Anp32b Deficiency Suppresses Ocular Development by Repression of Pax6

This study aimed to elucidate the role and molecular mechanisms of acidic leucine-rich nuclear phosphoprotein 32 kDa B (Anp32b) deficiency in ocular development.

We used constitutive C57BL/6-derived Anp32b-/- mice to elucidate the role of Anp32b in ocular development, including the phenotype and proportion of eye malformation in different genotypes. RNA-seq analysis and rescue experiments were performed to investigate the underlying mechanisms of Anp32b.

Deletion of Anp32b contributes to severe defects in ocular development, including anophthalmia and microphthalmia. Moreover, Anp32b is highly expressed in the lens, and Anp32b-/- embryos with microphthalmia often exhibit severely impaired lens development. Mechanistically, ANP32B directly interacts with paired box protein 6 (PAX6), a master transcriptional regulator, and enhances its transcriptional activity. Overexpression of PAX6 partially but significantly reverses the inhibition of proliferation observed in ANP32B knockdown lens epithelial cells.

Our findings indicate that Anp32b deficiency suppresses ocular development by repressing Pax6 and identify that Anp32b is a viable therapeutic target for ocular developmental defects.