Two new compounds may be able to treat retinitis pigmentosa (RP), a group of inherited eye diseases that cause blindness.
The compounds are described in a study in PLOS Biology.1
In RP, the retina protein rhodopsin is often misfolded due to genetic mutations, causing retinal cells to die off, leading to progressive blindness. The study authors said small molecules to correct rhodopsin folding are urgently needed to treat people with the disease. Current experimental treatments include retinoid compounds, such as synthetic vitamin A derivatives, which are sensitive to light and can be toxic, leading to several drawbacks.
In the new study, researchers used virtual screening to search for new drug-like molecules that bind to and stabilise the structure of rhodopsin to improve its folding and movement through the cell.
… treatment with either compound improved the overall retina health and function in these mice by prolonging the survival of their photoreceptors
Two non-retinoid compounds were identified which met these criteria and had the ability to cross the blood-brain and blood-retina barriers. Lab testing showed the compounds improved cell surface expression of rhodopsin in 36 of 123 genetic subtypes of RP, including the most common one. Additionally, they protected against retinal degeneration in mice with RP.
“Importantly, treatment with either compound improved the overall retina health and function in these mice by prolonging the survival of their photoreceptors,” the authors said. They noted that additional studies are needed before the compounds or related compounds can be tested on humans.
Reference
- Ortega JT, Gallagher JM, McKee AG, et al. Discovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa. 2025; PLoS Biol 23(1): e3002932. Available at: journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002932.
