Neuroprotektive Wirkungen von Antidiabetika in der Therapie von Patienten mit Diabetes und Glaukom oder hohem Glaukomrisiko

Zusammenfassung

Das Glaukom ist mit zahlreichen Risikofaktoren und internistischen Erkrankungen wie Diabetes mellitus Typ 2 verbunden. Der Typ-2-Diabetes-mellitus führt peripher und im Gehirn zu neurodegenerativen Veränderungen. Möglicherweise liegt in der Neurodegeneration auch eine Gemeinsamkeit in der Pathophysiologie und Ätiologie beider Erkrankungen. Interessanterweise scheinen zahlreiche Medikamente zur Therapie des Diabetes mellitus unabhängig von der Senkung des Blutzuckers neuroprotektive Eigenschaften aufzuweisen. Obwohl prospektive, randomisierte klinische Studien dazu noch fehlen, scheinen besonders Metformin und Glucagon-like-Peptide-1-Receptor-Agonisten (GLP-1-RA) neuroprotektive Effekte aufzuweisen. Die immer noch sehr häufig eingesetzten Sulfonylharnstoffe (z. B. Glibenclamid, Glimepirid) senken zwar sehr potent den Blutzucker, haben bez. der Neuroprotektion wohl vergleichsweise weniger Effekte. In der vorliegenden Übersicht werden diese unterschiedlich ausgeprägten neuroprotektiven Befunde dargestellt und eine mögliche Differenzialtherapie für Diabetiker mit Glaukom oder erhöhtem Glaukomrisiko in der Praxis diskutiert.

