Impact of nitric oxide's bidirectional role on glaucoma: focus on Helicobacter pylori–related nitrosative stress
Apostolis Papaefthymiou
Department of Gastroenterology, 401 General Military Hospital of Athens, Athens, Greece
Search for more papers by this authorMichael Doulberis
Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorPanagiotis Katsinelos
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorChristos Liatsos
Department of Gastroenterology, 401 General Military Hospital of Athens, Athens, Greece
Search for more papers by this authorStergios A. Polyzos
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
First Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorGeorgios Kotronis
Department of Internal Medicine, Agios Pavlos General Hospital, Thessaloniki, Macedonia, Greece
Search for more papers by this authorKaterina Papanikolaou
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorCorresponding Author
Jannis Kountouras
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Address for correspondence: Professor Jannis Kountouras, Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece. [email protected], [email protected]Search for more papers by this authorApostolis Papaefthymiou
Department of Gastroenterology, 401 General Military Hospital of Athens, Athens, Greece
Search for more papers by this authorMichael Doulberis
Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorPanagiotis Katsinelos
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorChristos Liatsos
Department of Gastroenterology, 401 General Military Hospital of Athens, Athens, Greece
Search for more papers by this authorStergios A. Polyzos
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
First Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorGeorgios Kotronis
Department of Internal Medicine, Agios Pavlos General Hospital, Thessaloniki, Macedonia, Greece
Search for more papers by this authorKaterina Papanikolaou
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Search for more papers by this authorCorresponding Author
Jannis Kountouras
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
Address for correspondence: Professor Jannis Kountouras, Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece. [email protected], [email protected]Search for more papers by this authorAbstract
Nitric oxide (NO), a small molecule generated ubiquitously, targets a plethora of tissues to regulate both physiological and pathophysiological functions. NO overproduction, stimulated by microenvironmental conditions, is the main component that dysregulates the tight balance between its beneficial and damaging roles in ocular homeostasis. Considering the protective functions of NO against glaucoma, its endogenous release facilitates aqueous humor drainage and regulates ocular blood flow, maintaining a normal intraocular pressure. NO overproduction generates free radicals, such as peroxynitrite, which induce a vicious circle of vascular disharmony and dysregulation, transient ischemia, nitrosative stress, neuronal degeneration, and permanent glaucomatic injury. Helicobacter pylori (Hp) is considered a burdening factor of glaucoma. NO overproduction and possible systematic dispersion in Hp infection (Hp-I) could suggest a potential pathophysiological bridge between these conditions. In this review, we aim to elucidate the role of NO in glaucoma with respect to Hp-I, with the aim to stimulate further studies.
References
- 1Asghari, A., M. Hosseini, F. Beheshti, et al. 2018. Inducible nitric oxide inhibitor aminoguanidine, ameliorated oxidative stress, interleukin-6 concentration and improved brain-derived neurotrophic factor in the brain tissues of neonates born from titanium dioxide nanoparticles exposed rats. J. Matern. Neonatal Med. 7058: 1–12.
- 2Bogdan, C. 2001. Nitric oxide and the immune response. Nat. Immunol. 2: 907–916.
- 3Bredt, D.S. & S.H. Snyder. 1994. Nitric oxide: a physiologic messenger molecule. Annu. Rev. Biochem. 63: 175–195.
- 4Brown, G.C. 2010. Nitric oxide and neuronal death. Nitric Oxide 23: 153–165.
- 5Calabrese, V., C. Mancuso, M. Calvani, et al. 2007. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8: 766–775.
- 6Ghimire, K., H.M. Altmann, A.C. Straub, et al. 2017. Nitric oxide: what's new to no? Am. J. Physiol. 312: C254–C262.
- 7Tegeder, I. 2019. Nitric oxide mediated redox regulation of protein homeostasis. Cell. Signal. 53: 348–356.
- 8Panthi, S., S. Manandhar & K. Gautam. 2018. Hydrogen sulfide, nitric oxide, and neurodegenerative disorders. Transl. Neurodegener. 7: 3.
