Purpose: Physiologic neuronal apoptosis, which facilitates the developmental maturation of the nervous system, is regulated by neuronal activity and gene expression. Circular RNA (circRNA), a class of non-coding RNA, regulates RNA and protein expression. As the relationship between circRNA and apoptosis is unknown, we explored changes in expression patterns of circRNA during physiologic neuronal apoptosis.
Methods: High-throughput sequencing was used to explore changes in the expression of circRNA in the postnatal developing rat retina. Neuronal apoptosis was determined with immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the rat retinal ganglion cell layer.
Results: In total, 2,654, 7,201, and 5,628 circRNA species were detected in the postnatal day (P)3, P7, and P12 rat retina, respectively. Of these circRNA species, 1,371 changed statistically significantly between P3 and P7 and 1,112 changed statistically significantly between P7 and P12. Normal developmental apoptosis, measured with the ratio of apoptotic (caspase-3- or TUNEL-positive) cells to normal cells, showed an increase from P3 to P7 and then a reduction from P7 to P12. In addition, 15 circRNAs whose host genes were associated with apoptosis were differentially expressed during the early development period.
Conclusions: These results associate circRNAs with neuronal apoptosis, providing potential mechanisms and treatment targets for physiologic and drug-induced apoptosis in the developing nervous system.