Aging induces cell loss and a decline in phagosome processing in the mouse retinal pigment epithelium.

ABSTRACT

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and dysfunction in the retinal pigment epithelium (RPE) with age is known to contribute to disease development. The aim of this study was to investigate how the C57BL/6J mouse RPE changes with age. RPE structure was found to change with age and eccentricity, with cell size increasing, nuclei lost, and tight junctions altered in the peripheral retina. Phagocytosis of photoreceptor outer segments (POS) by the RPE was investigated using gene expression analysis and histology. RNA-Seq transcriptomic gene profiling of the RPE showed a downregulation of genes involved in phagosome processing and histological analysis showed a decline in phagosome-lysosome association in the aged tissue. In addition, failures in the autophagy pathway that modulates intracellular waste degradation were observed in the aged RPE tissue. These findings highlight that RPE cell loss and slowing of POS processing contribute to RPE dysfunction with age and may predispose the aging eye to AMD development.