- 9Chong, C.-M., N. Ai, M. Ke, et al. 2018. Roles of nitric oxide synthase isoforms in neurogenesis. Mol. Neurobiol. 55: 2645–2652.
- 10Aliancy, J., W.D. Stamer & B. Wirostko. 2017. A review of nitric oxide for the treatment of glaucomatous disease. Ophthalmol. Ther. 6: 221–232.
- 11Dawson, T.M. & V.L. Dawson. 2018. Nitric Oxide Signaling in Neurodegeneration and Cell Death. 1st ed. Amsterdam: Elsevier Inc.
10.1016/bs.apha.2017.09.003 Google Scholar
- 12Alderton, W.K., C.E. Cooper & R.G. Knowles. 2001. Nitric oxide synthases: structure, function and inhibition. Biochem. J. 357: 593–615.
- 13Toda, N. & M. Nakanishi-Toda. 2007. Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog. Retin. Eye Res. 26: 205–238.
- 14Ghasemi, M., Y. Mayasi, A. Hannoun, et al. 2018. Nitric oxide and mitochondrial function in neurological diseases. Neuroscience 376: 48–71.
- 15Sharma, J.N., A. Al-Omran & S.S. Parvathy. 2007. Role of nitric oxide in inflammatory diseases. Inflammopharmacology 15: 252–259.
- 16Kone, B.C., T. Kuncewicz, W. Zhang, et al. 2003. Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide. Am. J. Physiol. Renal Physiol. 285: F178–90.
- 17MacMicking, J., Q. Xie & C. Nathan. 1997. Nitric oxide and macrophage function. Annu. Rev. Immunol. 15: 323–350.
- 18Straub, A.C., A.W. Lohman, M. Billaud, et al. 2012. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. Nature 491: 473–477.
- 19Schneemann, A., B.G. Dijkstra, T.J. van den Berg, et al. 2002. Nitric oxide/guanylate cyclase pathways and flow in anterior segment perfusion. Graefes Arch. Clin. Exp. Ophthalmol. 240: 936–941.
- 20Moncada, S., R.M. Palmer & E.A. Higgs. 1991. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43: 109–142.
- 21Predescu, D., S. Predescu, J. Shimizu, et al. 2005. Constitutive eNOS-derived nitric oxide is a determinant of endothelial junctional integrity. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L371–81.
- 22Garcia-Calvo, M., H.G. Knaus, O.B. McManus, et al. 1994. Purification and reconstitution of the high-conductance, calcium-activated potassium channel from tracheal smooth muscle. J. Biol. Chem. 269: 676–682.
- 23Moncada, S. & J.P. Bolaños. 2006. Nitric oxide, cell bioenergetics and neurodegeneration. J. Neurochem. 97: 1676–1689.
- 24Pollard, A.K., E.L. Craig & L. Chakrabarti. 2016. Mitochondrial complex 1 activity measured by spectrophotometry is reduced across all brain regions in ageing and more specifically in neurodegeneration. PLoS One 11: e0157405.
- 25Tatarkova, Z., M. Kovalska, V. Timkova, et al. 2016. The effect of aging on mitochondrial complex i and the extent of oxidative stress in the rat brain cortex. Neurochem. Res. 41: 2160–2172.
- 26Coleman, J.W. 2002. Nitric oxide: a regulator of mast cell activation and mast cell-mediated inflammation. Clin. Exp. Immunol. 129: 4–10.
- 27Wink, D.A., I. Hanbauer, M.B. Grisham, et al. 1996. Chemical biology of nitric oxide: regulation and protective and toxic mechanisms. Curr. Top. Cell. Regul. 34: 159–187.
- 28Hara, M.R., N. Agrawal, S.F. Kim, et al. 2005. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat. Cell Biol. 7: 665–674.
