bims-mideyd Biomed News
on Mitochondrial dysfunction in eye diseases
Issue of 2022‒10‒02
six papers selected by
Raji Shyam
Indiana University Bloomington
  1. Mdm1 ablation results in retinal degeneration by specific intraflagellar transport defects of photoreceptor cells.
  2. Mitochondrial-Endoplasmic Reticulum Communication-Mediated Oxidative Stress and Autophagy.
  3. Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via Nrf2/miR-134-5p/NF-κB signaling pathway.
  4. Angiopoietin-1 Is Required for Vortex Vein and Choriocapillaris Development in Mice.
  5. SIRT1 Protects Against Particulate Matter-Induced Oxidative Stress in Human Corneal and Conjunctival Epithelial Cells.
  6. Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage.
  1. Cell Death Dis. 2022 Sep 28. 13(9): 833
    Mdm1 ablation results in retinal degeneration by specific intraflagellar transport defects of photoreceptor cells.
    Youlim Son, Soo-Jin Kim, Hwa-Young Kim, Junyeop Lee, Jae-Ryong Kim.
      Mouse double minute 1 (Mdm1) might be involved in the function and structure of centrioles and age-related retinal degeneration. However, the mechanism by which Mdm1 deficiency causes retinal degeneration remains unknown. We confirmed that the Mdm1 protein is localized at the connecting cilium (CC) of photoreceptor cells in the retina. The electroretinograms of 6-week-old Mdm1-/- mice revealed decreased vision, which was eventually lost, and outer segment (OS) photoreceptor degeneration was evident on postnatal day 7, with complete loss of the outer nuclear layer (ONL) observed at 35 weeks. Mdm1-/- mouse retinas showed mislocalization of opsins in the photoreceptor cells, indicating particular intraflagellar transport (IFT) defects, and entrapment of the nuclei in the ONL by microvilli of retinal pigment epithelial cells, leading to apoptosis in the ONL. These results suggest that Mdm1 ablation causes specific IFT defects, which prevents the OS from continuously replenishing new discs, resulting in retinal degeneration.
    DOI:  https://doi.org/10.1038/s41419-022-05237-2
  2. Biomed Res Int. 2022 ;2022 6459585
    Mitochondrial-Endoplasmic Reticulum Communication-Mediated Oxidative Stress and Autophagy.
    Xiaoqing Liu, Riaz Hussain, Khalid Mehmood, Zhaoxin Tang, Hui Zhang, Ying Li.
      Oxidative stress is an imbalance between free radicals and the antioxidant system causing overgeneration of free radicals (oxygen-containing molecules) ultimately leading to oxidative damage in terms of lipid peroxidation, protein denaturation, and DNA mutation. Oxidative stress can activate autophagy to alleviate oxidative damage and maintain normal physiological activities of cells by degrading damaged organelles or local cytoplasm. When oxidative stress is not eliminated by autophagy, it activates the apoptosis cascade. This review provides a brief summary of mitochondrial-endoplasmic reticulum communication-mediated oxidative stress and autophagy. Mitochondria and endoplasmic reticulum being important organelles in cells are directly or indirectly connected to each other through mitochondria-associated endoplasmic reticulum membranes and jointly regulate oxidative stress and autophagy. The reactive oxygen species (ROS) produced by the mitochondrial respiratory chain are the main inducers of oxidative stress. Damaged mitochondria can be effectively cleared by the process of mitophagy mediated by PINK1/parkin pathway, Nix/BNIP3 pathways, and FUNDC1 pathway, avoiding excessive ROS production. However, the mechanism of mitochondrial-endoplasmic reticulum communication in the regulation of oxidative stress and autophagy is rarely known. For this reason, this review explores the mutual connection of mitochondria and endoplasmic reticulum in mediating oxidative stress and autophagy through ROS and Ca2+ and aims to provide part of the theoretical basis for alleviating oxidative stress through autophagy mediated by mitochondrial-endoplasmic reticulum communication.
    DOI:  https://doi.org/10.1155/2022/6459585
  3. FASEB J. 2022 Oct;36(10): e22577
    Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via Nrf2/miR-134-5p/NF-κB signaling pathway.
    Han Du, Zixin Huang, Xin Zhou, Xielan Kuang, Chongde Long, Han Tang, Jingshu Zeng, Hao Huang, Huijun Liu, Binbin Zhu, Licheng Fu, Ke Hu, ShuiBin Lin, Hua Wang, Qingjiong Zhang, Jianhua Yan, Huangxuan Shen.
