Retinal pigment epithelium cell senescence (RPE senescence)

Retinal pigment epithelium (RPE) cell senescence refers to a stable state of cell cycle arrest in RPE cells, often triggered by chronic oxidative stress, DNA damage, or telomere shortening (PubMed: 31465846). These senescent cells undergo profound phenotypic changes, including the accumulation of lipofuscin and the development of a senescence-associated secretory phenotype (SASP), which involves the release of pro-inflammatory cytokines and growth factors (PubMed: 33408240). In the context of the eye, RPE senescence is a critical driver of age-related macular degeneration (AMD), as the loss of functional RPE cells leads to the secondary death of photoreceptors and vision loss (PubMed: 30545902). Therapeutic interventions currently under investigation include senolytics, which aim to selectively eliminate these dysfunctional cells, and senomorphics, which seek to suppress their harmful inflammatory secretions (Nature Medicine, 2015). Targeting this process represents a novel approach to treating degenerative retinal diseases by addressing the underlying cellular aging mechanisms rather than just the symptoms. While promising, the clinical application of these therapies requires careful management of potential off-target effects on healthy ocular tissues.

Other names

RPE cell senescenceSenescence of retinal pigment epithelial cellsCellular senescence in RPE

Senolytics selectively induce apoptosis in senescent cells by inhibiting pro-survival pathways (SCAPs) such as BCL-2 family proteins or PI3K/AKT signaling (PubMed: 25749138). Senomorphics act by suppressing the expression or secretion of pro-inflammatory SASP factors (PubMed: 33408240).