- 29Handy, D.E. & J. Loscalzo. 2006. Nitric oxide and posttranslational modification of the vascular proteome: s-nitrosation of reactive thiols. Arterioscler. Thromb. Vasc. Biol. 26: 1207–1214.
- 30Weinreb, R.N., T. Aung & F.A. Medeiros. 2014. The pathophysiology and treatment of glaucoma. JAMA 311: 1901.
- 31Saccà, S.C., S. Gandolfi, A. Bagnis, et al. 2016. From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma. Ageing Res. Rev. 29: 26–41.
- 32Borges-Giampani, A.S. & J. Giampani. 2013. Anatomy of ciliary body, ciliary processes, anterior chamber angle and collector vessels. In Glaucoma—Basic and Clinical Aspects. S. Rumelt, Ed.: IntechOpen.
10.5772/52780 Google Scholar
- 33 American Academy of Ophthalmology. Theories of glaucomatous optic nerve damage. Clinical education: basic & clinical science course. American Academy of Ophthalmology. Cited December 17, 2016. https://www.aao.org/bcscsnippetdetail.aspx?id=f19571e0-b8d7-4679-a2c5-fd30a9b016c1.
- 34Wiederholt, M., H. Thieme & F. Stumpff. 2000. The regulation of trabecular meshwork and ciliary muscle contractility. Prog. Retin. Eye Res. 19: 271–295.
- 35Wiederholt, M., A. Sturm & A. Lepple-Wienhues. 1994. Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide. Invest. Ophthalmol. Vis. Sci. 35: 2515–2520.
- 36Haefliger, I.O., E. Dettmann, R. Liu, et al. 1999. Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma. Surv. Ophthalmol. 43: Suppl 1: S51–S58.
- 37Wiederholt, M. 1998. Nitric oxide and endothelin in aqueous humour outflow regulation. In Nitric Oxide and Endothelin in the Pathogenesis of Glaucoma. I. Haefliger & J. Flammer, Eds.: 68–177. Philadelphia, PA: Lippincott.
- 38Saccà, S.C., S. Gandolfi, A. Bagnis, et al. 2016. The outflow pathway: a tissue with morphological and functional unity. J. Cell. Physiol. 231: 1876–1893.
- 39Ellis, D.Z., W.M. Dismuke & B.M. Chokshi. 2009. Characterization of soluble guanylate cyclase in no-induced increases in aqueous humor outflow facility and in the trabecular meshwork. Investig. Opthalmology Vis. Sci. 50: 1808.
- 40Dismuke, W.M., C.C. Mbadugha & D.Z. Ellis. 2008. NO-induced regulation of human trabecular meshwork cell volume and aqueous humor outflow facility involve the BKCa ion channel. Am. J. Physiol. Cell Physiol. 294: C1378–C1386.
- 41Flammer, J., V.P. Costa, N. Orzalesi, et al. 2002. The impact of ocular blood flow in glaucoma. Prog. Retin. Eye Res. 21: 359–393.
- 42Goto, T., K. Haruma, Y. Kitadai, et al. 1999. Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients. Clin. Cancer Res. 5: 1411–1415.
- 43Fu, S., K.S. Ramanujam, A. Wong, et al. 1999. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology 116: 1319–1329.
- 44Di Lorenzo, A., M.I. Lin, T. Murata, et al. 2014. eNOS-derived nitric oxide regulates endothelial barrier function through VE-cadherin and Rho GTPases. J. Cell Sci. 127: 2120–2120.
- 45Chang, J.Y.H., W.D. Stamer, J. Bertrand, et al. 2015. Role of nitric oxide in murine conventional outflow physiology. Am. J. Physiol. Physiol. 309: C205–C214.
- 46Ellis, D.Z., N.A. Sharif & W.M. Dismuke. 2010. Endogenous regulation of human Schlemm's canal cell volume by nitric oxide signaling. Invest. Ophthalmol. Vis. Sci. 51: 5817–5824.
