Table 5 Future directions for eye-to-brain connectivity (SDG5)
Research Area | Future Goals |
|---|---|
Combinatorial approaches to multimodal reinnervation of the brain | Implement a combinatorial approach to understand different signaling pathways necessary for neuronal survival, axon regeneration, and guidance to direct eye-brain connectivity |
Distal injury models and in vitro models | Employ these models to simplify experimentation, study regeneration at the single axon level, and investigate the role of neural activity in axon regeneration. Different RGC subtypes may require different guidance cues |
Role of glial cells | Use techniques such as single-cell sequencing, optogenetics, chemogenetics, and transgenic mouse lines to identify specific roles of glial subpopulations in promoting or inhibiting axon regeneration. This may include physiologically ‘normal’ glial subtypes, or one of many reactive glial sub-states |
Overcoming mechanical blockages | Explore the development of strategies that aid donor RGCs in connecting with downstream neurons in the brain, specifically overcoming the mechanical blockage of the lamina cribrosa |
Adult retinal and brain microenvironment | Investigate the spatial–temporal expression/induction of guidance signals in the adult environment and engineer RGCs to respond to specific cues present in the adult retina to promote axon regeneration |
Neural Activity | Investigate the role of neural activity in axon regeneration among RGC subtypes to develop combinatorial strategies for promoting regeneration broadly |
Retinotopic mapping | Evaluate whether regenerating RGC axons synapsing at subcortical visual centers establish a retinotopic map and develop methods for modulating this process |
Brain regeneration | Develop strategies to regenerate retinorecipient tissue in the brain in optic neuropathies, which may overcome issues with anterograde transsynaptic degeneration in longstanding optic neuropathy |