Cells in the human retina must rapidly adapt to constantly changing visual stimuli. This fast adaptation to varying levels and wavelengths of light helps to regulate circadian rhythms and allows for adaptation to high levels of illumination, thereby enabling the rest of the visual system to remain responsive. It has been shown that retinal microRNA (miRNA) molecules play a key role in regulating these processes. However, despite extensive research using various model organisms, light-regulated miRNAs in human retinal cells remain unknown. Here, we aim to characterize these miRNAs. We generated light-responsive human retinal organoids that express miRNA families and clusters typically found in the retina. Using an in-house developed photostimulation device, we identified a subset of light-regulated miRNAs. Importantly, we found that these miRNAs are differentially regulated by distinct wavelengths of light and have a rapid turnover, highlighting the dynamic and adaptive nature of the human retina.

Biosciences Institute Faculty of Medical Sciences Newcastle University Newcastle upon Tyne NE2 4HH UK

Biosciences Institute Newcastle University Newcastle upon Tyne NE1 7RU UK

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Pathology and Laboratory Medicine Division of Neuropathology Philadelphia PA USA

Institute of Animal Physiology and Genetics The Czech Academy of Sciences Brno Czech Republic

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