- 47Szabó, C. & C. Thiemermann. 1995. Regulation of the expression of the inducible isoform of nitric oxide synthase. In Nitric Oxide: Biochemistry, Molecular Biology, and Therapeutic Implication. L. Ignarro & F. Murad, Eds.: 113–153. New York: Academic Press.
10.1016/S1054-3589(08)61083-2 Google Scholar
- 48Dawson, V.L. & T.M. Dawson. 1995. Physiological and toxicological actions of nitric oxide in the central nervous system. In Nitric Oxide: Biochemistry, Molecular Biology, and Therapeutic Implication. L. Ignarro & F. Murad, Eds.: 323–342. New York: Academic Press.
10.1016/S1054-3589(08)61095-9 Google Scholar
- 49Ignarro, L. 1996. Nitric oxide as a communication signal in vascular and neuronal cells. In Nitric Oxide, Principles and Actions. J. Lancaster, Ed.: 111–137. New York: Academic Press.
10.1016/B978-012435555-2/50004-8 Google Scholar
- 50Polak, K., A. Luksch, F. Berisha, et al. 2007. Altered nitric oxide system in patients with open-angle glaucoma. Arch. Ophthalmol. 125: 494–498.
- 51Nathanson, J.A. & M. McKee. 1995. Identification of an extensive system of nitric oxide-producing cells in the ciliary muscle and outflow pathway of the human eye. Invest. Ophthalmol. Vis. Sci. 36: 1765–1773.
- 52Becquet, F., Y. Courtois & O. Goureau. 1997. Nitric oxide in the eye: multifaceted roles and diverse outcomes. Surv. Ophthalmol. 42: 71–82.
- 53Lima, M.G., C. Maximino, K.R. Matos Oliveira, et al. 2014. Nitric oxide as a regulatory molecule in the processing of the visual stimulus. Nitric Oxide 36: 44–50.
- 54Osborne, N.N., N.L. Barnett & A.J. Herrera. 1993. NADPH diaphorase localization and nitric oxide synthetase activity in the retina and anterior uvea of the rabbit eye. Brain Res. 610: 194–198.
- 55Cavet, M.E., J.L. Vittitow, F. Impagnatiello, et al. 2014. Nitric Oxide (NO): an emerging target for the treatment of glaucoma. Investig. Opthalmology Vis. Sci. 55: 5005.
- 56Rokicki, W., M. Żaba, D. Wyględowska-Promieńska, et al. 2015. Inducible and endothelial nitric synthetase expression and nitrotyrosine accumulation in iris vasculature of patients with primary open-angle glaucoma: a pilot study. Med. Sci. Monit. 21: 76–81.
- 57Izzotti, A., S.C. Sacca, A. Bagnis, et al. 2009. Glaucoma and Helicobacter pylori infection: correlations and controversies. Br. J. Ophthalmol. 93: 1420–1427.
- 58Schmetterer, L. & K. Polak. 2001. Role of nitric oxide in the control of ocular blood flow. Prog. Retin. Eye Res. 20: 823–847.
- 59Buys, E.S., Y.-C. Ko, C. Alt, et al. 2013. Soluble guanylate cyclase α1-deficient mice: a novel murine model for primary open angle glaucoma. PLoS One 8: e60156.
- 60Fernández-Durango, R., A. Fernández-Martínez, J. García-Feijoo, et al. 2008. Expression of nitrotyrosine and oxidative consequences in the trabecular meshwork of patients with primary open-angle glaucoma. Investig. Ophthalmol. Vis. Sci. 49: 2506–2511.
- 61Neufeld, A.H., M.R. Hernandez & M. Gonzalez. 1997. Nitric oxide synthase in the human glaucomatous optic nerve head. Arch. Ophthalmol. 115: 497–503.
- 62Resch, H., G. Garhofer, G. Fuchsjäger-Mayrl, et al. 2009. Endothelial dysfunction in glaucoma. Acta Ophthalmol. 87: 4–12.
