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Stopping Degeneration in its Tracks Part Two

Posted by Ilena Di Toro | Posted on August 17, 2021

GARP2 and GARP1 aren’t the only things that can negatively affect vision. Runt-related transcription factor 1 (RUNX1) can lead to too many blood vessels in the eye, also known as neovascularization. This leads to vision loss in persons with diabetic retinopathy and plays a role in age-related macular degeneration.

Anti–vascular endothelial growth factor (anti-VEGF) drugs have been shown to slow diabetic retinopathy. According to a National Institutes of Health (NIH) funded study, the drugs helps those who were diagnosed with diabetic retinopathy in its early stage, known as non-proliferative diabetic retinopathy. Results from the two-year mark of this study (it is a four-year study) show no effect on vision. That means that the anti-VEGF drugs are no longer effective after a period of time. So, is there anything that can treat conditions like diabetic retinopathy or age-related macular degeneration and preserve vision? Results from a study done in Spain and the U.S. may hold the key.

Scientists at Puerta de Hierro-Majadahonda University Hospital in Spain and the Department of Ophthalmology, Harvard Medical School have found that blocking RUNX-1 may be used as a possible treatment for those with age-related macular degeneration. Researchers wanted to test RUNX1 inhibition as a way to treating choroidal neovascularization, which is present in age-related macular degeneration.

While anti-VEGF drugs are used to treat age-related macular degeneration, they don’t always work. Researchers found that the use of a RUNX-1 inhibitor, either all by itself or in combination with a standard treatment for age-related macular degeneration could be used as treatment.

Scientists induced choroidal neovascularization lesions in mice and immediately afterwards the mice received a single injection of either saline, aflibercept (a treatment for VEGF), the RUNX1 inhibitor Ro5-3335 or a combination of Ro5-3335 and aflibercept. A single dose of Ro5-3335 decreased the lesion size within seven days. The combination of Ro5-3335 and aflibercept reduced leakage in the blood vessels more effectively than aflibercept alone. This shows that the RUNX1 inhibitor Ro5-3335 could be utilized as complement to anti-VEGF treatments or to replace anti-VEGF treatments when they no longer work.

Since RUNX1 was detected in all the cell types in known to be involved in choroidal neovascularization, it can be used as a therapeutic target in order to prevent the development of new blood vessels in the eye, as well as prevent inflammation. It can also be used a target when treating other eye diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity and retinal vein occlusions. Since treatments for age-related macular degeneration aren’t as effective over time, RUNX1 inhibitor Ro5-3335 can be the treatment that those with this condition are looking for.

Once again, research reveals what can be possible treatment avenues for disorders like retinitis pigmentosa and age-related macular degeneration.


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