Numb deficiency impairs retinal structure and visual function in mice.

PURPOSE

Numb is expressed in the progenitor and mature neurons throughout the development progress of the retina. We attempted to investigate the role of Numb in the retina and visual system, and the effects of Numb deficiency on retinal structure and visual function.

METHODS

Conditional Numb/Nbl double-knockout mice were generated to observe the retinal damage in Numb deficiency mice. HE staining and immunofluorescence stain were used to observe the structural and molecular changes. The visual function was assessed by electroretinogram (ERG) and optomotor response (OMR). RNA-Seq and RT-PCR were used to detect the differential expression of genes and the related signaling pathways.

RESULTS

Inactivation of Numb/Nbl induces eye apoptosis and retinal neurons impairment observed by HE staining and immunofluorescence stain. The impaired retinal structure and visual function were assessed by ERG and OMR. RNA-seq analysis indicated loss of photoreceptors, synapses and phototransduction related molecules. Immunofluorescence stain of molecular markers recoverin, arrestin, rhodopsin showed disrupted structural integrity of photoreceptors. Additional bipolar cells and synapses related molecular markers indicate synaptic connections were damaged in Numb deficiency mice.

CONCLUSIONS

Inactivation of Numb/Nbl induces eye apoptosis and retinal neurons impairment. Ablation of Numb in retina significantly impaired visual function. The impaired visual function in Numb deficiency mice is related to the damage of photoreceptors, ion/cation channel activity, synapse formation and phototransduction.