Beyond canonical pathways: early retinal transcriptomic response to light-induced degeneration in the zebrafish larva
The zebrafish (Danio rerio) is widely used to investigate the cellular and molecular mechanisms that support retinal regeneration. Although several adult injury paradigms have been established, models that capture the earliest stages of degeneration and Müller glia-mediated repair in larvae remain comparatively underexplored. Here, we validate a light-induced retinal degeneration (LIRD) paradigm at the larval stage as a tractable system to study acute phototoxic injury and early regenerative responses. This approach enables high-throughput RNA sequencing and provides a comprehensive transcriptomic view of retinal responses 48 hours after injury. At this timepoint, larvae display photoreceptor loss and robust Müller glia activation and proliferation, mirroring key features described in adult LIRD models. Transcriptomic analyses further highlight both canonical and previously undercharacterised pathways engaged during the early injury response. Together, this work establishes larval LIRD as a practical and informative model and provides a resource for hypothesis-driven studies aimed at dissecting the molecular events that initiate retinal regeneration. Overall design: Two experimental groups were analyzed: control and light damage (LIRD) (n = 10–11 animals per group). Retinal RNA-seq was performed on Danio rerio (paired-end 150 bp, Illumina NovaSeq 6000). Differential expression and pathway analyses were conducted to assess the impact of LIRD.