Download PDF
Klin Monbl Augenheilkd 2018; 235(02): 157-162
DOI: 10.1055/s-0044-101618
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Mitochondriale Dysfunktion und Bedeutung von Coenzym Q10 beim Glaukom

Mitochondrial Dysfunctions and Role of Coenzyme Q10 in Patients with Glaucoma
Carl Erb
1   Augenklinik am Wittenbergplatz, Berlin
,
Katarzyna Konieczka
2   Augenheilkunde, Universität Basel, Schweiz
› Author Affiliations
Further Information

Publication History

eingereicht 14 January 2018

akzeptiert 21 January 2018

Publication Date:
15 February 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die mitochondriale Funktion ist mit zahlreichen Aspekten der Gesundheit des Auges eng verknüpft. Ursächlich für mitochondriale Dysfunktionen scheint ein Ungleichgewicht zwischen der Bildung von Energie und der Menge an freien Radikalen zu sein. Dadurch kommt es neben einem Energiemangel zu einer erhöhten oxidativen Belastung der betroffenen Augengewebe mit der Folge einer Vielzahl von ophthalmologischen Beeinträchtigungen. Dabei wird zwischen primären und sekundären mitochondrialen Augenerkrankungen unterschieden. Primäre mitochondriale Erkrankungen wie bspw. die Leberʼsche hereditäre Optikusatrophie (LHON), die Retinitis pigmentosa und die chronisch progressive externe Ophthalmoplegie sind die Folge von direkten Schädigungen der mitochondrialen Funktion durch defekte Gene auf der mitochondrialen DNA (mtDNA) oder auf der nukleären DNA (nDNA). Demgegenüber sind sekundäre mitochondriale Dysfunktionen vor allem auf Umwelteinflüsse zurückzuführen. In jüngster Zeit häufen sich Hinweise darauf, dass auch mitochondriale Dysfunktionen bei vielen häufig auftretenden Augenerkrankungen wie dem Glaukom, dem „Trockenen Auge“, der diabetischen Retinopathie, der Katarakt und der altersabhängigen Makuladegeneration (AMD) eine wichtige Rolle spielen. Dieser Beitrag fasst den derzeitigen Kenntnisstand zu mitochondrialen Dysfunktionen und zur Rolle von Coenzym Q10 (CoQ10) als mögliche Therapieoption beim Glaukom zusammen.

Abstract

Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leberʼs hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA). In contrast, secondary mitochondrial dysfunctions are caused by environmental factors. In recent years, there has been growing evidence that mitochondrial dysfunctions play an important role in many common eye diseases, such as glaucoma, dry eye, diabetic retinopathy, cataract and age-related macular degeneration (AMD). This article summarises current knowledge of mitochondrial dysfunctions and the role of coenzyme Q10 (CoQ10) as a possible treatment option – with a special focus on glaucoma.

Schlüsselwörter

Glaukom - Mitochondrien - Coenzym Q10 - freie Radikale - Elektronentransportkette

Key words

glaucoma - mitochondria - coenzyme Q10 - free radicals - electron transport chain
 

