Fig 2

A schematic diagram of consequences of the senescent retina and induction of SASP during progression of AMD. A healthy retina is an immune-privileged ocular tissue, with active immune regulatory networks and immune cell networks supporting normal retinal cell morphology and function [1, 7]. In contrast, a “senescent” retina has both damaged cells and impaired function with alterations in microglial morphology, migration, and infiltration of systemic immune cells. Additionally, resident neuronal cells (ganglion cells, horizontal cells, amacrine cells, and photoreceptors), RPEs, and microglia/macrophages, enter a senescent state in the senescent retina. Drusen begin to accumulate between the Bruch’s membrane and RPE or in the subretinal space (subretinal drusenoid deposits). The Bruch’s membrane thickens and choriocapillaris has a reduced vascular network alongside thinning and diminishing vessels in the aging choroid. Numerous SASP factors, such as IL-6, IL-12, TNF-α, IFN-γ, and IL-8, are released from the senescent retinal cells. ROS, in tandem with damaged DNA, further promote the age-related decline in RPE and photoreceptors resulting in a feedforward cycle of damage. Signaled by the SASP-chemokines released into the tissue environment, immune cells (monocytes, neutrophils, and T cells) extravasate from the blood vessels, infiltrate the retina, and release SASP components, contributing to a chronic inflammation and other AMD-related pathologies