- 63Waliszek-Iwanicka, A., M. Waliszek, M. Banach, et al. 2010. Assessment of blood flow in posterior ciliary arteries and its correlation with intraocular and arterial blood pressures in patients with open angle glaucoma. Med. Sci. Monit. 16: CR501–CR509.
- 64Haufschild, T., M.R. Tschudi, J. Flammer, et al. 2000. Nitric oxide production by isolated human and porcine ciliary processes. Graefes Arch. Clin. Exp. Ophthalmol. 238: 448–453.
- 65Pianka, P., Y. Oron, M. Lazar, et al. 2000. Nonadrenergic, noncholinergic relaxation of bovine iris sphincter: role of endogenous nitric oxide. Invest. Ophthalmol. Vis. Sci. 41: 880–886.
- 66Haefliger, I.O., J. Flammer & T.F. Lüscher. 1992. Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery. Invest. Ophthalmol. Vis. Sci. 33: 2340–2343.
- 67Stamer, W.D., Y. Lei, A. Boussommier-Calleja, et al. 2011. eNOS, a pressure-dependent regulator of intraocular pressure. Invest. Ophthalmol. Vis. Sci. 52: 9438–9444.
- 68Heyne, G.W., J.A. Kiland, P.L. Kaufman, et al. 2013. Effect of nitric oxide on anterior segment physiology in monkeys. Investig. Opthalmology Vis. Sci. 54: 5103.
- 69Chandrawati, R., J.Y.H. Chang, E. Reina-Torres, et al. 2017. Localized and controlled delivery of nitric oxide to the conventional outflow pathway via enzyme biocatalysis: toward therapy for glaucoma. Adv. Mater. 29: 1–7.
- 70Park, C.H. & J.W. Kim. 2012. Effect of advanced glycation end products on oxidative stress and senescence of trabecular meshwork cells. Korean J. Ophthalmol. 26: 123.
- 71Kashiwagi, K., Y. Iizuka & S. Tsukahara. 2002. Neuroprotective effects of Nipradilol on purified cultured retinal ganglion cells. J. Glaucoma 11: 231–238.
- 72Masuda, K., M. Takase, Y. Kitazawa, et al. 1996. Phase III comparative clinical study on KT 210 in patients with primary open-angle glaucoma and ocular hypertension-multicenter cooperative between-group comparative double-blind clinical trial with 0.5% timolol maleate ophthalmic solution. J. Eye 13: 1771–1785.
- 73Hu, C., J. Sun, Y. Zhang, et al. 2018. Local delivery and sustained-release of nitric oxide donor loaded in mesoporous silica particles for efficient treatment of primary open-angle glaucoma. Adv. Healthc. Mater. 7: 1801047.
- 74Grieshaber, M.C. & J. Flammer. 2007. Does the blood-brain barrier play a role in glaucoma? Surv. Ophthalmol. 52: S115–21.
- 75Kang, J.H., S.J. Loomis, B.L. Yaspan, et al. 2014. Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond). 28: 662–671.
- 76Siu, A.W., M.C.P. Leung, C.H. To, et al. 2002. Total retinal nitric oxide production is increased in intraocular pressure-elevated rats. Exp. Eye Res. 75: 401–406.
- 77Aslan, M., A. Cort & I. Yucel. 2008. Oxidative and nitrative stress markers in glaucoma. Free Radic. Biol. Med. 45: 367–376.
- 78Kaufman, P.L. 1999. Nitric-oxide synthase and neurodegeneration/neuroprotection. Proc. Natl. Acad. Sci. U.S.A. 96: 9455–9456.
- 79Neufeld, A.H., A. Sawada & B. Becker. 1999. Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc. Natl. Acad. Sci. 96: 9944–9948.
- 80Takahata, K., H. Katsuki, T. Kume, et al. 2003. Retinal neurotoxicity of nitric oxide donors with different half-life of nitric oxide release: involvement of N-methyl-D-aspartate receptor. J. Pharmacol. Sci. 92: 428–432.