  • Literatur

  • 1 Ohia SE, Opere CA, Leday AM. Pharmacological consequences of oxidative stress in ocular tissues. Mutat Res 2005; 579: 22-36
    CrossrefPubMedGoogle Scholar
  • 2 Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid Med Cell Longev 2016; 2016: 3164734 doi:10.1155/2016/3164734
    PubMedGoogle Scholar
  • 3 Beatty S, Koh H, Phil M. et al. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000; 45: 115-134
    CrossrefPubMedGoogle Scholar
  • 4 Uchino Y, Kawakita T, Miyazawa M. et al. Oxidative stress induced inflammation initiates functional decline of tear production. PLoS One 2012; 7: e45805 doi:10.1371/journal.pone.0045805
    CrossrefPubMedGoogle Scholar
  • 5 Voet D, Voet JG, Pratt CW. eds. Fundamentals of Biochemistry. 2nd ed.. ed. Indianapolis: John Wiley and Sons; 2006
    Google Scholar
  • 6 Manella CA. The relevance of mitochondrial membrane topology to mitochondrial function. Biochim Biophys Acta 2006; 1762: 140-147
    CrossrefPubMedGoogle Scholar
  • 7 Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956; 11: 298-300
    CrossrefPubMedGoogle Scholar
  • 8 Gerschman R, Gilbert DL, Nye SW. et al. Influence of x-irradiation on oxygen poisoning in mice. Proc Soc Exp Biol Med 1954; 86: 27-29
    CrossrefPubMedGoogle Scholar
  • 9 Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82: 47-95
    CrossrefPubMedGoogle Scholar
  • 10 Brand MD. The sites and topology of mitochondrial superoxide production. Exp Gerontol 2010; 45: 466-472
    CrossrefPubMedGoogle Scholar
  • 11 Cui H, Kong Y, Zhang H. Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012; 2012: 646354 doi:10.1155/2012/646354
    PubMedGoogle Scholar
  • 12 Seen S, Tong L. Dry eye disease and oxidative stress. Acta Ophthalmol 2017; DOI: 10.1111/aos.13526.
    CrossrefPubMedGoogle Scholar
  • 13 Feher J, Kovacs I, Artico M. et al. Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging 2006; 27: 983-993
    CrossrefPubMedGoogle Scholar
  • 14 Kong GY, Van Bergen NJ, Trounce IA. et al. Mitochondrial dysfunction and glaucoma. J Glaucoma 2009; 18: 93-100
    CrossrefPubMedGoogle Scholar
  • 15 Calderon GD, Juarez OH, Hernandez GE. et al. Oxidative stress and diabetic retinopathy: development and treatment. Eye (Lond) 2017; 31: 1122-1130
    CrossrefPubMedGoogle Scholar
  • 16 Abu-Amero KK, Morales J, Bosley TM. Mitochondrial abnormalities in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2006; 47: 2533-2541
    CrossrefPubMedGoogle Scholar
  • 17 Khawaja AP, Cooke Bailey JN, Kang JH. et al. Assessing the association of mitochondrial genetic variation with primary open-angle glaucoma using gene-set analyses. Invest Ophthalmol Vis Sci 2016; 57: 5046-5052
    CrossrefPubMedGoogle Scholar
  • 18 Benoist dʼAzy C, Pereira B, Chiambaretta F. et al. Oxidative and anti-oxidative stress markers in chronic glaucoma: a systematic review and meta-analysis. PLoS One 2016; 11: e0166915 doi:10.1371/journal.pone.0166915
    CrossrefPubMedGoogle Scholar
  • 19 Kamel K, Farrell M, OʼBrien C. Mitochondrial dysfunction in ocular disease: Focus on glaucoma. Mitochondrion 2017; 35: 44-53
    CrossrefPubMedGoogle Scholar
  • 20 Zhao J, Wang S, Zhong W. et al. Oxidative stress in the trabecular meshwork (Review). Int J Mol Med 2016; 38: 995-1002
    CrossrefPubMedGoogle Scholar
  • 21 McElnea EM, Quill B, Docherty NG. et al. Oxidative stress, mitochondrial dysfunction and calcium overload in human lamina cribrosa cells from glaucoma donors. Mol Vis 2011; 17: 1182-1191
    PubMedGoogle Scholar
  • 22 Tezel G. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 2006; 25: 490-513
    CrossrefPubMedGoogle Scholar
  • 23 Mittag TW, Danias J, Pohorenec G. et al. Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model. Invest Ophthalmol Vis Sci 2000; 41: 3451-3459
    PubMedGoogle Scholar
  • 24 Tatton WG, Chalmers-Redman RM, Sud A. et al. Maintaining mitochondrial membrane impermeability. An opportunity for new therapy in glaucoma?. Surv Ophthalmol 2001; 45 (Suppl.) S277-S283
