Researchers identify new target for abnormal blood vessel growth in the eyes

April 11, 2017

Regulating transcription factor RUNX1 using small molecule drugs a promising novel therapy for diseases of the retina, including advanced diabetic eye disease.

Boston, Mass.— A team led by Massachusetts Eye and Ear researchers has identified a novel therapeutic target for retinal neovascularization, or abnormal blood vessel growth in the retina, a hallmark of advanced diabetic eye disease (proliferative diabetic retinopathy). According to a report published online today in Diabetes, the transcription factor RUNX1 was found in abnormal retinal blood vessels, and by inhibiting RUNX1 with a small molecule drug, the researchers achieved a 50 percent reduction of retinopathy in preclinical models. These findings pave the way for new therapies that address diabetic retinopathy and other conditions involving abnormal vessel growth within the retina.

“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. Such a treatment could be self-administered by patients and eliminate the need for intravitreal injections,” said co-corresponding author Joseph F. Arboleda-Velasquez, MD, PhD, Assistant Scientist at Schepens Eye Research Institute of Mass. Eye and Ear and Assistant Professor of Ophthalmology at Harvard Medical School.

Neovascularization is a feature of various health conditions, including diabetic retinopathy, wet age-related macular degeneration (AMD), retinopathy of prematurity and cancer. In the case of diabetic retinopathy — the most common diabetic eye disease and a leading cause of blindness in American adults — blood vessels in the retina (the structure in the back of the eye that senses and perceives light) become damaged and leak fluid. Accumulation of fluid into the retina can lead to swelling at the center of the retina (macular edema) and growth of pathological blood vessels on its surface. As diabetes-related damage progresses, these vessels can leak, rupture, or cause retinal detachment leading to impaired vision.

In the Diabetes report, the authors studied tissue from patients with proliferative diabetic retinopathy. They identified the presence of RUNX1 in the diseased blood vessels but not in the normal blood vessels. Next, they used a small molecule drug originally developed as a cancer therapy to inhibit the activity of RUNX1 in the eye, which led to a significant reduction of abnormal blood vessels.

Current strategies for treating abnormal blood vessel growth in the retina for proliferative diabetic retinopathy include laser treatments or eye injections targeting a growth factor (VEGF). While these therapies have been remarkably successful in saving vision in many patients they can, in rare instances, trigger complications such as retinal hemorrhages, detachments or retinal atrophy.

The study authors are hopeful that inhibiting RUNX1 may present a more targeted opportunity for managing the retinopathy of certain eye conditions — perhaps earlier in the disease process, before the abnormal blood vessels develop. Future studies will test whether the drug can be delivered through topical eye drops rather than by injection, and further explore the relationship between RUNX1 and VEGF, as these factors seemingly both 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, a retina surgeon at Mass. Eye and Ear and 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.”

In addition to Drs. Kim and Arboleda-Velasquez, authors on the Diabetes report include co-corresponding author, and first authors Jonathan D. Lam, MD, and Daniel J. Oh M.D., of Schepens Eye Research Institute of Mass. Eye and Ear. Additional co-authors include Lindsay L. Wong, Dhanesh Amarnani, Cindy Park-Windhol, PhD, Angie V. Sanchez MD, and Jonathan Cardona-Velez MD, also of Schepens Eye Research Institute of Mass. Eye and Ear, Declan McGuone, MD, and Anat O. Stemmer-Rachimov, MD, of the Kubik Laboratory for Neuropathology of Mass General,, and, of the Retina Service of Mass. Eye and Ear, Diane R. Bielenberg, PhD, of Boston Children’s Hospital, and Xiaowu Gai, PhD, and Lishuang Shen, PhD of Children’s Hospital Los Angeles.

Support for the study includes National Institutes of Health grants R01EY005318, R00EY021624, UH2NS100121-01, R21EY027061, K12EY16335 and P30EY003790. Additional support was provided by the American Diabetes Association Innovation Award, the Massachusetts Lions Eye Research Fund, the E. Matilda Ziegler Foundation for the Blind, the Karl Kirchgessner Foundation, the Harvard Medical School Department of Ophthalmology and the Howard Hughes Medical Institute Medical Research Fellows Program.

About Massachusetts Eye and Ear 
Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. In the 2016–2017 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #1 in the nation for ear, nose and throat care and #1 in New England for eye care. For more information about life-changing care and research, or to learn how you can help, please visit

About the Harvard Medical School Department of Ophthalmology
The Harvard Medical School (HMS) Department of Ophthalmology ( is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.

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