• Massachusetts Eye and Ear, Diabetes

    Scientists from Massachusetts Eye and Ear have identified a new transcription factor involved in retinal neovascularization: Runt-related transcription factor 1 (RUNX1).

    The findings could lead to new therapies for conditions involving abnormal vessel growth within the retina, such as proliferative diabetic retinopathy (PDR).

    In a report published online in Diabetes, the authors showed that RUNX1 was upregulated in vascular endothelial cells obtained from fibrovascular membranes in PDR patients. Next, they used a small molecule drug originally developed as a cancer therapy (Ro5-3335) to inhibit the activity of RUNX1 in the eye, which led to a 50% reduction in abnormal vascularization in a rat model of oxygen-induced retinopathy.

    "Current treatments to control retinal neovascularization require injecting very large proteins, including antibodies, into the eyes of patients, as often as once a month. Our study opens the door for novel modalities of treatment based on small molecules that could cross biological barriers on their own,” said co-corresponding author Joseph F. Arboleda-Velasquez, MD, PhD, assistant scientist at Schepens Eye Research Institute. “Such a treatment could be self-administered by patients and eliminate the need for intravitreal injections.”

    The authors are planning future studies exploring methods for efficient retinal delivery of Ro5-3335 and the relationship between RUNX1 and VEGF, as both factors play a role in angiogenesis.

    "We're hopeful that we may have an opportunity to change the treatment paradigm for these conditions," said co-corresponding author Leo A. Kim, MD, PhD, assistant professor of ophthalmology at Harvard Medical School. "Instead of treating patients after these abnormal blood vessels form in the eye, we may be able to give patients eye drops or systemic medications that prevent their development in the first place.”