Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration

PURPOSE. Age is the main risk factor for age-related macular degeneration (AMD), a leading cause of blindness in the elderly, with limited therapeutic options.METHODS. Here, we analyze the transcriptomic characteristics and cellular landscape of the aging retinas from controls and patients with AMD.RESULTS. We identify the aging genes in the neural retina, which are associated with innate immune response and inflammation. Deconvolution analysis reveals that the estimated proportions of M2 macrophages are significantly increased with both age and AMD severity. Moreover, we find that proportions of Muller glia are significantly increased only with age but not with AMD severity. Several genes associated with both age and AMD severity, particularly C1s and MR1, are strong positively correlated with the proportions of Muller glia.CONCLUSIONS. Our studies expand the genetic and cellular landscape of AMD and provide avenues for further studies on the relationship between age and AMD.

Automated summary

In this study, the transcriptomic characteristics and cellular landscape of aging retinas in control individuals and AMD patients were analyzed. Aging genes associated with innate immune response and inflammation in the neural retina were identified. Deconvolution analysis revealed an increased proportion of M2 macrophages with both age and AMD severity, while the proportion of Muller glia only increased with age. Several genes, particularly C1s and MR1, were strongly correlated with the proportion of Muller glia and with age and AMD severity.