    CrossrefPubMedGoogle Scholar
  • 25 Alvarado JA, Yeh RF, Franse-Carman L. et al. Interactions between endothelia of the trabecular meshwork and of Schlemmʼs canal: a new insight into the regulation of aqueous outflow in the eye. Trans Am Ophthalmol Soc 2005; 103: 148-162
    PubMedGoogle Scholar
  • 26 Saccà SC, Izzotti A. Focus on molecular events in the anterior chamber leading to glaucoma. Cell Mol Life Sci 2014; 71: 2197-2218
    CrossrefPubMedGoogle Scholar
  • 27 He Y, Ge J, Tombran-Tink J. Mitochondrial defects and dysfunction in calcium regulation in glaucomatous trabecular meshwork cells. Invest Ophthalmol Vis Sci 2008; 49: 4912-4922
    CrossrefPubMedGoogle Scholar
  • 28 Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004; 1660: 171-199
    CrossrefPubMedGoogle Scholar
  • 29 Nucci C, Tartaglione R, Cerulli A. et al. Retinal damage caused by high intraocular pressure-induced transient ischemia is prevented by coenzyme Q10 in rat. Int Rev Neurobiol 2007; 82: 397-406
    PubMedGoogle Scholar
  • 30 Davis BM, Tian K, Pahlitzsch M. et al. Topical coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension. Mitochondrion 2017; 36: 114-123 doi:10.1016/j.mito.2017.05.010
    CrossrefPubMedGoogle Scholar
  • 31 Postorino EI, Rania L, Aragona E. et al. Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye. Eur J Ophthalmol 2017; DOI: 10.5301/ejo.5001011.
    CrossrefPubMedGoogle Scholar
  • 32 Fogagnolo P, Sacchi M, Ceresara G. et al. The effects of topical coenzyme Q10 and vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate after cataract surgery: a clinical and in vivo confocal study. Ophthalmologica 2013; 229: 26-31
    CrossrefPubMedGoogle Scholar
  • 33 Blasi MA, Bovina C, Carella G. et al. Does coenzyme Q10 play a role in opposing oxidative stress in patients with age-related macular degeneration?. Ophthalmologica 2001; 215: 51-54
    PubMedGoogle Scholar
  • 34 Ates O, Bilen H, Keles S. et al. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy. Int J Ophthalmol 2013; 6: 675-679
    PubMedGoogle Scholar
  • 35 Zhang J, Wang S. Topical use of coenzyme Q10-loaded liposomes coated with trimethyl chitosan: tolerance, precorneal retention and anti-cataract effect. Int J Pharm 2009; 372: 66-75
    CrossrefPubMedGoogle Scholar
  • 36 Gueven N, Woolley K, Smith J. Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10. Redox Biol 2015; 4: 289-295
    CrossrefPubMedGoogle Scholar
  • 37 Qu J, Kaufman Y, Washington I. Coenzyme Q10 in the human retina. Invest Ophthalmol Vis Sci 2009; 50: 1814-1818
    CrossrefPubMedGoogle Scholar
  • 38 Qu J, Ma L, Washington I. Retinal coenzyme Q10 in the bovine eye. Biofactors 2011; 37: 393-398 doi:10.1002/biof.166
    CrossrefPubMedGoogle Scholar
  • 39 Fato R, Bergami C, Leoni S. et al. Coenzyme Q10 vitreous levels after administration of coenzyme Q10 eyedrops in patients undergoing vitrectomy. Acta Ophthalmol 2010; 88: e150-e151
    CrossrefPubMedGoogle Scholar
  • 40 Hirano T, Iseki K. Interaction of coenzyme Q10 with the intestinal drug transporter P-glycoprotein. J Agric Food Chem 2008; 56: 6923-6927
    CrossrefPubMedGoogle Scholar
  • 41 Wu JHY, Ward NC, Indrawan AP. et al. Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. Clin Chem 2007; 53: 511-519
    CrossrefPubMedGoogle Scholar
  • 42 Lulli M, Witort E, Papucci L. et al. Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage. Invest Ophthalmol Vis Sci 2012; 53: 8295-8302
    CrossrefPubMedGoogle Scholar
  • 43 Lee D, Shim MS, Kim KY. et al. Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated mitochondrial alteration in a mouse model of glaucoma. Invest Ophthalmol Vis Sci 2014; (55) 993-1005
    PubMedGoogle Scholar
  • 44 Parisi V, Centofanti M, Gandolfi S. et al. Effects of coenzyme Q10 in conjunction with vitamin E on retinal-evoked and cortical-evoked responses in patients with open-angle glaucoma. J Glaucoma 2014; 23: 391-404
    CrossrefPubMedGoogle Scholar