bims-mideyd 2025-01-19 papers

Sci Rep. 2025 Jan 11. 15(1): 1715

Passion fruit seed extract protects hydrogen peroxide-induced cell damage in human retinal pigment epithelium ARPE-19 cells.

Haruka Uozumi, Shinpei Kawakami, Yuko Matsui, Sadao Mori, Akira Sato.

Age-related macular degeneration (AMD) is a major cause of vision loss among adults. We investigated the protective effects of passion fruit seed extract (PFSE) and its rich polyphenol piceatannol in an AMD cell model in which human retinal pigment epithelial ARPE-19 cells were exposed to hydrogen peroxide (H2O2). Using a cell viability WST-8 assay, we revealed that PFSE and piceatannol increased the cellular viability of ARPE-19 cells by 130% and 133%, respectively. Moreover, PFSE and piceatannol recovered the cell viability of ARPE-19 cells, which had decreased to 60% owing to H2O2-induced damage, to approximately 84% and 89%, respectively. In addition, we found that the treatment of ARPE-19 cells with H2O2 decreased the mitochondrial and glycolytic ATP production rate to approximately 54% that of healthy control ARPE-19 cells using a Seahorse extracellular flux analyzer. Furthermore, pretreatment with PFSE and piceatannol restored the oxidative stress-induced decrease in the mitochondrial and glycolytic ATP production rate to approximately 97% and 82%, respectively. These results indicated the cytoprotective effects of PFSE and piceatannol against oxidative stress in human ARPE-19 cells by resolving the dysfunction of mitochondrial and glycolytic energy metabolism.

Keywords: ARPE-19 cells; Age-related macular degeneration; Functional food; Hydrogen peroxide; Mitochondrial function; Oxidative stress; Passion fruit seed extract; Piceatannol

DOI: https://doi.org/10.1038/s41598-025-85158-0

Graefes Arch Clin Exp Ophthalmol. 2025 Jan 15.

Long-term cultivation of retinal pigment epithelium cells on nanofiber scaffolds.

Julian A Zimmermann, Lucy Irlenbusch, Uwe Hansen, Marcus Himmler, Chun Zeng, Nicole Eter, Thomas Fuchsluger, Peter Heiduschka.

PURPOSE: The retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age-related macular degeneration (AMD) and other retinal degenerative diseases. The introduction of healthy RPE cell cultures into the subretinal space offers a potential treatment strategy. The aim of this study was the long-term culture and characterisation of RPE cells on nanofiber scaffolds.
METHODS: Nanofiber scaffolds consisting of polycaprolactone (PCL) and collagen were prepared by electrospinning. Porcine RPE cell cultures were maintained on PCL scaffolds, PCL-collagen scaffolds, and controls at the bottom of 24-well plates. Cell culture analysis was performed by immunohistochemistry, while the release of inflammatory cytokines IL-6, IL-8, TNF-α, and PDGF-β was measured by ELISA and multiplex assays. Ultrastructural features were examined by transmission electron microscopy.
RESULTS: The observation period averaged 42.7 weeks for controls, 38.7 weeks for PCL scaffold cultures, and 36.1 weeks for PCL-collagen scaffold cultures, with cell number and morphology remaining stable. TNF-α levels in the supernatants were minimal, IL-6 levels were consistently low, and IL-8 levels decreased from initially high to lower levels over time.
CONCLUSION: RPE cells were stably cultured on nanofiber scaffolds for extended periods of time. The long-term physiological properties of RPE cells, including phagocytic ability and visual cycle enzyme activity, need to be further investigated before clinical application. In addition, controlling the expression of inflammatory mediators is a major challenge. Despite these hurdles, overcoming them is critical given the increasing prevalence of retinal degenerative diseases.

Keywords: Cell culture; Cell replacement; Macular degeneration; Nanofiber scaffolds; Porcine retinal pigment epithelium

DOI: https://doi.org/10.1007/s00417-024-06707-3

Cornea. 2025 Jan 17.

