Light-Responsive MicroRNAs in Human Retinal Tissue are Differentially Regulated by Distinct Wavelengths of Light

Retinal microRNA (miRNA) molecules play critical roles in a wide range of processes including cell proliferation, cell death, and synaptic plasticity. Recently they have been shown to regulate crucial processes that are associated with perception of light including visual function, light adaptation, and control of genes regulating circadian light entrainment. Despite extensive work on retinal miRNAs in different model organisms, light-regulated miRNAs in human retina are not known. 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 in-house-developed photostimulation device, we found that 51 miRNAs are up- or downregulated upon brief photostimulation periods. Clustering analysis revealed that only two miRNA families and three clusters are upregulated, while eight families and ten cluster are downregulated upon photostimulation. Additionally, we found that the light-regulated miRNAs have rapid turnover, and their expression is differentially regulated by distinct wavelengths of light. This study demonstrates that only a small subset of miRNAs is light-responsive in human retinal tissue and the generated human retinal organoids are a valuable model for studying the molecular mechanisms of light perception in the retina.