Schlüsselwörter

Glaukom - Neuroophthalmologie - Pharmakologie

Publication History

Received: 16 December 2022

Accepted: 29 March 2023

Article published online:
19 June 2023

• References/Literatur

• 1 Reis TF, Paula JS, Furtado JM. Primary glaucomas in adults: Epidemiology and public health‐A review. Clin Exp Ophthalmol 2022; 50: 128-142 DOI: 10.1111/ceo.14040.
• 2 Zhao D, Cho J, Kim MH. et al. The Association of Blood Pressure and Primary Open-Angle Glaucoma: A Meta-analysis. Am J Ophthalmol 2014; 158: 615-627.e9 DOI: 10.1016/j.ajo.2014.05.029.
• 3 Bonovas S, Peponis V, Filioussi K. Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta-analysis. Diabet Med 2004; 21: 609-614 DOI: 10.1111/j.1464-5491.2004.01173.x.
• 4 Zhou M, Wang W, Huang W. et al. Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis. PLoS One 2014; 9: e102972 DOI: 10.1371/journal.pone.0102972.
• 5 Stein JD, Newman-Casey PA, Talwar N. et al. The Relationship Between Statin Use and Open-Angle Glaucoma. Ophthalmology 2012; 119: 2074-2081 DOI: 10.1016/j.ophtha.2012.04.029.
• 6 Wang S, Bao X. Hyperlipidemia, Blood Lipid Level, and the Risk of Glaucoma: A Meta-Analysis. Invest Ophthalmol Vis Sci 2019; 60: 1028 DOI: 10.1167/iovs.18-25845.
• 7 Bowe A, Grünig M, Schubert J. et al. Circadian Variation in Arterial Blood Pressure and Glaucomatous Optic Neuropathy–A Systematic Review and Meta-Analysis. Am J Hypertens 2015; 28: 1077-1082 DOI: 10.1093/ajh/hpv016.
• 8 Melgarejo JD, Lee JH, Petitto M. et al. Glaucomatous Optic Neuropathy Associated with Nocturnal Dip in Blood Pressure. Ophthalmology 2018; 125: 807-814 DOI: 10.1016/j.ophtha.2017.11.029.
• 9 Li W, Pan J, Wei M. et al. Nonocular Influencing Factors for Primary Glaucoma: An Umbrella Review of Meta-Analysis. Ophthalmic Res 2021; 64: 938-950 DOI: 10.1159/000519247.
• 10 Kapetanakis VV, Chan MPY, Foster PJ. et al. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol 2016; 100: 86-93 DOI: 10.1136/bjophthalmol-2015-307223.
• 11 Chan JW, Chan NC, Sadun AA. Glaucoma as Neurodegeneration in the Brain. Eye Brain 2021; 13: 21-28 DOI: 10.2147/EB.S293765.
• 12 Murphy MC, Conner IP, Teng CY. et al. Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma. Sci Rep 2016; 6: 31464 DOI: 10.1038/srep31464.
• 13 Hu Z, Zhou F, Kaminga AC. et al. Type 2 Diabetes, Fasting Glucose, Hemoglobin A1c Levels and Risk of Primary Open-Angle Glaucoma: A Mendelian Randomization Study. Invest Ophthalmol Vis Sci 2022; 63: 37 DOI: 10.1167/iovs.63.5.37.
• 14 Kim SW, Kang GW. Diabetes mellitus as a risk factor for glaucoma outcome in Korea. Acta Ophthalmol 2017; 95: e662 DOI: 10.1111/aos.13345.
• 15 Kumar DM, Agarwal N. Oxidative Stress in Glaucoma: A Burden of Evidence. J Glaucoma 2007; 16: 334-343 DOI: 10.1097/01.ijg.0000243480.67532.1b.
• 16 Zhao D, Cho J, Kim MH. et al. Diabetes, Fasting Glucose, and the Risk of Glaucoma. Ophthalmology 2015; 122: 72-78 DOI: 10.1016/j.ophtha.2014.07.051.
• 17 Garcia-Martin E, Cipres M, Melchor I. et al. Neurodegeneration in Patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy. J Ophthalmol 2019; 2019: 1825819 DOI: 10.1155/2019/1825819.
• 18 Amato R, Lazzara F, Chou TH. et al. Diabetes Exacerbates the Intraocular Pressure-Independent Retinal Ganglion Cells Degeneration in the DBA/2 J Model of Glaucoma. Invest Ophthalmol Vis Sci 2021; 62: 9 DOI: 10.1167/iovs.62.9.9.
• 19 Channa R, Lee K, Staggers KA. et al. Detecting retinal neurodegeneration in people with diabetes: Findings from the UK Biobank. PLoS One 2021; 16: e0257836 DOI: 10.1371/journal.pone.0257836.
• 20 Dada T. Is Glaucoma a Neurodegeneration caused by Central Insulin Resistance: Diabetes Type 4?. J Curr Glaucoma Pract 2017; 11: 77-79 DOI: 10.5005/jp-journals-10028-1228.
• 21 Faiq M, Sengupta T, Nath M. et al. Ocular manifestations of central insulin resistance. Neural Regen Res 2023; 18: 1139 DOI: 10.4103/1673-5374.355765.
• 22 Al Hussein Al Awamlh S, Wareham LK, Risner ML. et al. Insulin Signaling as a Therapeutic Target in Glaucomatous Neurodegeneration. Int J Mol Sci 2021; 22: 4672 DOI: 10.3390/ijms22094672.
• 23 Ahmed S, El-Sayed MM, Kandeil MA. et al. Empagliflozin attenuates neurodegeneration through antioxidant, anti-inflammatory, and modulation of α-synuclein and Parkin levels in rotenone-induced Parkinsonʼs disease in rats. Saudi Pharm J 2022; 30: 863-873 DOI: 10.1016/j.jsps.2022.03.005.
• 24 Hurley DJ, Irnaten M, OʼBrien C. Metformin and Glaucoma–Review of Anti-Fibrotic Processes and Bioenergetics. Cells 2021; 10: 2131 DOI: 10.3390/cells10082131.
• 25 Sterling J, Hua P, Dunaief JL. et al. Glucagon-like peptide 1 receptor agonist use is associated with reduced risk for glaucoma. Br J Ophthalmol 2023; 107: 215-220 DOI: 10.1136/bjophthalmol-2021-319232.
• 26 Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Nationale VersorgungsLeitlinie Typ-2-Diabetes – Teilpublikation der Langfassung. 02. 2021. Accessed April 28, 2023 at: https://www.leitlinien.de/themen/diabetes/2-auflage
• 27 Cui QN, Stein LM, Fortin SM. et al. The role of glia in the physiology and pharmacology of glucagon‐like peptide‐1: implications for obesity, diabetes, neurodegeneration and glaucoma. Br J Pharmacol 2022; 179: 715-726 DOI: 10.1111/bph.15683.
• 28 Vergroesen JE, Thee EF, Ahmadizar F. et al. Association of Diabetes Medication With Open-Angle Glaucoma, Age-Related Macular Degeneration, and Cataract in the Rotterdam Study. JAMA Ophthalmol 2022; 140: 674 DOI: 10.1001/jamaophthalmol.2022.1435.
• 29 Shao SC, Su YC, Lai EC. et al. Association between sodium glucose co-transporter 2 inhibitors and incident glaucoma in patients with type 2 diabetes: A multi-institutional cohort study in Taiwan. Diabetes Metab 2022; 48: 101318 DOI: 10.1016/j.diabet.2022.101318.
• 30 Su YC, Hung JH, Chang KC. et al. Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients With Type 2 Diabetes in Taiwan. JAMA Netw Open 2022; 5: e2232584 DOI: 10.1001/jamanetworkopen.2022.32584.
• 31 Lin HC, Stein JD, Nan B. et al. Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus. JAMA Ophthalmol 2015; 133: 915 DOI: 10.1001/jamaophthalmol.2015.1440.
• 32 Siddiqui N, Ali J, Parvez S. et al. Linagliptin, a DPP-4 inhibitor, ameliorates Aβ (1 − 42) peptides induced neurodegeneration and brain insulin resistance (BIR) via insulin receptor substrate-1 (IRS-1) in rat model of Alzheimerʼs disease. Neuropharmacology 2021; 195: 108662 DOI: 10.1016/j.neuropharm.2021.108662.
• 33 Wu A, Khawaja AP, Pasquale LR. et al. A review of systemic medications that may modulate the risk of glaucoma. Eye (Lond) 2020; 34: 12-28 DOI: 10.1038/s41433-019-0603-z.
• 34 Zaki MO, El-Desouky S, Elsherbiny DA. et al. Glimepiride mitigates tauopathy and neuroinflammation in P301S transgenic mice: role of AKT/GSK3β signaling. Inflammopharmacology 2022; 30: 1871-1890 DOI: 10.1007/s10787-022-01023-w.
• 35 Zhou B, Shi Y, Fu R. et al. Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne) 2022; 13: 907340 DOI: 10.3389/fendo.2022.907340.