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Researchers from Istituto Italiano di Tecnologia, Milan, Italy, have developed a membrane-targeted photoswitch capable of reinstating natural ON and OFF light responses in the degenerate retina. Unlike existing treatments for retinitis pigmentosa (RP), which often indiscriminately activate retinal neurons, Ziapin2 offers a more precise restoration by modulating neuronal capacitance and excitability in a light-dependent manner.
The study demonstrated that, when injected into blind mouse models, Ziapin2 successfully reactivated a variety of retinal ganglion cell (RGCs) responses, restoring distinct light-driven responses that are critical for contrast sensitivity and spatial resolution. The molecule was able to restore both excitatory and inhibitory retinal pathways, mimicking natural visual processing. In vivo tests further showed that treated mice regained optomotor reflexes and exhibited improved light-driven behavior, indicating potential functional vision recovery.
One of the key advantages of Ziapin is its unique mechanism of action. Unlike optogenetic therapies or retinal prostheses, which require genetic modifications or implanted devices, Ziapin2 operates by embedding into cell membranes and altering capacitance based on light exposure. This approach enables selective response restoration without the need for invasive procedures or complex genetic engineering.
Characterized by its innovative photo-transduction mechanism, and with the ability to restore selective activation of RGC subpopulations, Ziapin2 could have “the potential to outperform the existing prosthetic, optogenetic or photo-pharmacological treatments that are currently in clinical testing for RP therapy,” the researchers conclude.