      Oxidative stress-induced damage to and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD); however, the underlying molecular mechanism is not fully understood. Long noncoding RNAs (lncRNAs) have important roles in various biological processes. In this study, using an oxidative damage model in RPE cells, we identified a novel oxidation-related lncRNA named CYLD-AS1. We further revealed that the expression of CYLD-AS1 was increased in RPEs during oxidative stress. Depletion of CYLD-AS1 promoted cell proliferation and mitochondrial function and protected RPE cells against hydrogen peroxide (H2 O2 )-induced damage. Mechanistically, CYLD-AS1 also regulated the expression of NRF2, which is related to oxidative stress, and NF-κB signaling pathway members, which are related to inflammation. Remarkably, these two signaling pathways were mediated by the CYLD-AS1 interactor miR-134-5p. Moreover, exosomes secreted by CYLD-AS1 knockdown RPE cells had a lower proinflammatory effect than those secreted by control cells. In summary, our study revealed that CYLD-AS1 affects the oxidative stress-related and inflammatory functions of RPE cells by sponging miR-134-5p to mediate NRF2/NF-κB signaling pathway activity, suggesting that targeting CYLD-AS1 could be a promising strategy for the treatment of AMD and related diseases.
    Keywords:  AMD; RPE; inflammation; lncRNA; miRNA; oxidative stress
    DOI:  https://doi.org/10.1096/fj.202200887R
  4. Arterioscler Thromb Vasc Biol. 2022 Sep 29. 101161ATVBAHA122318151
    Angiopoietin-1 Is Required for Vortex Vein and Choriocapillaris Development in Mice.
    Pan Liu, Jeremy A Lavine, Amani Fawzi, Susan E Quaggin, Benjamin R Thomson.
      BACKGROUND: The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid.METHODS: Using neural crest-specific Angpt1 knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning.
    RESULTS: Lacking choroidal ANGPT1, neural crest-specific Angpt1 knockout eyes exhibited marked choriocapillaris attenuation and 50% reduction in number of vortex veins, with only 2 vortex veins present in the majority of eyes. Shortly after birth, dilated choroidal vessels resembling human pachyvessels were observed extending from the remaining vortex veins and displacing the choriocapillaris, leading to retinal pigment epithelium dysfunction and subretinal neovascularization similar to that seen in pachychoroid disease.
    CONCLUSIONS: Together, these findings identify a new role for ANGPT1 in ocular vascular development and demonstrate a clear link between vortex vein dysfunction, pachyvessel formation, and disease.
    Keywords:  angiopoietin; choriocapillaris; pachychoroid; polypoidal choroidal vasculopathy; vortex vein
    DOI:  https://doi.org/10.1161/ATVBAHA.122.318151
  5. Invest Ophthalmol Vis Sci. 2022 Sep 01. 63(10): 19
    SIRT1 Protects Against Particulate Matter-Induced Oxidative Stress in Human Corneal and Conjunctival Epithelial Cells.
    Xiangzhe Li, Boram Kang, Youngsub Eom, Jingxiang Zhong, Hyung Keun Lee, Hyo Myung Kim, Jong Suk Song.
      Purpose: Sirtuin1 (SIRT1) as a hot therapeutic target for oxidative stress-associated diseases that has been extensively studied. This study aimed to determine the changes in SIRT1 expression in particulate matter (PM)-induced corneal and conjunctival epithelial cell damage and explore potential drugs to reduce PM-associated ocular surface injury.Methods: Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to an ambient PM sample. Cytotoxicity was evaluated by water-soluble tetrazolium salt-8 assay. SIRT1 expression was measured by Western blot analysis. Reactive oxygen species (ROS) production, cell apoptosis, mitochondrial function, and cell senescence were assessed by using 2',7'-dichlorofluorescein diacetate assay, annexin V apoptosis assay, tetramethylrhodamine ethyl ester assay, and senescence β-galactosidase staining, respectively.
    Results: PM-induced cytotoxicity of HCECs and HCjECs occurred in a dose-dependent manner. Increased ROS production, as well as decreased SIRT1 expression, were observed in HCECs and HCjECs after 200 µg/mL PM exposure. In addition, PM induced oxidative stress-mediated cellular damage, including cell apoptosis, mitochondrial damage, and cell senescence. Interestingly, SRT1720, a SIRT1 activator, increased SIRT1 expression and decreased ROS production and attenuated PM-induced cell damage in HCECs and HCjECs.
    Conclusions: This study determined that SIRT1 was involved in PM-induced oxidative stress in HCECs and HCjECs and found that ROS overproduction may a key factor in PM-induced SIRT1 downregulation. The SIRT1 activator, SRT1720, can effectively upregulate SIRT1 expression and inhibit ROS production, thereby reversing PM-induced cell damage. This study provides a new potential target for clinical treatment of PM-associated ocular surface diseases.
    DOI:  https://doi.org/10.1167/iovs.63.10.19
  6. Sci Rep. 2022 Sep 28. 12(1): 16156
    Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage.
    Mami Kusaka, Tomoko Hasegawa, Hanako Ohashi Ikeda, Yumi Inoue, Sachiko Iwai, Kei Iida, Akitaka Tsujikawa.
      We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-D-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions.
    DOI:  https://doi.org/10.1038/s41598-022-20497-w
This page is being maintained by Thomas Krichel. It was last updated on 2022‒10‒10 at 02:05:42.