Pleiotrope Effekte in der lokalen medikamentösen Glaukomtherapie

 

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Zusammenfassung

Neben der klassischen Augeninnendrucksenkung kommen zunehmend auch ergänzende Therapiestrategien für die Behandlung eines Glaukoms infrage. Aus diesem Grund gewinnen pleiotrope Wirkungen von Medikamenten, das sind positive Nebeneffekte unabhängig von ihrer Hauptwirkung, immer mehr an Bedeutung und haben in der Inneren Medizin bereits einen therapeutischen Stellenwert. Anhand der lokalen Antiglaukomatosa Betablocker, Alpha-2-Agonisten, Carboanhydrasehemmer und Prostaglandin-Analoga soll deren bisher bekanntes pleiotropes Spektrum vorgestellt und diskutiert werden.

Abstract

In glaucoma treatment, beside the traditional reduction of intraocular pressure, additional therapeutic strategies have come into consideration. Therefore pleiotropic effects of medications, defined as positively acting effects independent of the main mechanism of action, represent a new research sub-field in medical therapy and play an increasingly important role in internal medicine. Using the example of local beta-blockers, alpha-2-agonists, carbonic anhydrase inhibitors and prostaglandin analogues, their pleiotropic spectra will be shown and discussed.

• Literatur

• 1 European Glaucoma Society. Terminologie und Handlungsrichtlinien zum Glaukom: Klassifikation und Terminologie. Editrice DOGMA; 2007: 119
  CrossrefGoogle Scholar
• 2 Caprioli J, Garway-Heath DF. International Glaucoma Think Tank. A critical reevaluation of current glaucoma management: International Glaucoma Think Tank, July 27–29, 2006, Taormina, Sicily. Ophthalmology 2007; 114: S1-S41
  CrossrefPubMedGoogle Scholar
• 3 Mao LK, Stewart WC, Shields MB. Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am J Ophthalmol 1991; 111: 51-55
  PubMedGoogle Scholar
• 4 Shirakashi M, Iwata K, Sawaguchi S et al. Intraocular pressure-dependent progression of visual field loss in advanced primary open-angle glaucoma: a 15-year follow-up. Ophthalmologica 1993; 207: 1-5
  CrossrefPubMedGoogle Scholar
• 5 Leske MC, Heijl A, Hyman L et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology 2007; 114: 1965-1972
  CrossrefPubMedGoogle Scholar
• 6 Erb C, Gast U, Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1593-1601
  CrossrefPubMedGoogle Scholar
• 7 Lin HC, Chien CW, Hu CC et al. Comparison of comorbid conditions between open-angle glaucoma patients and a control cohort: a case-control study. Ophthalmology 2010; 117: 2088-2095
  CrossrefPubMedGoogle Scholar
• 8 Bonomi L, Marchini G, Marraffa M et al. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology 2000; 107: 1287-1293
  CrossrefPubMedGoogle Scholar
• 9 Newman-Casey PA, Talwar N, Nan B et al. The relationship between components of metabolic syndrome and open-angle glaucoma. Ophthalmology 2011; 118: 1318-1326
  PubMedGoogle Scholar
• 10 Tanaka C, Yamazaki Y, Yokoyama H. Study on the progression of visual field defect and clinical factors in normal-tension glaucoma. Jpn J Ophthalmol 2001; 45: 117
  PubMedGoogle Scholar
• 11 Reitsamer HA, Bogner B, Nischler C et al. Biologische und physikalische Aspekte des Augendrucks. Klin Monatsbl Augenheilkd 2011; 228: 97-102
  Article in Thieme ConnectPubMedGoogle Scholar
• 12 Göbel K, Rüfer F, Erb C. Physiologie der Kammerwasserproduktion sowie der Tagesdruckschwankungen und deren Bedeutung für das Glaukom. Klin Monatsbl Augenheilkd 2011; 228: 104-108
  Article in Thieme ConnectPubMedGoogle Scholar
