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bioRxiv · 10.1101/2025.07.30.635135

Dicer is essential for proper maturation, composition, and function in the postnatal retina.

Kang, S.·Larbi, D.·Bruns, E.·Hahne, K.·Khodadadi-Jamayran, A.·Sreenivasaiah, C.·Carneiro, M. L.·Andrade, M.·Batsuuri, K.·Chen, S.·Jager, J.·Viswanathan, S.·Clark, B. S.·Wohl, S. G.
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Abstract

microRNAs (miRNAs) play a pivotal role during the early phases of retinal development, but their impact on late-phase retinogenesis is unknown. We depleted miRNAs in late retinal progenitor/precursor cells (RPCs/PCs) via a conditional Dicer knock-out. Optical coherence tomography (OCT), electroretinography (ERG), histological, and transcriptional analyses were conducted in young and adult mice. Alterations in gene expression of late-born cells were observed as early as postnatal day 7 (P7), resulting in impaired rod function, a significantly reduced number of rod bipolar cells and their associated function, and a decreased Muller glia population at adult age. These defects appear to be caused by a delay in differentiation/ incomplete maturation, as indicated by an enlarged progenitor/precursor population at young ages that persists into adulthood. Notably, an increased population of HuC/D+ amacrine cells was found. Luciferase assays led us to speculate that this increase may be due to the absence of Elavl3 suppression via RPC-miRNAs. This suggests that Dicer/miRNAs in late RPC/PCs are essential for the proper formation and maturation of late RPC progenies and may also play a role in regulating cell state. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/635135v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@9e0950org.highwire.dtl.DTLVardef@1757e2corg.highwire.dtl.DTLVardef@aeb5ecorg.highwire.dtl.DTLVardef@29accb_HPS_FORMAT_FIGEXP M_FIG C_FIG Summary statementLate-retinal progenitor microRNAs are essential for proper postnatal retinogenesis and retinal function.

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Kang, S., Larbi, D., Bruns, E., Hahne, K., Khodadadi-Jamayran, A., Sreenivasaiah, C., Carneiro, M. L., Andrade, M., Batsuuri, K., Chen, S., Jager, J., Viswanathan, S., Clark, B. S., Wohl, S. G.. 2025-07-31. Dicer is essential for proper maturation, composition, and function in the postnatal retina.. https://doi.org/10.1101/2025.07.30.635135

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