Abstract
Purpose :
During embryogenesis, a transitory hyaloid vasculature (HV) of the vitreous provides temporary nutrients for the fetal ocular tissues. Failure in HV regression leads to persistent fetal vasculature (PFV), a pathological condition accounting for 4.8% of children's blindness in the USA, yet the mechanisms remain to be fully understood. Fz5 mutant mice manifesting non-cell autonomous PFV, thus, may serve as a generic model for understanding PFV.
Methods :
In this study, we performed single-cell RNA sequencing (sc-RNAseq) of the vitreous cells derived from normal and Fz5 mutant mice at two timepoints, postnatal day 3 (P3) and P6, representing starting and ongoing stages of HV regression.
Results :
Ten major cell types were found in both normal and Fz5 mutant vitreous at P3, with similar proportions. Despite more cells in the mutant vitreous at P3, most of them declined sharply at P6 to similar levels of the wild type. Further characterization of the remaining P6 clusters revealed several molecular features coincided with their respective number distributions to genotypes. Remarkably, cluster 20 (C20) expressed the highest neural crest (NC) features with the richest ligand-receptor (L-R) pairs among melanocyte clusters, whereas the endothelial C1 and macrophage C5 showed the opposite. Furthermore, vitreous samples from two PFV patients have overlapping cell types and molecular features with the mice.
Conclusions :
The present study documented molecular features of the regressing HV, suggesting that excess vitreous migration of the periocular neural crests is a common feature of PFV pathogenesis.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.