Mitochondria-Targeted Antioxidant (MitoQ) and Nontargeted Antioxidant (Idebenone) Mitigate Mitochondrial Dysfunction in Corneal Endothelial Cells.

Myriam Böhm, Mohit Parekh, Neha Deshpande, Queenie Cheung, Nathan Shatz, Varun Kumar, Ula V Jurkunas.

PURPOSE: To investigate the effectiveness of mitochondrial-targeted antioxidant mitoquinone (MitoQ) and nontargeted antioxidant idebenone (Idb) in alleviating mitochondrial dysfunction in corneal endothelial cells (CEnCs).
METHODS: In vitro experiments were conducted using immortalized normal human corneal endothelial cells (HCEnC-21T; SVN1-67F) and Fuchs endothelial corneal dystrophy (FECD) cells (SVF5-54F; SVF3-76M). Cells were pretreated with MitoQ or Idb and then exposed to menadione (MN) with simultaneous antioxidant treatment. Mitochondrial parameters were evaluated through adenosine triphosphate viability assays, JC-1 staining for mitochondrial membrane potential, and Tom-20 antibody staining for fragmentation, with analysis performed using ImageJ software. HCEnC-21T cells were additionally exposed to ultraviolet-A (25 J/cm2) to assess drug effects under physiological stress. Mitochondrial fragmentation in FECD specimens was analyzed pre- and post-treatment with the drugs. Statistical analysis was conducted using 1-/2-way analysis of variance with post-hoc Tukey test.
RESULTS: MitoQ and Idb enhanced cell viability and mitochondrial membrane potential in both normal and FECD cells under MN-induced stress. Idb reduced MN-induced mitochondrial fragmentation by 32% more than MitoQ in HCEnC-21T cells and by 13% more in SVF5-54F cells. Under ultraviolet-A stress, Idb and MitoQ improved mitochondrial function by 31% and 25%, respectively, with MitoQ increasing mitochondrial function by 42% in FECD specimens.
CONCLUSIONS: Differential responses in mitochondrial dysfunction across cell lines highlight disease heterogeneity. MitoQ and Idb protected CEnCs from oxidative stress and improved mitochondrial bioenergetics, suggesting that mitochondrial-targeted antioxidants could be considered for mitochondrial dysfunction in CEnCs.

DOI: https://doi.org/10.1097/ICO.0000000000003801

Exp Eye Res. 2025 Jan 10. pii: S0014-4835(25)00011-9. [Epub ahead of print] 110240

Accumulation of autophagosomes in aging human photoreceptor cell synapses.

Tapas C Nag.

Autophagy is common in the aging retinal pigment epithelium (RPE). A dysfunctional autophagy in aged RPE is implicated in the pathogenesis of age-related macular degeneration. Aging human retina accompanies degenerative changes in photoreceptor mitochondria. It is not known how the damaged mitochondria are handled by photoreceptor cells with aging. This study examined donor human retinas (age: 56-94 years; N=12) by transmission electron microscopy to find mitochondrial dynamics and status of autophagy in macular photoreceptor cells. Observations were compared between the relatively lower age (56-78 years) and aged retinas (80-94 years). Mitochondrial fusion was predominant in photoreceptor inner segments (ellipsoids), but rarely seen in the synaptic terminals. Also, fusion became widespread with progressive aging in ellipsoids (12% and 21% between rods and cones at tenth decade, respectively). More importantly, it was found that the photoreceptor synaptic mitochondria altered significantly with aging (swelling and loss of cristae), compared to those in ellipsoids that became dark and condensed. The damaged synaptic mitochondria were sequestered inside autophagosomes, whose frequency was higher in aged photoreceptors, being 34% in cone and 24% in rod terminals, at tenth decade. However, autolysosomes/residual bodies were rare, and thus the aged photoreceptor synaptic terminals harboured many autophagosomes, the possible reasons for which are discussed. Such age-related altered mitochondrial population and defective autophagy in synaptic terminals may influence photoreceptor survival in late aging.

Keywords: Retina; aging; autophagy; mitochondria; photoreceptor cells; synapses

DOI: https://doi.org/10.1016/j.exer.2025.110240