Abstract
Purpose :
The fovea, a tiny central region of the retina, enables high-acuity vision for primates. It is only present in anthropoids among mammals. The evolutionary and developmental processes that led to the formation of the fovea have remained unclear. To understand the cellular and molecular mechanisms driving foveal specialization, we studied the postnatal development of the fovea in the marmoset—a primate with ancient evolutionary ties.
Methods :
We used single-cell RNA sequencing (scRNA-seq) to profile marmoset foveal and peripheral retina cells at neonatal and adult stages. The scRNA-seq libraries were sequenced using the Illumina HiSeq platform. Reads alignment and cell clustering were performed using Cell Ranger and Seurat. We integrated the foveal cell data from marmosets, macaques, and humans using canonical correlation analysis (CCA). Transcriptomic mapping, signed gene set enrichment analysis (sGSEA), and Earth Mover’s Distance (EMD) score were used for regional and developmental comparisons.
Additionally, we derived key molecular modules for select cell types through GO-PCA analysis and protein-protein interaction networks. SCENIC and single-cell ATAC-seq analysis were used to infer gene regulatory networks, which were further validated using fluorescence in situ hybridization. Finally, NicheNet was used to infer ligand-target gene relationships between crucial cell types.
Results :
Our comparative analysis revealed that marmosets share almost all their foveal cell types with humans and macaques, emphasizing a conserved cellular structure within the primate fovea. Furthermore, we identified distinct maturation paths for each by tracing the developmental trajectory of cell types in the foveal and peripheral retina. In-depth analysis of gene expression differences highlighted that cone photoreceptors and Müller glia, among other, showed the most significant molecular divergence between the two regions. We also uncovered distinct transcriptional regulations that differentiate the foveal and peripheral cones. Finally, predicted ligand-receptor interactions suggested a potential role for Müller glia in supporting the maturation of foveal cones.
Conclusions :
Our findings highlighted a profound cellular conservation of the fovea among marmosets, humans, and macaques and revealed molecular mechanisms underneath fovea specialization.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.