From Pigment To Pattern: Mechanisms Shaping Foveal Specialisation

No treatments exist for disorders that arrest foveal development, leaving many children partially sighted or registered blind. This arrest, termed foveal hypoplasia (FH), is most common in pigmentation disorders like albinism. The mechanistic link between melanin synthesis and foveal specialisation remains unclear, preventing therapeutic development. I hypothesise that disrupted L-DOPA/GPR143 signalling and subsequent downstream pathways drive FH pathogenesis. To address this, I have developed zebrafish models that faithfully recapitulate human foveal architecture. This programme will dissect FH mechanisms in vivo using novel FH zebrafish models. Using single-cell RNA sequencing and spatial multi-omics, I will map cell-type-specific transcriptional changes and metabolic gradients within developing foveal tissue, defining the signalling hierarchy governing foveal specialisation. Through targeted pharmacological screening of identified pathway nodes, I will determine critical developmental windows for intervention. Bespoke ultra-high-resolution retinal imaging will enable unprecedented cellular-level phenotyping of human FH patients, directly translating mechanistic insights from models to patients. This integrated programme, combining genetic models, multi-omics approaches, and advanced clinical imaging, will establish the molecular logic underpinning foveal development and identify actionable targets for early-life intervention in children with FH.