New therapeutic approach may help treat age-related macular degeneration effectively

Inhibiting a gene involved in the abnormal growth of blood vessels in certain ocular disorders may reduce retinal neovascularization, researchers report in The American Journal of Pathology

Philadelphia, February 22, 2021

Runt-related transcription factor 1 (RUNX1) has been linked to retinal neovascularization and the development of abnormal blood vessels, which result in vision loss in diabetic retinopathy. Now, scientists have found that RUNX1 inhibition presents a new therapeutic approach in the treatment of age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly worldwide. Their results are reported in The American Journal of Pathology, published by Elsevier.

Abnormal growth of blood vessels, or aberrant angiogenesis, arises from the choroid, a part of the eye located behind the retina. This condition, known as choroidal neovascularization (CNV), is present in several ocular diseases that lead to blindness such as AMD. This study is the first to implicate RUNX1 in CNV and to test RUNX1 inhibition therapy for treating CNV. Researchers found that application of a RUNX1 inhibitor, alone or in combination with a standard treatment for AMD, may represent an important therapeutic advance.

“Incomplete response to anti–vascular endothelial growth factor (VEGF) drugs is a critical problem that hinders visual outcomes in CNV. RUNX1 represents a promising therapeutic target that may help address current limitations of anti-VEGF therapy,” explains first author Lucia Gonzalez-Buendia, MD, a retina specialist at Puerta de Hierro-Majadahonda University Hospital (Spain), former postdoctoral fellow at the Schepens Eye Research Institute of Mass Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Researchers induced CNV lesions in mice. Immediately thereafter the mice received a single intravitreal injection of saline, aflibercept (a US Food and Drug Administration–approved treatment for VEGF), the RUNX1 inhibitor Ro5-3335, or a combination of Ro5-3335 and aflibercept. A single intravitreal injection of Ro5-3335 alone significantly decreased the CNV lesion size seven days after induction of the CNV lesions. The combination of Ro5-3335 and aflibercept reduced vascular leakage more effectively than aflibercept alone.

“RUNX1 inhibitors hold significant promise to complement or replace anti-VEGF therapies for patients in which anti-VEGF therapy is no longer effective, and with the potential to be administered topically it could be transformative in the field,” suggests co-lead investigator Joseph F. Arboleda-Velasquez, MD, PhD, Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear, and Assistant Professor of Ophthalmology, Harvard Medical School, Boston, MA, USA.

RUNX1 inhibition combined with anti–vascular endothelial growth factor (anti-VEGF) therapy achieves better control of experimental choroidal neovascularization activity compared to monotherapy (Credit: The American Journal of Pathology). 

RUNX1 was detected in all cell types studied that are known to be involved in CNV pathogenesis, suggesting that RUNX1 inhibition may target not only angiogenesis, but also other processes important in CNV pathogenesis such as inflammation and fibrosis. It has the potential to impact a wide variety of ocular diseases including AMD, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusions, and other angiogenic diseases of the eye.

“Demonstrating the potential of RUNX1 inhibition for the treatment of CNV beyond anti-VEGF therapy presents a unique approach for the treatment of exudative age-related macular degeneration and suggests the importance of future studies to test its efficacy in patients,” concludes co-lead investigator Leo A. Kim, MD, PhD, Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear, and Assistant Professor of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Current treatment for AMD is invasive and loses efficacy over time. Patients are given multiple injections of anti-VEGF drugs into the eye. Around half of all patients report persistent retinal fluid arising from leaky blood vessels despite chronic treatment, which carries a substantial burden for these patients as well as the health system.


Notes for editors
The article is “Treatment of Experimental Choroidal Neovascularization via RUNX1 Inhibition,” by Lucia Gonzalez-Buendia, Santiago Delgado-Tirado, Miranda An, Michael O’Hare, Dhanesh Amarnani, Hannah A.B. Whitmore, Guannan Zhao, Jose M. Ruiz-Moreno, Joseph F. Arboleda-Velasquez, and Leo A. Kim ( It appears online in The American Journal of Pathology, volume 191, issue 3 (March 2021) published by Elsevier.

The article is openly available at

This work was supported by National Eye Institute (NEI)/NIH grants R01EY027739 (L.A.K.) and P30EY003790, the E. Matilda Zieger Foundation for the Blind (L.A.K.), the Karl Kirchgessner Foundation (L.A.K), National Institute of Neurological Disorders and Stroke and National Institute on Aging cofunded grants UH3 NS100121 and RF1 NS110048 (J.F.A.-V.), and the Alfonso Martin Escudero Foundation (S.D.-T.).

Full text of the study is also available upon request; contact Eileen Leahy at +1 732 238 3628 or Journalists wishing to interview the authors should contact Ryan Jaslow, Senior Manager of Public Relations, Mass Eye and Ear, at +1 617 573 4385 or

About The American Journal of Pathology
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.

About Elsevier
As a global leader in information and analytics, Elsevier helps researchers and healthcare professionals advance science and improve health outcomes for the benefit of society. We do this by facilitating insights and critical decision-making for customers across the global research and health ecosystems.

In everything we publish, we uphold the highest standards of quality and integrity. We bring that same rigor to our information analytics solutions for researchers, health professionals, institutions and funders.

Elsevier employs 8,100 people worldwide. We have supported the work of our research and health partners for more than 140 years. Growing from our roots in publishing, we offer knowledge and valuable analytics that help our users make breakthroughs and drive societal progress. Digital solutions such as ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath support strategic research management, R&D performance, clinical decision support, and health education. Researchers and healthcare professionals rely on our 2,500+ digitized journals, including The Lancet and Cell; our 40,000 eBook titles; and our iconic reference works, such as Gray's Anatomy. With the Elsevier Foundation and our external Inclusion & Diversity Advisory Board, we work in partnership with diverse stakeholders to advance inclusion and diversity in science, research and healthcare in developing countries and around the world.

Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers.

Media contacts
Eileen Leahy
+1 732 238 3628

Chhavi Chauhan, PhD, Director of Scientific Outreach
The American Journal of Pathology
+1 240 283 9724