Optogenetic approaches for neural tissue regeneration: A review of basic optogenetic principles and target cells for therapy

Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins. This review article discusses the fundamental principles of optogenetics, including the activation of both excitatory and inhibitory opsins, as well as the development of optogenetic models that utilize recombinant viral vectors. A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges. These strategies include the use of adeno-associated viruses, cell-specific promoters, modified opsins, and methodologies such as bioluminescent optogenetics. The application of viral recombinant vectors, particularly adeno-associated viruses, is emerging as a promising avenue for clinical use in delivering opsins to target cells. This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery. The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes. The article also examines different cellular targets for optogenetics, including neurons, astrocytes, microglia, and Schwann cells. Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation. Research has demonstrated that optogenetic stimulation of both neurons and glial cells - particularly the distinct phenotypes of microglia, astrocytes, and Schwann cells - can have therapeutic effects in neurological diseases. Glial cells are increasingly recognized as important targets for the treatment of these disorders. Furthermore, the article emphasizes the emerging field of bioluminescent optogenetics, which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time. By integrating molecular genetics techniques with bioluminescence, researchers have developed methods to monitor neuronal activity efficiently and less invasively, enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods. Evidence has shown that optogenetic modulation can enhance motor axon regeneration, achieve complete sensory reinnervation, and accelerate the recovery of neuromuscular function. This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization. Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system. They enable precise control of neural circuits and may offer new treatments for neurological disorders, particularly spinal cord injuries, peripheral nerve injuries, and other neurodegenerative diseases. © 2025 Elsevier B.V., All rights reserved.