From Retina to Brain: Viral Tools for Targeting Retinal Cells and Mapping Visual Circuits.

Abstract

The retina serves as a uniquely accessible entry point to the central nervous system, enabling both cell type-specific manipulation and circuit-level interrogation of visual pathways. Viral vectors have emerged as indispensable tools in this context, facilitating precise gene delivery, functional perturbation, and connectivity mapping across retinal and brain circuits. Among retinal neurons, retinal ganglion cells (RGCs) represent a major focus due to their role as the sole output neurons conveying visual information to central targets. Accordingly, recent advances in viral engineering including capsid design, transcriptional targeting, and synthetic regulatory elements have significantly improved the efficiency and specificity of RGC-directed gene delivery, while also enabling targeting of diverse retinal cell populations. Beyond retinal targeting, viral tools have transformed the study of RGC connectivity with downstream brain nuclei. In particular, transsynaptic and projection-specific viral strategies now enable mapping of RGC inputs and outputs across visual pathways with increasing precision. Approaches using retrograde AAVs, monosynaptic rabies systems, and anterograde tracers have revealed complex, cell type-dependent wiring patterns linking the retina to thalamic, midbrain, and cortical circuits. In this review, we highlight current viral technologies for targeting RGCs and other retinal cell types and subsequently discuss viral approaches for dissecting retinal-brain connectivity. Together, these complementary strategies provide a powerful framework for linking molecular identity, circuit architecture, and visual function, thereby advancing both basic neuroscience and translational efforts in vision research.