Researchers at the Moscow Institute of Physics and Technology (MIPT) and the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences have for the first time used the patch‑clamp technique to analyse three-dimensional retinal organoids – miniature lab-grown 3D models of human tissue. With this method, they created an electrical passport of photoreceptors, the cells that convert light signals into images.
Patch-clamp is an electrophysiological method that measures ion currents across the cell membrane in real time. Photoreceptors possess ion channels that pass sodium, potassium, calcium and other charged particles. The technique can check whether these channels are working and how actively, as well as study how the cell interacts with its environment.
Previously, researchers had no way to precisely verify how well lab-grown photoreceptors matched native ones in functional characteristics. Organoids could fail to generate an electrical response or work erratically. Using patch-clamp made it possible to measure ion movement through the cellular channels. The data obtained matched the parameters of photoreceptors from adult primates, confirming the model’s validity.
The Russian researchers’ development opens new possibilities for the pharmaceutical and medical industries. Drugs for degenerative retinal diseases can now be tested on an accurate replica of living tissue, improving the predictability of preclinical studies. An objective criterion for monitoring organoid maturation has emerged: by day 150 of cultivation, the cells electrically match the adult phenotype. Moreover, bionic implants will be able to generate stimulation based on real electrical properties of photoreceptors, making the stimulation gentler and more effective.
In the future, the scientists plan to record the interaction between photoreceptors and bipolar cells – the next link in the visual pathway – and to combine patch-clamp with optogenetics, a technology that controls cells with light. This will enable more accurate models for testing ophthalmic drugs and developing next-generation implants.
Earlier, Russian and international molecular biologists proposed a new method for studying semispiral receptors – proteins that relay signals within cells. The approach, called thermal shift analysis (TSA), makes it possible to analyse the interaction of these receptors with biologically active molecules more simply and cheaply than traditional technologies.