• 13 Gemenetzi M, Yang Y, Lotery AJ. Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment. Eye 2012; 26: 355-369
  CrossrefPubMedGoogle Scholar
• 14 De Moraes CG, Liebmann JM, Greenfield DS et al. Risk factors for visual field progression in the low-pressure glaucoma treatment study. Am J Ophthalmol 2012; 154: 702-711
  CrossrefPubMedGoogle Scholar
• 15 Stein JD, Kim DS, Niziol LM et al. Differences in rates of glaucoma among Asian Americans and other racial groups, and among various Asian ethnic groups. Ophthalmology 2011; 118: 1031-1037
  CrossrefPubMedGoogle Scholar
• 16 Marcus MW, de Vries MM, Junoy Montolio FG et al. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology 2011; 118: 1989-1994
  CrossrefPubMedGoogle Scholar
• 17 Fernandez-Bahamonde JL, Roman-Rodriguez C, Fernandez-Ruiz MC. Central corneal thickness as a predictor of visual field loss in primary open angle glaucoma for a Hispanic population. Semin Ophthalmol 2011; 26: 28-32
  CrossrefPubMedGoogle Scholar
• 18 Leske MC. Ocular perfusion pressure and glaucoma: clinical trial and epidemiologic findings. Curr Opin Ophthalmol 2009; 20: 73-78
  CrossrefPubMedGoogle Scholar
• 19 Welge-Lüssen U, Birke K. [Oxidative stress in the trabecular meshwork of POAG]. Klin Monatsbl Augenheilkd 2010; 227: 99-107
  Article in Thieme ConnectPubMedGoogle Scholar
• 20 Wax MB, Tezel G. Immunoregulation of retinal ganglion cell fate in glaucoma. Exp Eye Res 2009; 88: 825-830
  CrossrefPubMedGoogle Scholar
• 21 Erb C, Heinke M. Oxidative stress in primary open-angle glaucoma. Front Biosci (Elite Ed) 2011; 3: 1524-1533
  PubMedGoogle Scholar
• 22 Almasieh M, Wilson AM, Morquette B et al. The molecular basis of retinal ganglion cell death in glaucoma. Prog Retin Eye Res 2012; 31: 152-181
  CrossrefPubMedGoogle Scholar
• 23 Izzotti A, Saccà SC, Di Marco B et al. Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course. Eye (Lond) 2008; 22: 445-453
  CrossrefPubMedGoogle Scholar
• 24 Saccà SC, LaMaestra S, Micale RT et al. Ability of dorzolamide hydrochloride and timolol maleate to target mitochondria in glaucoma therapy. Arch Ophthalmol 2011; 129: 48-55
  CrossrefPubMedGoogle Scholar
• 25 Miyamoto N, Izuni H, Miyamoto R et al. Nipradilol and timolol induce Foxa3a and peroxiredoxin 2 expression and protect trabecular meshwork cells from oxidative stress. Invest Ophthalmol Vis Sci 2009; 50: 2777-2784
  CrossrefPubMedGoogle Scholar
• 26 Melena J, Osborne NN. Metipranolol attenuates lipid peroxidation in rat brain: a comparative study with other antiglaucoma drugs. Graefes Arch Clin Exp Ophthalmol 2003; 241: 827-833
  CrossrefPubMedGoogle Scholar
• 27 Wood JP, Schmidt KG, Melena J et al. The beta-adrenoceptor antagonists metipranolol and timolol are retinal neuroprotectants: comparison with betaxolol. Exp Eye Res 2003; 76: 505-516
  CrossrefPubMedGoogle Scholar
• 28 Melena J, Wood JP, Osborne NN. Betaxolol, a beta-1-adrenoceptor antagonist, has an affinity for L-type Ca2+ channels. Eur J Pharmacol 1999; 378: 317-322
  CrossrefPubMedGoogle Scholar
• 29 Melena J, Stanton D, Osborne NN. Comparative effects of antiglaucoma drugs on voltage-dependent calcium channels. Graefes Arch Clin Exp Ophthalmol 2001; 239: 522-530
  CrossrefPubMedGoogle Scholar
• 30 Chidlow G, Melena J, Osborne NN. Betaxolol, a beta(1)-adrenoceptor antagonist, reduces Na(+) influx into cortical synaptosomes by direct interaction with Na(+) channels: comparison with other beta-adrenoceptor antagonists. Br J Pharmacol 2000; 130: 759-766
