Challenges in Retinal Circuit Regeneration

Linking Neuronal Connectivity to Circuit Function

抄録

Tremendous progress has been made in retinal regeneration, as exemplified by successful transplantation of retinal pigment epithelia and photoreceptor cells in the adult retina, as well as by generation of retinal tissue from embryonic stem cells and induced pluripotent cells. However, it remains unknown how new photoreceptors integrate within retinal circuits and contribute to vision restoration. There is a large gap in our understanding, at both the cellular and behavioral levels, of the functional roles of new neurons in the adult retina. This gap largely arises from the lack of appropriate methods for analyzing the organization and function of new neurons at the circuit level. To bridge this gap and understand the functional roles of new neurons in living animals, it will be necessary to identify newly formed connections, correlate them with function, manipulate their activity, and assess the behavioral outcome of these manipulations. Recombinant viral vectors are powerful tools not only for controlling gene expression and reprogramming cells, but also for tracing cell fates and neuronal connectivity, monitoring biological functions, and manipulating the physiological state of a specific cell population. These virus-based approaches, combined with electrophysiology and optical imaging, will provide circuit-level insight into neural regeneration and facilitate new strategies for achieving vision restoration in the adult retina. Herein, we discuss challenges and future directions in retinal regeneration research.