Redox Regulation of Retinal Ageing: Mechanisms and Cross-Species Insights from Killifish to Mammals

Objective

Age-related decline in retinal function is a major contributor to vision loss, yet the molecular mechanisms linking redox imbalance to neuronal and glial dysfunction remain poorly understood. This project will investigate redox-regulated pathways of retinal ageing using the African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate that provides unique opportunities for accelerated ageing research. Through single-cell transcriptomics, I will map age-associated redox gene networks in killifish Müller glia and compare them with datasets from mouse and human retina to establish conserved signatures of ageing. At the protein level, I will identify post-translational modifications of candidate redox regulators and test their functional impact using transgenic killifish lines. Functional consequences of redox modulation will be assessed through electrophysiological recordings, behavioural assays, and histological markers of degeneration. This fellowship will deliver a cross-species framework for understanding how redox dynamics govern retinal ageing, identifying core molecular pathways that sustain glial homeostasis and neuronal integrity. Training at University College London under the supervision of Prof. Ryan MacDonald will provide advanced expertise in fish genetics, single-cell biology, and neurophysiology, establishing me as an independent researcher in redox biology and ageing. The project will generate broadly relevant insights with potential to guide future therapeutic strategies against retinal neurodegeneration.