
Purpose of the Study:
- To identify key molecular players in PDR angiogenesis.
- To investigate the role of Runt-related transcription factor 1 (RUNX1) in PDR.
- To assess the therapeutic potential of targeting RUNX1 for PDR.
Main Methods:
- Transcriptomic analysis of human PDR fibrovascular membranes (FVMs).
- In vitro studies using human retinal microvascular endothelial cells (HRMECs) under high glucose conditions.
- Immunohistochemical staining of human FVMs and mouse oxygen-induced retinopathy (OIR) models.
- Pharmacological inhibition of RUNX1 using Ro5-3335 in the OIR model.
Main Results:
- RUNX1 was identified as upregulated in CD31+ vascular endothelial cells from human PDR FVMs.
- High glucose increased RUNX1 expression in HRMECs; RUNX1 inhibition impaired HRMEC migration, proliferation, and tube formation.
- RUNX1 was detected in vessels of human FVMs and angiogenic tufts in OIR mice.
- Inhibition of RUNX1 significantly reduced neovascular tufts in the OIR model.
Conclusions:
- RUNX1 upregulation is a key feature of aberrant retinal angiogenesis in PDR.
- RUNX1 plays a critical role in regulating endothelial cell functions essential for neovascularization.
- Targeting RUNX1 presents a promising therapeutic strategy for treating PDR.