bims-mideyd Biomed News
on Mitochondrial dysfunction in eye diseases
Issue of 2025–03–30
six papers selected by
Rajalekshmy “Raji” Shyam, Indiana University Bloomington
  1. Inhibition of STAT1 alleviates oxidative damage in retinal pigment epithelial cells and exhibits neuroprotective effects in autoimmune optic neuritis by upregulating IFI30 lysosomal thiol reductase.
  2. Advances in the Study of Age-Related Macular Degeneration Based on Cell or Cell-Biomaterial Scaffolds.
  3. Protective effects of carotenoids against blue light induced-cellular damage in human retinal pigment epithelium.
  4. Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review.
  5. Spermidine mitigates blue-light-induced corneal injury by alleviating oxidative stress and restoring autophagy impairment.
  6. Topical Instillation of N-Acetylcysteine and N-Acetylcysteine Amide Impedes Age-Related Lens Opacity in Mice.
  1. Folia Histochem Cytobiol. 2025 Mar 28.
    Inhibition of STAT1 alleviates oxidative damage in retinal pigment epithelial cells and exhibits neuroprotective effects in autoimmune optic neuritis by upregulating IFI30 lysosomal thiol reductase.
    Siqi Ma, Jiajia Yuan.
       INTRODUCTION: . Oxidative damage-induced retinal pigment epithelial (RPE) cell apoptosis and optic nerve inflammation and demyelination are closely related to the pathogenesis of optic neuritis (ON). STAT1 has been found to be activated in the retina and optic nerve of ON rats. Our study aimed to determine whether STAT1 depletion exerts neuroprotective effects against ON in both cellular and animal models.
    MATERIAL AND METHODS: . ARPE-19 cells were stimulated by H₂O₂ to induce oxidative stress, followed by STAT1 and IFI30 silencing. CCK-8 and flow cytometry assays assessed ARPE-19 cell viability and apoptosis. RT-qPCR, Western blotting, DCFH-DA staining, and commercial kits detected the levels of STAT1, IFI30, apoptosis markers, and antioxidant/oxidative markers. CHIP and luciferase reporter assays validated the binding between STAT1 and IFI30 promoter. Female C57BL/6 mice were immunised with myelin oligodendrocyte glycoprotein (MOG) peptide (MOG35-55) to induce experimental autoimmune encephalomyelitis, an animal model of ON. Optic nerve inflammation, demyelination, axonal loss, and retinalganglion cell (RGC) apoptosis in EAE mice after STAT1 knockdown were evaluated via haematoxylin and eosin, luxol fast blue, immunofluorescence, and Brn3a-TUNEL double staining.
    RESULTS: . STAT1 silencing reversed the H₂O₂-induced increase of cell apoptosis and oxidative stress and the decrease in cell viability in ARPE-19 cells. STAT1 bound with the IFI30 promoter region and negatively regulated its expression. IFI30 knockdown antagonised the protection of STAT1 silencing against H₂O₂-induced oxidative stress and apoptosis in ARPE-19 cells. STAT1 depletion alleviated optic nerve inflammation, demyelination, axonal loss, and RGC apoptosis in EAE mice.
    CONCLUSIONS: . STAT1 silencing exhibits neuroprotective effects against ON by upregulating IFI30.
    Keywords:  IFI30; STAT1; apoptosis; inflammation; optic neuritis; oxidative stress; retinal pigment epithelial cells
    DOI:  https://doi.org/10.5603/fhc.104300
  2. Bioengineering (Basel). 2025 Mar 11. pii: 278. [Epub ahead of print]12(3):
    Advances in the Study of Age-Related Macular Degeneration Based on Cell or Cell-Biomaterial Scaffolds.
    Ziming Li, Zhiyong Hu, Zhixian Gao.
      Age-related macular degeneration (AMD), a progressive neurodegenerative disorder affecting the central retina, is pathologically defined by the irreversible degeneration of photoreceptors and retinal pigment epithelium (RPE), coupled with extracellular drusen deposition and choroidal neovascularization (CNV), and AMD constitutes the predominant etiological factor for irreversible vision impairment in adults aged ≥60 years. Cell-based or cell-biomaterial scaffold-based approaches have been popular in recent years as a major research direction for AMD; monotherapy with cell-based approaches typically involves subretinal injection of progenitor-derived or stem cell-derived RPE cells to restore retinal homeostasis. Meanwhile, cell-biomaterial scaffolds delivered to the lesion site by vector transplantation have been widely developed, and the implanted cell-biomaterial scaffolds can promote the reintegration of cells at the lesion site and solve the problems of translocation and discrete cellular structure produced by cell injection. While these therapeutic strategies demonstrate preliminary efficacy, rigorous preclinical validation and clinical trials remain imperative to validate their long-term safety, functional durability, and therapeutic consistency. This review synthesizes current advancements and translational challenges in cell-based and cell-biomaterial scaffold approaches for AMD, aiming to inform future development of targeted interventions for AMD pathogenesis and management.
    Keywords:  age-related macular degeneration; retinal pigment epithelium; stem cells; tissue engineering
    DOI:  https://doi.org/10.3390/bioengineering12030278
  3. Food Sci Biotechnol. 2025 Apr;34(8): 1713-1723
    Protective effects of carotenoids against blue light induced-cellular damage in human retinal pigment epithelium.