  CrossrefPubMedGoogle Scholar
• 31 Cheon EW, Park CH, Kang SS et al. Nitric oxide synthase expression in the transient ischemic rat retina: neuroprotection of betaxolol. Neurosci Lett 2002; 330: 265-269
  CrossrefPubMedGoogle Scholar
• 32 Endo S, Tomita H, Ishiguro S et al. Effect of betaxolol on aspartate aminotransferase activity in hypoxic rat retina in vitro. Jpn J Pharmacol 2002; 90: 121-124
  CrossrefPubMedGoogle Scholar
• 33 Bonaccorso C, Micale N, Ettari R et al. Glutamate binding-site ligands of NMDA receptors. Curr Med Chem 2011; 18: 5483-5506
  CrossrefPubMedGoogle Scholar
• 34 Baptiste DC, Hartwick ATE, Jollimore CAB et al. Comparison of the neuroprotective effects of adrenoceptor drugs in retinal cell culture and intact retina. Invest Ophthalmol Vis Sci 2002; 43: 2666-2676
  PubMedGoogle Scholar
• 35 Osborne NN, DeSanties L, Bae JH et al. Topically applied betaxolol attenuates NMDA-induced toxicity to ganglion cells and the effects of ischaemia to the retina. Exp Eye Res 1999; 69: 331-342
  CrossrefPubMedGoogle Scholar
• 36 Nagata T, Ueno S, Morita H et al. Direct inhibition of N-methyl-D-aspartate (NMDA)-receptor function by antiglaucomatous β-antagonists. J Pharmacol Sci 2008; 106: 423-434
  CrossrefPubMedGoogle Scholar
• 37 Wood JP, DeSantis L, Chao HM et al. Topically applied betaxolol attenuates ischaemia-induced effects to the rat retina and stimulates BDNF mRNA. Exp Eye Res 2001; 72: 79-86
  CrossrefPubMedGoogle Scholar
• 38 Yu DY, Su EN, Cringle SJ et al. Effect of betaxolol, timolol and nimodipine on human and pig retinal arterioles. Exp Eye Res 1998; 67: 73-81
  CrossrefPubMedGoogle Scholar
• 39 Dong Y, Ishikawa H, Wu Y et al. Effect and mechanism of betaxolol and timolol on vascular relaxation in isolated rabbit ciliary artery. Jpn J Ophthalmol 2006; 50: 504-508
  CrossrefPubMedGoogle Scholar
• 40 Chao HM, Chidlow G, Melena J et al. An investigation into the potential mechanisms underlying the neuroprotective effect of clonidine in the retina. Brain Res 2000; 877: 47-57
  CrossrefPubMedGoogle Scholar
• 41 Saylor M, McLoon LK, Harrison AR et al. Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent. Arch Ophthalmol 2009; 127: 402-406
  CrossrefPubMedGoogle Scholar
• 42 Hong SJ, Wu KY, Wang HZ et al. Effects of commercial antiglaucoma drugs to glutamate-induced [Ca2+]i increase in cultured neuroblastoma cells. J Ocular Pharmacol Ther 2003; 19: 205-215
  CrossrefPubMedGoogle Scholar
• 43 Dong CJ, Guo Y, Agey P et al. Alpha2 adrenergic modulation of NMDA receptor function as a major mechanism of RGC protection in experimental glaucoma and retinal excitotoxicity. Invest Ophthalmol Vis Sci 2008; 49: 4515-4522
  CrossrefPubMedGoogle Scholar
• 44 Lee D, Kim KY, Noh YH et al. Brimonidine blocks glutamate excitotoxicity-induced oxidative stress and preserves mitochondrial transcription factor a in ischemic retinal injury. PLoS One 2012; 7: e47098
  CrossrefPubMedGoogle Scholar
• 45 Ozdemir G, Tolun FI, Gul M et al. Retinal oxidative stress induced by intraocular hypertension in rats may be ameliorated by brimonidine treatment and N-acetyl cysteine supplementation. J Glaucoma 2009; 18: 662-665
  CrossrefPubMedGoogle Scholar
• 46 Prokosch V, Panagis L, Volk GF et al. Alpha2-adrenergic receptors and their core involvement in the process of axonal growth in retinal explants. Invest Ophthalmol Vis Sci 2010; 51: 6688-6699
  CrossrefPubMedGoogle Scholar
• 47 Krupin T, Liebmann JM, Greenfield DS et al. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol 2011; 151: 671-681
