Abundant Neural circRNA Cdr1as Is Not Indispensable for Retina Maintenance

Chen XJ, Li ML, Wang YH, Mou H, Wu Z, Bao S, Xu ZH, Zhang H, Wang XY, Zhang CJ, Xue X, Jin ZB.

Frontiers in Cell and Developmental Biology · 6 Nov 2020 · doi: 10.3389/fcell.2020.565543

Chen et al 2020

The role of circular RNAs is not well understood, including Cdr1as, which is abundant in vertebrate retina. Chen et al show that CDR1as-KO mice had only minor deficits. Those included reduced contrast sensitivity, as measured with our OptoDrum. Overall, however, Cdr1as abundance is not required for retinal development and maintenance.

Abstract

Cdr1as is the abundant circular RNA (circRNA) in human and vertebrate retinas. However, the role of Cdr1as in the retina remains unknown. In this study, we aimed to generate a Cdr1as knockout (KO) mouse model and investigate the retinal consequences of Cdr1as loss of function. Through in situ hybridization (ISH), we demonstrated that Cdr1as is mainly expressed in the inner retina. Using CRISPR/Cas9 targeting Cdr1as, we successfully generated KO mice. We carried out ocular examinations in the KO mice until postnatal day 500. Compared with the age-matched wild-type (WT) siblings, the KO mice displayed increased b-wave amplitude of photopic electrophysiological response and reduced vision contrast sensitivity. Through small RNA profiling of the retinas, we determined that miR-7 was downregulated, while its target genes were upregulated. Taken together, our results demonstrated for the first time that Cdr1as ablation led to a mild retinal consequence in mice, indicating that Cdr1as abundance is not indispensable for retinal development and maintenance.