Aging-US: RPE cell senescence in age-related macular degeneration
09-08-2021Aging-US published a Special Collection on Eye Disease which included "HMGB1 and Caveolin-1 related to RPE cell senescence in age-related macular degeneration" and reported that AMD is a major unmet medical need as it is estimated that more than 20 million patients will be affected by 2050 in the US alone.
STGD is the most common hereditary macular dystrophy, mostly affecting young patients aged between 6 and 15 years old with a prevalence of 1/8,000-1/10,000. It is formed by the reaction of 2 all-trans retinal molecules with phosphatidylethanolamine generating N-retinylidene-PE, as a detoxication mechanism of retinal isomers including all-trans and 11-cis-retinal. Indeed, it has been shown that as early as in 3-month-old Abca4-/- Rdh8-/- mice, the amplitudes of scotopic A and B waves and flicker ERG are reduced.
Dr. Jin Yang and Dr. Xiaorong Li both from The Tianjin Medical University Eye Hospital said, "Age-related macular degeneration (AMD) is the leading cause of vision loss in older adults worldwide."
"Age-related macular degeneration (AMD) is the leading cause of vision loss in older adults worldwide."
AMD can be classified into early-stage or late-stage AMD. The latter is characterized by neovascularization, geographic atrophy, or both. Conversely, early-stage AMD is characterized by a limited amount of drusen, which is mainly caused by lipid and protein accumulation and thought to contribute to atrophic changes.
As the disease progresses, neovascular changes or geographic atrophy involving the macular area can be present in patients for years. Therefore, the authors explored the relationship between dry AMD and RPE dysfunction and senescence using proteomic mass spectrometry to examine differential expression in induced pluripotent stem cell-derived RPE cell lines with and without A2E treatment. They have previously demonstrated that the iPSC-derived RPE is phenotypically and functionally similar to the native RPE. In addition, the young status of iPSC-RPE may provide an excellent means for observing changes in protein expression during the process of RPE cell aging.
A2E photo-oxidation products can cause oxidative stress, membrane permeation, telomere dysfunction and accelerated RPE senescence. Although A2E is clearly present in the retina, there are rather different opinions regarding its distribution. Ablonczy et al. showed that levels of A2E decreased from the periphery to the centre region in aging tissue of macaques and humans but A2E was localized mainly in the centre region of young mouse retina.
Figure 6. Glycyrrhizic acid alleviated A2E induced cell senescence. (A) An MTT assay was performed on RPE cells treated with different concentrations of GA. Data are presented as means ± SD; * indicates a p value < 0.05, ** indicates a p value < 0.01, n=3. (B)The release of HMGB1 induced by different concentrations of A2E+BL with or without 100μM GA were detected by ELISA assays. Data are presented as means ± SD; * indicates a p value < 0.05, ** indicates a p value < 0.01, n=3. (C) Representative microscopic images of β-galactosidase staining in RPE cells induced by different concentrations of A2E+BL with or without 100μM GA. (D) Quantification of percentage of cells with positive SA-β-gal staining. Data are presented as means ± SD; * indicates a p value < 0.05, ** indicates a p value < 0.01, n=3. (E) Proposed schematic model for strategies for HMGB1 inhibition in response to A2E treatment.
The Yang/Li Research Team concluded in their Aging-US Research Output, "upregulation of HMGB1 and Caveolin-1 caused RPE cell senescence and suppressed migration and invasion, and β-catenin and Zo-1 accumulation was enhanced by A2E in RPE cells. In particular, the results showed a change in expression of HMGB1 and Caveolin-1, which suggests that they are prime gatekeepers in RPE cell senescence. The above results indicate that stabilizing expression of HMGB1 and Caveolin-1 is a potential therapeutic target to prevent the progression of RPE cell senescence."
Full Text - https://www.aging-us.com/article/102039/text
Correspondence to: Jin Yang email: yangjinchina324@gmail.com and Xiaorong Li email: lixiaorong@tmu.edu.cn
Keywords: A2E, HMGB1, Caveolin-1, RPE cell senescence, AMD
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The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.
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