Oxidative stress in retinal pigment epithelium impairs stem cells: a vicious cycle in age-related macular degeneration

Mol Cell Biochem. 2021 Sep 17. doi: 10.1007/s11010-021-04258-3. Online ahead of print.ABSTRACTAging, chronic oxidative stress, and inflammation are major pathogenic factors in the development and progression of age-related macular degeneration (AMD) with the loss of retinal pigment epithelium (RPE). The human RPE contains a subpopulation of progenitors (i.e., RPE stem cells-RPESCs) whose role in the RPE homeostasis is under investigation. We evaluated the paracrine effects of mature RPE cells exposed to oxidative stress (H2O2) on RPESCs behavior through co-cultural, morphofunctional, and bioinformatic approaches. RPESCs showed a decline in proliferation, an increase of the senescence-associated β-galactosidase activity, the acquisition of a senescent-like secretory phenotype (SASP), and the reduction of their stemness and differentiation competencies. IL-6 and Superoxide Dismutase 2 (SOD2) seem to be key molecules in RPESCs response to oxidative stress. Our results get insight into stress-induced senescent-associated molecular mechanisms implicated in AMD pathogenesis. The presence of chronic oxidative stress in the microenvironment reduces the RPESCs abilities, inducing and/or maintaining a pro-inflammatory retinal milieu that in turn could affect AMD onset and progression.PMID:34535868 | DOI:10.1007/s11010-021-04258-3
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Source Type: research

Related Links:

CONCLUSION: Currently, there are no proven effective cell-based treatments for retinal diseases, although several trials have investigated potential therapies. These studies reported favorable safety profiles with multiple surgical approaches, with cells derived from multiple sources, and with utilized different immunosuppressive regiments. However, data demonstrating the efficacy and long-term safety are still pending. Nevertheless, "cell therapy" clinics continue to conduct direct-to consumer marketing for non-FDA-approved treatments with potentially blinding complications.PMID:34635174 | DOI:10.1186/s13287-021-02546-9
Source: Cell Research - Category: Cytology Authors: Source Type: research
Mol Cell Biochem. 2021 Sep 17. doi: 10.1007/s11010-021-04258-3. Online ahead of print.ABSTRACTAging, chronic oxidative stress, and inflammation are major pathogenic factors in the development and progression of age-related macular degeneration (AMD) with the loss of retinal pigment epithelium (RPE). The human RPE contains a subpopulation of progenitors (i.e., RPE stem cells-RPESCs) whose role in the RPE homeostasis is under investigation. We evaluated the paracrine effects of mature RPE cells exposed to oxidative stress (H2O2) on RPESCs behavior through co-cultural, morphofunctional, and bioinformatic approaches. RPESCs sh...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out mo...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study sought to investigate the temporal protein expression changes that occur in a human induced pluripotent stem cell (iPSC)-based RPE-EMT model. We utilized multiplexed isobaric tandem mass tag (TMT) labeling followed by high-resolution tandem mass spectrometry for precise and in-depth quantification of the RPE-EMT proteome. We have identified and quantifed 7,937 protein groups in our TMT-based mass spectrometry analysis. We observed a total of 532 proteins that are differentially regulated during RPE-EMT. Further, we integrated our proteomic data with prior transcriptomic (RNA-seq) data to provide additional insig...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research
Conclusion: Cell replacement therapy has great potential for vision restoration. The results obtained from the initial clinical trials are encouraging and indicates its therapeutic benefits. The current status of the therapies suggests that there is a long way to go before these results can be applied to routine clinical practice. Input from the ongoing multicentre clinical trials will give a more refined idea for the future design of clinical- grade protocols to transplant GMP level HLA matched cells.PMID:34348629 | DOI:10.2174/1574888X16666210804112104
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Source Type: research
Curr Stem Cell Res Ther. 2021 Jun 22. doi: 10.2174/1574888X16666210622124555. Online ahead of print.ABSTRACTAs the ocular disorders causing long-term blindness or optical abnormalities of the ocular tissue affect the quality of life of patients to a large extent, awareness of their corresponding pathogenesis and the earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for development of visual impairment to blindness. Accordingly, stem cells, because of their particular competencies, have gained extensive attention for app...
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Source Type: research
More News: Age-Related Macular Degeneration (AMD) | Biochemistry | Stem Cell Therapy | Stem Cells | Vitamin A