Noting that Proliferative Diabetic retinopathy (PDR) affects those with Type 1 and 2 diabetes is a common cause of blindness in the developed world, says researchers from Schepens Eye Research Institute in Boston and colleagues examined the role of RUNX1 in PDR.
Researchers identified RUNX1 as a gene that was upregulated in CD31+ vascular endothelial cells obtained via transcriptomic analysis form human PDR Fibrovascular Membranes (FVM). Increased RUNX1 RNA and protein expression were seen in response to high glucose in in-vitro studies using human retinal microvascular endothelial cells (HRMECs) HRMECs migration, proliferation, and tube formation were reduced with RUNX1 inhibition.
Using, immunohistochemical staining for RUNX1, reactivity was seen in vessels of patient-derived FVM and angiogenic tufts in the retina of mice with oxygen-induced retinopathy. Use of the Ro5-3335 small molecule to inhibit RUNX1 activity resulted in significant reduction of neovascular tufts in oxygen-induced retinopathy.
These findings, including the high glucose-dependent expression of RUNX1, identify a novel pathway of potential therapeutic interest, and implicate RUNX1 in aberrant angiogenesis in multiple conditions,” the authors write.
Several authors have filed a provisional patent application on RUNX1 regulation for the treatment of aberrant angiogenesis and proliferative diabetic retinopathy.