- 81Morizane, C., K. Adachi, I. Furutani, et al. 1997. N(omega)-nitro-L-arginine methyl ester protects retinal neurons against N-methyl-D-aspartate-induced neurotoxicity in vivo. Eur. J. Pharmacol. 328: 45–49.
- 82Lipton, S.A. & P.A. Rosenberg. 1994. Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med. 330: 613–622.
- 83Jafri, A.J.A., R. Agarwal, I. Iezhitsa, et al. 2018. Protective effect of magnesium acetyltaurate and taurine against NMDA-induced retinal damage involves reduced nitrosative stress. Mol. Vis. 24: 495–508.
- 84Salt, T.E. & M.F. Cordeiro. 2006. Glutamate excitotoxicity in glaucoma: throwing the baby out with the bathwater? Eye 20: 730–731.
- 85Levy, D.I. & S.A. Lipton. 1990. Comparison of delayed administration of competitive and uncompetitive antagonists in preventing NMDA receptor-mediated neuronal death. Neurology 40: 852–855.
- 86Sisk, D.R. & T. Kuwabara. 1985. Histologic changes in the inner retina of albino rats following intravitreal injection of monosodium L-glutamate. Graefes Arch. Clin. Exp. Ophthalmol. 223: 250–258.
- 87Osborne, N.N., J.P. Wood, G. Chidlow, et al. 1999. Ganglion cell death in glaucoma: what do we really know? Br. J. Ophthalmol. 83: 980–986.
- 88Naskar, R. & E.B. Dreyer. 2001. New horizons in neuroprotection. Surv. Ophthalmol. 45: Suppl 3: S250–S255; discussion S273–S276.
- 89Li, J., Z. Lu, L. Xu, et al. 2014. Neuroprotective effects of bis(7)-tacrine in a rat model of pressure-induced retinal ischemia. Cell Biochem. Biophys. 68: 275–282.
- 90Vorwerk, C.K., S.A. Lipton, D. Zurakowski, et al. 1996. Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine. Invest. Ophthalmol. Vis. Sci. 37: 1618–1624.
- 91Ung, L., U. Pattamatta, N. Carnt, et al. 2017. Oxidative stress and reactive oxygen species: a review of their role in ocular disease. Clin. Sci. (Lond). 131: 2865–2883.
- 92Kapin, M.A., R. Doshi, B. Scatton, et al. 1999. Neuroprotective effects of eliprodil in retinal excitotoxicity and ischemia. Invest. Ophthalmol. Vis. Sci. 40: 1177–1182.
- 93Brooks, D.E., G.A. Garcia, E.B. Dreyer, et al. 1997. Vitreous body glutamate concentration in dogs with glaucoma. Am. J. Vet. Res. 58: 864–867.
- 94Carter-Dawson, L., M.L.J. Crawford, R.S. Harwerth, et al. 2002. Vitreal glutamate concentration in monkeys with experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 43: 2633–2637.
- 95Källberg, M.E., D.E. Brooks, K.N. Gelatt, et al. 2007. Endothelin-1, nitric oxide, and glutamate in the normal and glaucomatous dog eye. Vet. Ophthalmol. 10: 46–52.
- 96Manucha, W. 2017. Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity. Clín. Investig. Arterioscler. 29: 92–97.
- 97Lipton, S.A. 2003. Possible role for memantine in protecting retinal ganglion cells from glaucomatous damage. Surv. Ophthalmol. 48: Suppl 1: S38–S46.
- 98Pacher, P., J.S. Beckman & L. Liaudet. 2007. Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 87: 315–424.
- 99Guix, F.X., I. Uribesalgo, M. Coma, et al. 2005. The physiology and pathophysiology of nitric oxide in the brain. Prog. Neurobiol. 76: 126–152.
- 100Lipton, S.A., Y.B. Choi, Z.H. Pan, et al. 1993. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364: 626–632.
- 101Allen, J.B., T. Keng & C. Privalle. 1998. Nitric oxide and peroxynitrite production in ocular inflammation. Environ. Health Perspect. 106: 1145–1149.
