A research team led by Botondo Roska from the Institute of Molecular Ophthalmology Basel (IOB), together with colleagues, has discovered a genetic pathway and a compound that helps protect cone photoreceptors. These cells are damaged in diseases such as age-related macular degeneration, which is a major cause of vision loss.
Cone photoreceptors are concentrated in the macula and are essential for reading, recognizing faces, and recognizing colors. When these cells die, central vision is lost, as in many inherited retinal diseases and macular degeneration. Despite decades of scientific effort, no approved treatments can stop this process. This study, led by first authors Stefan Spirig, Alvaro Herrero Navarro, and colleagues, aims to address this gap using a human-based experimental system.
Large-scale screening of compounds in human retinal models
To explore potential treatments, researchers tested more than 2,700 compounds across 20,000 human retinal organoids. The results revealed both promising leads and important safety concerns.
- Some classes of compounds damage cone cells, highlighting potential risks
- Several molecules have been discovered that protect cone photoreceptors from degeneration
- Blocking casein kinase 1 emerges as an important defense strategy
The scientists selectively labeled cone photoreceptors so they could track how these cells responded over time under controlled stress conditions that mimic disease. This setup allowed us to systematically evaluate compounds with known molecular targets.
Check the key protection mechanism
Analysis revealed a consistent pattern. The two kinase inhibitors repeatedly showed strong protective effects and aided the long-term survival of pyramidal cells. These benefits were observed across a variety of stress conditions and were also confirmed in mouse models of retinal degeneration, suggesting that the findings may have broader applicability.
In addition to identifying protective pathways, the research team published a detailed dataset covering all compounds tested, their molecular targets, and their effects on cone survival in human tissues. This resource is expected to support the development of treatments aimed at preserving central vision and help researchers more systematically assess potential retinal toxicity.
Getting closer to preventing vision loss
By combining retinal biology, organoid technology, and large-scale compound screening, this study provides a strong foundation for future treatments. This advances a long-standing goal in ophthalmology to protect the cells that enable vision.
