miRNA 183 Knockout Alters Cone Subtype Distribution, Transcriptional Activity and ERG Signals in the Tetrachromatic...

miRNA 183 is part of the miRNA-183/96/182 cluster, which is known to play a decisive role in fine-tuning the activity of gene expression in sensory systems, particularly in the retina. Although miR-183 is essential for retinal gene expression in mammals, the contributions of miR-183 to mRNA expression and photoreceptor development and function in other classes of animals have not been fully elucidated. Danio rerio have a diverse photoreceptor system, with cone photoreceptors sensitive to red, green, blue and ultraviolet (UV) light. We generated knockout zebrafish by deleting the whole seed sequence of miR-183. RNAscope results show no expression of mature miR-183 and decreased expression of miR-182 in both dorsal and ventral KO retinas. The number of UV and blue photoreceptors decreased, and the photoreceptors showed shortening or loss of their outer segments. In the absence of miR-183, the transcription levels of phototransduction genes were altered differentially at 3 and 12 months of age. Finally, photoreceptor-only electroretinogram (PIII) signals showed attenuated amplitudes of red and green-sensitive photoreceptor subtypes while the b-wave amplitudes reflecting second order retinal neuron activity, were decreased in response to the UV-, blue-, and red-stimulating wavelengths. These results reveal a novel microRNA regulatory network in teleost fish and indicate that miR-183 plays a facilitative role in retinal development and function, especially for short-wavelength-sensitive photoreceptor subtypes.