Spatially Resolved Transcriptomics Reveal Changing Landscape of Survival Molecular Signatures in Age-related Macular Degeneration

We study AMD because it accumulates debris beneath the retinal pigment epithelium (RPE), forming so-called “Drusen” analogous to senile plaques of Alzheimer's, including the accumulation of amyloid-beta peptide. We found a decrease in components of the pathway leading to the formation of the pro-homeostatic mediators, the elovanoids (ELVs), specifically in the rod photoreceptors of retinas from donors with age-related macular degeneration (AMD). Retinas were formalin-fixed paraffin-embedded (FFPE), and 5µm microtome sectioning, H&E staining, 10X Genomics Visium CytAssist, and Illumina Sequencing were followed by analysis with Spaceranger and Seurat bioinformatics. By mapping the transcriptome of the human retina, we found gene expression differences in the normal retinas compared to the AMD retinas, both in the rod and cone areas. Transferrin (TF), APOE, and ABCA4 genes were decreased in AMD. Our data have uncovered gene clusters and transcriptomic signatures in regulatory pathways of cell survival in rods and cones in AMD.