Investigating mechanisms involved in retinal signalling in health and disease through detailed in vivo human electrophysiological investigation (360G-Wellcome-206619_Z_17_Z)

Retinal imaging investigates structure, but not cellular function. Electrophysiology allows direct assessment of the latter. The electroretinogram (retinal electrical response to light) can be recorded non-invasively. As understanding of retinal processing improves, with refinement of mathematic models of current flows, light and dark adaptation, there is scope to probe retinal signalling in great detail. Findings from animal and in vitro studies can be specific to species or laboratory conditions. This project uses in vivo human recording. Novel stimulus protocols will be used in patients with largely monogenic disease (including natural "knock-outs"), and in genetically characterised twins (both using the classic twin study and by exploring further genetic associations including the retinal functional significance of myopia-associated genetic loci). Project goals include the following: 1. A more integrated model of sensory signalling pathways in the retina: elucidating roles of specific proteins (in the photoreceptor-RPE complex and in signal transmission to bipolar cells) 2. Elucidation of a myopia signalling cascade: functional effect of variants that confer susceptibility to myopia These will yield insights into neural processing (with wider implications for neuroscience), retinal disease and myopia. As new gene and stem cell therapies emerge, novel functional assessments can provide objective outcome measures.