The Fas Receptor: A Key to Preserving Vision in Genetic Eye Disease

Inherited retinal degenerations (IRD) are a group of eye diseases that lead to progressive vision loss. The challenge in treating them is that they can be caused by mutations in over 300 different genes, making it nearly impossible to develop a unique therapy for each one. This creates a significant unmet need for a "mutation-independent" approach—a single therapy that could work for many different forms of the disease.

Our research, "Preservation of retinal structure and function in two mouse models of inherited retinal degeneration by ONL1204, an inhibitor of the Fas receptor", explores one such promising approach. Our work focuses on a key protein called the Fas receptor, which is a major driver of cell death and inflammation in the retina. Previous research had already shown that Fas contributes to retinal degeneration in a variety of other eye diseases, and that blocking it can protect the retina.

In this study, we tested a small molecule called ONL1204, which inhibits the Fas receptor, on two different mouse models of inherited retinal degeneration. The two mouse models mimic two different genetic forms of the human disease. The results were very promising: in both models, treatment with ONL1204 led to a decrease in cell death and inflammation. This translated to enhanced photoreceptor survival and improved visual function, which we measured by assessing the thickness of the retina and its electrical responses to light.

These findings suggest that targeting the Fas receptor could be a powerful, mutation-independent strategy for preserving the retina and vision in patients with inherited retinal degenerations, regardless of the specific genetic cause.

For more information, please see the full publication here.