  CrossrefPubMedGoogle Scholar
• 48 Davis RA, Innocenti A, Poulsen S-A et al. Carbonic anhydrase inhibitors: identification of selective inhibitors of the human mitochondrial isozymes VA and VB over the cytosolic isozymes I and II from a natural product-based phenolic library. Bioorg Med Chem 2010; 18: 14-18
  CrossrefPubMedGoogle Scholar
• 49 Reber F, Gersch U, Funk RW. Blockers of carbonic anhydrase can cause increase of retinal capillary diameter, decrease of extracellular and increase of intracellular pH in rat retinal organ culture. Graefes Arch Clin Exp Ophthalmol 2003; 241: 140-148
  CrossrefPubMedGoogle Scholar
• 50 Siesky B, Harris A, Brizendine E et al. Literature review and meta-analysis of topical carbonic anhydrase inhibitors and ocular blood flow. Surv Ophthalmol 2009; 54: 33-46
  CrossrefPubMedGoogle Scholar
• 51 Takahashi A, Masuda A, Sun M et al. Oxidative stress-induced apoptosis is associated with alterations in mitochondrial caspase activity and Bcl-2-dependent alterations in mitochondrial pH(pH_m). Brain Res Bull 2004; 62: 497-504
  CrossrefPubMedGoogle Scholar
• 52 Tezel G, Yang X. Caspase-independent component of retinal ganglion cell death in vitro. Invest Ophthalmol Vis Sci 2004; 45: 4049-4059
  CrossrefPubMedGoogle Scholar
• 53 Schallenberg M, Prokosch V, Thanos S. Regulation of retinal proteome by topical antiglaucomatous eye drops in an inherited glaucoma rat model. PLoS One 2012; 7: e33593
  CrossrefPubMedGoogle Scholar
• 54 Guenoun JM, Baudouin C, Rat P et al. In vitro comparison of cytoprotective and antioxidative effects of latanoprost, travoprost, and bimatoprost on conjunctiva-derived epithelial cells. Invest Ophthalmol Vis Sci 2005; 46: 4594-4599
  CrossrefPubMedGoogle Scholar
• 55 Yu AL, Fuchshofer R, Kampik A et al. Effects of oxidative stress in trabecular meshwork cells are reduced by prostaglandin analogues. Invest Ophthalmol Vis Sci 2008; 49: 4872-4880
  CrossrefPubMedGoogle Scholar
• 56 Thieme H, Schimmat C, Muenzer G et al. Endothelin antagonism: effects of FP receptor agonists prostaglandin F2α and fluprostenol on trabecular meshwork contractility. Invest Ophthalmol Vis Sci 2006; 47: 938-945
  CrossrefPubMedGoogle Scholar
• 57 Piechota A, Polańczyk A, Goraca A. Role of endothelin-1 receptor blockers on hemodynamic parameters and oxidative stress. Pharmacol Rep 2010; 62: 28-34
  PubMedGoogle Scholar
• 58 Erb C. Bedeutung des nukleären Faktors kappaB für das primäre Offenwinkelglaukom – eine Hypothese. Klin Monatsbl Augenheilkd 2010; 227: 120-127
  Article in Thieme ConnectPubMedGoogle Scholar
• 59 Yamagishi R, Aihara M, Araie M. Neuroprotective effects of prostaglandin analogues on retinal ganglion cell death independent of intraocular pressure reduction. Exp Eye Res 2011; 93: 265-270
  CrossrefPubMedGoogle Scholar
• 60 Hernández M, Urcola JH, Vecino E. Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments. Exp Eye Res 2008; 86: 798-806
  CrossrefPubMedGoogle Scholar
• 61 Vidal L, Díaz F, Villena A et al. Reaction of Müller cells in an experimental rat model of increased intraocular pressure following timolol, latanoprost and brimonidine. Brain Res Bull 2010; 82: 18-24
  CrossrefPubMedGoogle Scholar
• 62 Park HY, Lee NY, Kim JH et al. Intraocular pressure lowering, change of antiapoptotic molecule expression, and neuroretinal changes by dorzolamide 2 %/timolol 0.5 % combination in a chronic ocular hypertension rat model. J Ocul Pharmacol Ther 2008; 24: 563-571
  CrossrefPubMedGoogle Scholar