    Jong Hoon Won, Dmitri Sitnikov, Jina Hong.
      The retinal pigmented epithelium (RPE) is constantly exposed to visible light, including blue light (BL) that creates reactive oxygen species (ROS), which are harmful to DNA and induce cellular senescence. Carotenoids are recognized for their antioxidant properties, but their protective effect on DNA repair and cellular senescence under BL induced oxidative stress has not been evaluated. After BL irradiation, the positive senescence-associated-β-galactosidase (SA-β-gal) staining, and gene expression of p16 INK4a and p21 Waf/Cip1 were upregulated in ARPE-19 cells. Pretreatment with carotenoids reduced ROS, p-H2A.X nuclear foci, and SA-β-gal positive cells induced by BL irradiation. Furthermore, pretreatment with carotenoids reduced the secretion of IL-6 and VEGF triggered by BL. Since increased senescent cells and secretion of IL-6 and VEGF are involved in age-related macular degeneration pathogenesis, our results support that carotenoid supplementation has a potential role in protecting the eyes from the deleterious effects of excessive BL exposure.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01757-z.
    Keywords:  ARPE-19; Blue-light; Cellular senescence; DNA damage; Oxidative stress
    DOI:  https://doi.org/10.1007/s10068-024-01757-z
  4. Genes (Basel). 2025 Mar 17. pii: 347. [Epub ahead of print]16(3):
    Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review.
    Khaled K Abu-Amero, Bashaer Almadani, Shereen Abualkhair, Syed Hameed, Altaf A Kondkar, Andrea Sollazzo, Angeli Christy Yu, Massimo Busin, Giorgio Zauli.
      Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber's hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA's variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases.
    Keywords:  DNA pathogenic variant; mitochondria; ophthalmology
    DOI:  https://doi.org/10.3390/genes16030347
  5. Exp Eye Res. 2025 Mar 24. pii: S0014-4835(25)00131-9. [Epub ahead of print] 110360
    Spermidine mitigates blue-light-induced corneal injury by alleviating oxidative stress and restoring autophagy impairment.
    Xiang Li, Jiayun Ge, Jiru Zhu, Xin Yu, Dongjie Song, Zongchan Zhang, Yutong Xia, Yanqing Li, Zhitong Chen, Kuangqi Chen, Ye Shen, Jianping Tong.
      This study investigated the protective efficacy of spermidine on corneal epithelium exposed to photodamage from artificial blue light (BL). After six weeks of BL exposure, the rabbit cornea exhibited epithelial injury and delayed wound healing accompanied by downregulation of spermidine, as identified through metabolomic analysis. Pathways related to autophagy and the antioxidant response were implicated in this process. In vitro, spermidine mitigated BL-induced reductions in viability and proliferation of human corneal epithelial cells, decreased cell death, and enhanced colony formation. Spermidine also partially reversed BL-induced mitochondrial dysfunction, oxidative stress and autophagy impairment. Furthermore, topical administration of spermidine eye drops reduced epithelial injury in the rabbit cornea under BL exposure, demonstrating benefits in promoting cell proliferation, accelerating wound healing, and maintaining antioxidant capacity and autophagy.
    Keywords:  autophagy; blue light; corneal epithelium; metabolomics; oxidative stress; spermidine
    DOI:  https://doi.org/10.1016/j.exer.2025.110360
  6. Biomolecules. 2025 Mar 19. pii: 442. [Epub ahead of print]15(3):
    Topical Instillation of N-Acetylcysteine and N-Acetylcysteine Amide Impedes Age-Related Lens Opacity in Mice.
    Hidetoshi Ishida, Yu Sasaki, Teppei Shibata, Hiroshi Sasaki, Bhavana Chhunchha, Dhirendra P Singh, Eri Kubo.
      Cataracts, the leading cause of blindness globally, are caused by oxidative stress and inflammation, which disrupt lens transparency due to increased accumulation of reactive oxygen species (ROS) as well as protein and DNA damage during aging. Using in vitro, ex vivo, and in vivo models, we determined the protective efficacy of N-acetylcysteine amide (NACA) against oxidative stress-induced and aging-induced cataractogenesis. We found that lens epithelial cells exposed to the oxidative stress inducers hydrogen peroxide (H2O2) or tert-butyl hydroperoxide showed significant ROS accumulation and reduced cellular viability. These effects were inhibited by NACA via the suppression of ROS and thioredoxin-interacting protein (Txnip) expression, a regulator of oxidative stress-related cellular damage and inflammation. In ex vivo lens experiments, NACA significantly reduced H2O2-induced lens opacity and preserved lens integrity. Similarly to NACA-treated lenses ex vivo, the integrity and opacity of aged mouse lenses, when topically instilled with NACA, were preserved and reduced, respectively, and are directly related to reduced Txnip and increased thioredoxin (Trx) expression levels. Overall, our findings demonstrated the protective ability of NACA to abate aberrant redox-active pathways, particularly the ROS/TRX/TXNIP axis, thereby preventing cataractogenesis and preserving eye lens integrity and ultimately impeding aging-related cataracts.
    Keywords:  N-acetylcysteine amide; NLRP3 inflammasome; TXNIP; antioxidant therapy; cataract; lens opacity; oxidative stress
    DOI:  https://doi.org/10.3390/biom15030442
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