Abstract
Purpose :
Runx1 is a transcription factor recently linked to aberrant angiogenesis in proliferative diabetic retinopathy. This study evaluated the role of Runx1 in choroidal neovascularization (CNV) and tested feasibility, safety, and efficacy of a novel drug formulation of a Runx1 inhibitor as a nanoemulsion (eNANO).
Methods :
6-7-week-old C57BL/6J male mice were used for the study. Briefly, for CNV induction, laser photocoagulation was performed with a 532-nm laser attached to Micron III image-guide system using 120 mW of power, 50 ms duration and a 50 mm spot size. Fluorescein angiography was performed 6 days after laser induction. Mice were euthanized 24 hours later, eyes were enucleated and choroidal whole mounts were prepared and stained with Isolectin IB4 and anti-Runx1 antibody. Three study groups (untreated (n=17 eyes), vehicle only (n=17 eyes) and eNANO (n=16 eyes)) were included to assess Runx1 inhibition in CNV formation. For the treated groups, a nanoemulsion containing CBFβ-Runx1 Inhibitor II, Ro5-3335 at 7.92 mM was formulated, and treatment was initiated immediately after laser induction. Topical treatment with vehicle or eNANO was applied 4 times a day during 7 days. In addition, to evaluate safety of the treatment, electroretinography studies were performed to evaluate retinal function after 7 days of treatment in each group (n=24 eyes).
Results :
Runx1 positive cells were observed in CNV lesions 7 days after laser induction. A statistically significant reduction of 30% in CNV area was found in the eNANO treated group compared to vehicle only (*P<0.0180) and untreated (*P<0.0150) groups. (Fig.1) No statistically significant differences were found in scotopic and photopic responses in any of the groups.
Conclusions :
Identification of Runx1 positive cells in whole mounts after laser induction suggests a role for Runx1 in CNV formation. Runx1 inhibition by topical application of nanoemulsion drops appears safe and successful approach to reduce CNV area in mice. This might be used as an alternative or adjuvant therapy to intravitreal injections of anti-VEGF drugs, which is currently the standard of care for antiangiogenic therapy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.