bims-mideyd 2024-11-03 papers

Int J Mol Sci. 2024 Oct 10. pii: 10893. [Epub ahead of print]25(20):

Proteomics Analysis on the Effects of Oxidative Stress and Antioxidants on Proteins Involved in Sterol Transport and Metabolism in Human Telomerase Transcriptase-Overexpressing-Retinal Pigment Epithelium Cells.

R Scott Duncan, Andrew Keightley, Adam A Lopez, Conner W Hall, Peter Koulen.

Age-related macular degeneration (AMD) is the most prevalent ocular disease in the elderly, resulting in blindness. Oxidative stress plays a role in retinal pigment epithelium (RPE) pathology observed in AMD. Tocopherols are potent antioxidants that prevent cellular oxidative damage and have been shown to upregulate the expression of cellular antioxidant proteins. Here, we determined whether oxidative stress and tocopherols, using either normal cellular conditions or conditions of sublethal cellular oxidative stress, alter the expression of proteins mediating sterol uptake, transport, and metabolism. Human telomerase transcriptase-overexpressing RPE cells (hTERT-RPE) were used to identify differential expression of proteins resulting from treatments. We utilized a proteomics strategy to identify protein expression changes in treated cells. After the identification and organization of data, we divided the identified proteins into groups related to biological function: cellular sterol uptake, sterol transport and sterol metabolism. Exposure of cells to conditions of oxidative stress and exposure to tocopherols led to similar protein expression changes within these three groups, suggesting that α-tocopherol (αT) and γ-tocopherol (γT) can regulate the expression of sterol uptake, transport and metabolic proteins in RPE cells. These data suggest that proteins involved in sterol transport and metabolism may be important for RPE adaptation to oxidative stress, and these proteins represent potential therapeutic targets.

Keywords: age-relate macular degeneration (AMD); antioxidant; oxidative stress; proteomics; retinal pigment epithelium (RPE); sterol; tocopherol; vitamin E

DOI: https://doi.org/10.3390/ijms252010893

Stem Cell Res Ther. 2024 Oct 31. 15(1): 390

Advances in retinal pigment epithelial cell transplantation for retinal degenerative diseases.

Hang Liu, Suber S Huang, Gopal Lingam, Dan Kai, Xinyi Su, Zengping Liu.

Retinal degenerative diseases are a leading cause of vision loss and blindness globally, impacting millions. These diseases result from progressive damage to retinal pigment epithelial (RPE) cells for which no curative or palliative treatments exist. Cell therapy, particularly RPE transplantation, has emerged as a promising strategy for vision restoration. This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation. We discuss scaffold-free and scaffold-based approaches, including RPE cell suspensions and pre-organized RPE monolayers on biomaterial scaffolds. Key considerations, such as the form and preparation of RPE implants, delivery devices, strategies, and biodegradability of scaffolds, are examined. The article also explores the challenges and opportunities in RPE scaffold development, emphasising the crucial need for functional integration, immunomodulation, and long-term biocompatibility to ensure therapeutic efficacy. We also highlight ongoing efforts to optimise RPE transplantation methods and their potential to address retinal degenerative diseases.

Keywords: Bruch’s membrane; Cell therapy; Cell transplantation; Macular degeneration; Outer blood-retina barrier; Retinal pigment epithelium; Tissue engineering

DOI: https://doi.org/10.1186/s13287-024-04007-5

Biomed Pharmacother. 2024 Oct 27. pii: S0753-3322(24)01468-9. [Epub ahead of print]180 117582

Oleocanthal mitigates CoCl2-induced oxidative damage and apoptosis via regulating MAPK pathway in human retinal pigment epithelial cells.

Ko-Chieh Huang, Yi-Fen Chiang, Mohamed Ali, Shih-Min Hsia.

Retinal hypoxia causes severe visual impairment and dysfunction in retinal pigment epithelial (RPE) cells, triggering a cascade of events leading to cellular apoptosis. Oxidative stress induced by hypoxia plays a significant role in the development of retinal diseases; however, the precise pathogenesis remains unclear. Oleocanthal, a phenolic compound in extra virgin olive oil, is known for its diverse biological properties. This study aims to investigate the potential anti-oxidative effects of oleocanthal against CoCl2-induced hypoxia in ARPE-19 cells. The cell culture model enabled the evaluation of apoptosis, DNA damage, and ROS levels using MTT assay, Western blot, Annexin V/PI staining, JC-1 staining, MitoSOX, H2DCFDA, immunocytochemistry, and comet assays. Our results showed that oleocanthal effectively protected RPE cells against CoCl2-induced damage by enhancing cell viability, reducing DNA damage, and decreasing ROS levels. Moreover, oleocanthal attenuated CoCl2-induced MMP loss by elevating the JC-1 aggregate/monomer ratio. Furthermore, CoCl2-induced cell apoptosis via up-regulating MAPK signaling, while oleocanthal mitigated this effect. These findings shed light on the molecular mechanisms underlying oleocanthal's protection against oxidative stress induced by hypoxia, offering potential insights for the development of novel therapeutic agents for retinal hypoxia.

Keywords: Hypoxia; Oleocanthal; Oxidative stress; RPE

DOI: https://doi.org/10.1016/j.biopha.2024.117582

Antioxidants (Basel). 2024 Oct 17. pii: 1252. [Epub ahead of print]13(10):

AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation.

Seunghwan Choi, Soo-Ho Choi, Tonking Bastola, Keun-Young Kim, Sungsik Park, Robert N Weinreb, Yury I Miller, Won-Kyu Ju.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp-/- mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.

Keywords: AIBP; Müller glia; glaucoma; mitochondria; neuroinflammation; oxidative stress; retinal ganglion cells

DOI: https://doi.org/10.3390/antiox13101252