- 102Ischiropoulos, H., L. Zhu & J.S. Beckman. 1992. Peroxynitrite formation from macrophage-derived nitric oxide. Arch. Biochem. Biophys. 298: 446–451.
- 103Aslan, M., T.M. Ryan, T.M. Townes, et al. 2003. Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization. J. Biol. Chem. 278: 4194–4204.
- 104Uttenthal, L.O., D. Alonso, A.P. Fernández, et al. 1998. Neuronal and inducible nitric oxide synthase and nitrotyrosine immunoreactivities in the cerebral cortex of the aging rat. Microsc. Res. Tech. 43: 75–88.
10.1002/(SICI)1097-0029(19981001)43:1<75::AID-JEMT11>3.0.CO;2-0 CASPubMedWeb of Science®Google Scholar
- 105Radi, R., J.S. Beckman, K.M. Bush, et al. 1991. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys. 288: 481–487.
- 106Wareham, L.K., E.S. Buys & R.M. Sappington. 2018. The nitric oxide-guanylate cyclase pathway and glaucoma. Nitric Oxide 77: 75–87.
- 107Dogan, S. & M. Aslan. 2011. The role of retinal oxidative and nitrative injury in glaucomatous neurodegeneration. In Glaucoma - Basic and Clinical Concepts. S. Rumelt, Ed.: IntechOpen.
10.5772/18513 Google Scholar
- 108Morgan, J., J. Caprioli & Y. Koseki. 1999. Nitric oxide mediates excitotoxic and anoxic damage in rat retinal ganglion cells cocultured with astroglia. Arch. Ophthalmol. 117: 1524–1529.
- 109Overby, D.R., J. Bertrand, M. Schicht, et al. 2014. The structure of the trabecular meshwork, its connections to the ciliary muscle, and the effect of pilocarpine on outflow facility in mice. Invest. Ophthalmol. Vis. Sci. 55: 3727–3736.
- 110Rohen, J.W., R. Futa & E. Lütjen-Drecoll. 1981. The fine structure of the cribriform meshwork in normal and glaucomatous eyes as seen in tangential sections. Invest. Ophthalmol. Vis. Sci. 21: 574–585.
- 111Tektas, O.-Y. & E. Lütjen-Drecoll. 2009. Structural changes of the trabecular meshwork in different kinds of glaucoma. Exp. Eye Res. 88: 769–775.
- 112Saccà, S.C. & A. Izzotti. 2011. Oxidative stress in anterior segment of primary open angle glaucoma. In Glaucoma - Current Clinical and Research Aspects. P. Gunvant, Ed.: IntechOpen.
- 113Izzotti, A., S.C. Saccà, B. Di Marco, et al. 2008. Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course. Eye (Lond.). 22: 445–453.
- 114Saccà, S.C., M. Centofanti & A. Izzotti. 2012. New proteins as vascular biomarkers in primary open angle glaucomatous aqueous humor. Invest. Ophthalmol. Vis. Sci. 53: 4242–4253.
- 115Gopalakrishna, D., S. Pennington, A. Karaa, et al. 2016. ET-1 stimulates superoxide production by eNOS following exposure of vascular endothelial cells to endotoxin. Shock 46: 60–66.
- 116Chen, W., H. Xiao, A.N. Rizzo, et al. 2014. Endothelial nitric oxide synthase dimerization is regulated by heat shock protein 90 rather than by phosphorylation. PLoS One 9: e105479.
- 117Jeoung, J.W., D.M. Kim, S. Oh, et al. 2017. The relation between endothelial nitric oxide synthase polymorphisms and normal tension glaucoma. J. Glaucoma 26: 1030–1035.
- 118Kang, J.H., J.L. Wiggs, B.A. Rosner, et al. 2010. Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with sex and postmenopausal hormone use. Investig. Opthalmol. Vis. Sci. 51: 971.
