Retinal organoid study identifies pathways and compounds to protect cone cells

Scientists led by Botond Roska at the Institute of Molecular and Clinical Ophthalmology Basel (IOB) and collaborators have identified genetic pathways and compounds capable of protecting cone photoreceptors from the degeneration that underlies conditions like age-related macular degeneration.

Cone photoreceptors, concentrated in the macula, are essential for reading, recognizing faces, and perceiving colors. Their death, as it happens in many inherited retinal diseases and macular degeneration, leads to the loss of central vision. Despite decades of research, no approved therapies can halt this process. This new study, conducted by first authors Stefan Spirig, Alvaro Herrero Navarro and collaborators, addresses this unmet need using a human-based experimental system.

Key findings

• More than 2,700 compounds were tested in 20,000 human retinal organoids

• Some compound classes were found to damage cones, highlighting safety risks

• Several molecules were identified that protect cone photoreceptors from degeneration

• Inhibition of casein kinase 1 emerged as a key protective mechanism

Cone photoreceptors were selectively labelled, allowing their fate to be followed over time under controlled stress conditions that mimic disease. This approach enabled a systematic screen of compounds with known molecular targets.

Clear patterns emerged: two kinase inhibitors consistently protected cones over extended periods. The protective effects held across different stress conditions and were further confirmed in a mouse model of retinal degeneration, supporting their broader relevance.

Beyond identifying protective pathways, the study makes a comprehensive dataset publicly available, covering the compounds tested, their molecular targets, and their effects on human cone survival. This resource will guide the development of therapies aimed at preserving central vision and enable a systematic assessment of potential retinal toxicity.

By combining retinal biology, organoid technology, and large-scale compound screening, the work gives researchers a head start in developing new treatments and sharpens focus on a long-standing goal in ophthalmology: protecting the very cells that make sight possible.