Figure 5.

Molecular characteristics of aging primate retina and aging-related changes in cell-cell communication. (a) Co-expression patterns of up-regulated genes among aging stages. (b) Enriched gene ontology terms of up-regulated genes. (c) Heatmap illustrating log2 fold changes of up-regulated genes to cell types at different aging stages in human adult retina. (d) Co-expression patterns of down-regulated genes among aging stages. (e) Enriched gene ontology terms of down-regulated genes. (f) Neuronal or non-neuronal cell proportions of human and macaque adult retina at different aging stages. (g, h) Immunostaining of RCVRN/RHO (g) in human retina of Y52 and Y87, IBA1 (h) of Y54 and Y87. Scale bars: 20 μm (g), 25 μm (h, top) and 5 μm (h, bottom). Experiments were repeated three times independently with similar results. (i) Proportion of rod subclasses (MYO9A⁺ and MYO9A⁻) in human adult retina at each stage. (j) In situ RNA hybridization of MYO9A in Y35 and Y86 human retina. Blue, DAPI (nucleus marker). Scale bars: 10 μm (left) and 5 μm (right). Experiments were repeated three times independently with similar results. (k) Immunostaining of OTX2 in human Y54, Y77 and Y87 peripheral retina. Solid arrowheads indicate positive cells; empty arrowheads indicate negative cells. Scale bars: 25 μm (left) and 5 μm (right). Experiments were repeated three times independently with similar results. (l) Quantification of OTX2⁺ cells in outer nuclear layer (ONL) at various ages, related to Fig. 5k. Data are means ± s.e.m. Each sample was counted from three different slices. (m) Aging-related ligands produced and secreted by MGs with receptors expressed in rods (left) and aging-related ligands produced and secreted by BCs with receptors expressed in rods (right). In all panels, nodes represent ligands or receptors expressed in denoted cell type, and edges represent protein-protein interactions between them. Node color represents magnitude of DEG. Edge color represents sum of scaled differential expression magnitudes from each contributing node, whereas width and transparency are determined by magnitude of scaled differential expression. These figures have been filtered such that top 100 edges representing most differentially expressed node pairs are shown. (n) Dot plot for VEGF-A expression in different cell types at each stage in human adult retina. Size of each dot represents percentage of cells in each cluster. Gray to red indicates gradient from low to high gene expression. Experiments were repeated three times independently with similar results. (o) Confocal imaging of LAMININ in human Y35, Y52, Y86 and Y87 peripheral retina. Scale bar: 50 μm. Experiments were repeated three times independently with similar results.