Aging-US: Senescent secretory phenotype acquisition on retinal epithelial stem cells

Aging-US published a Special Collection on Eye Disease which included "Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells" which reported that loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression.

Age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP). These changes can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs.

Dr. Cesare Mariotti from The Università Politecnica delle Marche said, "Age-related macular degeneration (AMD) is an eye disorder affecting the elderly which can induce an irreversible loss of central visual function."

Age-related macular degeneration (AMD) is one of the most serious and debilitating forms of aging-related eye disease. Smoking, cataract surgery, high BMI and cardiovascular disease are risk factors for AMD, as well as a family history of AMD.

Figure 5. Human p53 and p21 protein expression levels in senescent and young RPESCs. p53 and p21 protein expression levels (A) Western blot analysis (B) and densitometric analysis of blots. Data are mean ± SD of 3 independent experiments. *P = from 0.022 to 0.046. (C) Relative expression levels of mRNA related to p21 and (D) p53 genes in young (P3), pre-senescent (P11) and senescent (P16) RPESCs cells. Data are mean ± SD of 3 independent experiments. *P = from 0.031 to 0.044.

No effective treatment is available for neovascular AMD, while anti-VEGFD is the mainstay of treatment for dry AMD. Neovascular AMD and GA are characterized by RPE dysfunction; formation of large confluent drusen and hyperpigmentation seem to be the initial insult. AMD patients show a different phenotype as well as functional changes such as altered autophagy, mitochondrial dysfunction, and susceptibility to oxidative stress.

A greater understanding of the molecular pathways that are involved in the various stages of AMD would contribute to the development of innovative therapies.

A greater understanding of the molecular pathways that are involved in the various stages of AMD would contribute to the development of innovative therapies.

The Mariotti Research Team concluded in their Aging-US Research Output that RPESCs can undergo replicative senescence, which affects their proliferation and differentiation ability. In addition, they acquired the SASP, which probably compounds the inflammatory RPE microenvironment during AMD development and progression. A greater understanding of the role of RPESCs in AMD pathogenesis is needed to find means to control the disease.

Full Text - https://www.aging-us.com/article/101624/text

Correspondence to: Cesare Mariotti email: mariottiocul@gmail.com

Keywords: AMD, RPESCs, age-related diseases, senescence, inflammation