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A preclinical study from Mass Eye and Ear offers hope for patients at risk of blindness caused by proliferative vitreoretinopathy (PVR), a severe complication of retinal detachment or eye trauma. PVR occurs when scar tissue forms inside the eye, detaching the retina and impairing vision. The novel therapy, described in Science Translational Medicine, uses mRNA technology to inhibit the key protein RUNX1, which drives the formation of scar tissue and abnormal blood vessels. This therapy could become a game-changer for retinal diseases, especially as current treatment options are limited to surgery, which often exacerbates the condition.
mRNA as an Eye Therapy: A First in Ophthalmology
This study marks a significant milestone as the first to deliver mRNA-based treatments directly into the eye without causing excessive inflammation. Researchers developed an mRNA molecule, RUNX1-Trap, designed to block the RUNX1 protein from activating genes that transform eye cells into scar tissue. In lab and preclinical models, RUNX1-Trap prevented the growth of scar tissue and abnormal blood vessels in patient-derived cells, animal models, and tissue samples.
Co-corresponding author Dr. Leo A. Kim emphasized the importance of these findings: “We hope that these early findings can usher in new treatment options for PVR and other eye diseases.”
While mRNA therapies are typically used to increase protein expression, the unique approach in this study used a dominant-negative inhibitor strategy to trap and suppress RUNX1. This innovative application of mRNA demonstrates its potential for treating complex conditions beyond its current uses.
New Pathways for Treating Eye Diseases
PVR is a serious, sight-threatening condition with no approved pharmacological treatments. By targeting RUNX1, a protein implicated in both fibrosis and abnormal angiogenesis, this therapy may address the root cause of scar formation and vessel growth, rather than merely managing symptoms.
The researchers believe the findings could extend to other retinal diseases, such as wet age-related macular degeneration and diabetic retinopathy, which also involve overactive RUNX1. However, challenges remain. The transient nature of mRNA in cells raises questions about the longevity of its effects, and patients might require multiple doses to maintain efficacy.
Study co-first author William P. Miller, Ph.D., underscored the broader implications of the work, stating, “It demonstrates novel applications of mRNA technology in ophthalmology and has implications for other aspects of medicine as well.”
As research continues, efforts will focus on optimizing the timing of therapy, prolonging mRNA’s half-life, and exploring its use for other conditions. This study serves as an encouraging proof of concept for mRNA therapies in ophthalmology, holding promise for a future where vision loss from PVR and similar diseases can be prevented.