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Subspecialties Basic & Translational Research, Retina

Early Promise

Scientists from the Oklahoma Medical Research Foundation (OMRF) in Oklahoma City, have been studying the development of blood vessels, including one set that regresses and disappears in murine eyes after birth. The researchers discovered that down-regulation of a specific class of proteins called ETS transcription factors was responsible for this natural blood vessel loss in the eye. A compound called YK-4- 279 acts as an inhibitor of these ETS transcription factors and appeared to be particularly effective in low-flow vessels. The researchers decided to test the effectiveness of YK-4-279 in an oxygen-induced retinopathy mouse model that mimics human disease (including diabetic retinopathy and retinopathy of prematurity) and found: i) YK-4-279 reduced the abnormal neovascular tufts associated with the model and ii) the compound did not appear to affect healthy retinal vessels. Together, these discoveries point to the therapeutic potential of ETS transcription factor inhibitors (1).

Meanwhile, researchers at the University of North Carolina Lineberger Comprehensive Cancer Care Center in Chapel Hill, implanted mice with retinoblastoma tissue to test a new treatment using CAR-T cells (ganglioside GD2-specific lymphocytes – GD2.CAR-Ts) injected into the retina. The result: delayed tumor development. They then combined the CAR-T cells with an immune-boosting interleukin (IL)-15 protein in a water-based gel, which was injected into the retinas of the mice, and found that the majority of treated mice remained tumor-free for up to 70 days. The therapy is currently being used in clinical trials for pediatric neuroblastoma, and the researchers are hoping to see further trials looking at the therapy’s efficacy in retinoblastoma (2).

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  1. CM Schafer et al., Proc Natl Acad Sci USA, [Online ahead of print] (2020). PMID: 33020273.
  2. K Wang et al., Nature Cancer, 1, 990 (2020).
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Aleksandra Jones

Editor of The Ophthalmologist

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