- 119Saccà, S.C. & A. Izzotti. 2014. Focus on molecular events in the anterior chamber leading to glaucoma. Cell. Mol. Life Sci. 71: 2197–2218.
- 120Aktan, F. 2004. iNOS-mediated nitric oxide production and its regulation. Life Sci. 75: 639–653.
- 121Jia, Y., S. Jiang, C. Chen, et al. 2019. Caffeic acid phenethyl ester attenuates nuclear factor-KB-mediated inflammatory responses in Müller cells and protects against retinal ganglion cell death. Mol. Med. Rep. 19: 4863–4871.
- 122Erb, C. 2010. Bedeutung des nukleären faktors kappaB für das primäre offenwinkelglaukom - Eine hypothese. Klin. Monbl. Augenheilkd. 227: 120–127.
- 123Agapova, O.A., P.L. Kaufman & M.R. Hernandez. 2006. Androgen receptor and NFkB expression in human normal and glaucomatous optic nerve head astrocytes in vitro and in experimental glaucoma. Exp. Eye Res. 82: 1053–1059.
- 124Ghasemi, M. & A. Fatemi. 2014. Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases. Neurosci. Biobehav. Rev. 45: 168–182.
- 125Dai, Y., R.N. Weinreb, K.Y. Kim, et al. 2011. Inducible nitric oxide synthase-mediated alteration of mitochondrial OPA1 expression in ocular hypertensive rats. Investig. Ophthalmol. Vis. Sci. 52: 2468–2476.
- 126Neufeld, A.H. 2004. Pharmacologic neuroprotection with an inhibitor of nitric oxide synthase for the treatment of glaucoma. Brain Res. Bull. 62: 455–459.
- 127Dawson, T.M. & V.L. Dawson. 2017. Mitochondrial mechanisms of neuronal cell death: potential therapeutics. Annu. Rev. Pharmacol. Toxicol. 57: 437–454.
- 128Fan, J., T.M. Dawson & V.L. Dawson. 2017. Cell Death Mechanisms of Neurodegeneration. Adv. Neurobiol. 15: 403–425.
- 129Fricker, M., A.M. Tolkovsky, V. Borutaite, et al. 2018. Neuronal cell death. Physiol. Rev. 98: 813–880.
- 130Belkhelfa, M., N. Beder, D. Mouhoub, et al. 2018. The involvement of neuroinflammation and necroptosis in the hippocampus during vascular dementia. J. Neuroimmunol. 320: 48–57.
- 131Liu, R., S. Lonergan, E. Steadham, et al. 2019. Effect of nitric oxide and calpastatin on the inhibition of μ-calpain activity, autolysis and proteolysis of myofibrillar proteins. Food Chem. 275: 77–84.
- 132Fleetwood, A.J., M.K.S. Lee, W. Singleton, et al. 2017. Metabolic remodeling, inflammasome activation, and pyroptosis in macrophages stimulated by Porphyromonas gingivalis and its outer membrane vesicles. Front. Cell. Infect. Microbiol. 7: 351.
- 133Hornik, T.C., A. Vilalta & G.C. Brown. 2016. Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis. J. Cell Sci. 129: 65–79.
- 134Zhang, X., L. Jin, Z. Tian, et al. 2019. Nitric oxide inhibits autophagy and promotes apoptosis in hepatocellular carcinoma. Cancer Sci. 110: 1054–1063.
- 135Toyokuni, S., F. Ito, K. Yamashita, et al. 2017. Iron and thiol redox signaling in cancer: an exquisite balance to escape ferroptosis. Free Radic. Biol. Med. 108: 610–626.
- 136Doulberis, M., G. Kotronis, R. Thomann, et al. 2018. Review: impact of Helicobacter pylori on Alzheimer's disease: what do we know so far? Helicobacter 23: e12454.
- 137Kountouras, J., S.A. Polyzos, M. Doulberis, et al. 2018. Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis. Metabolism 87: 18–24.
- 138Pichon, M. & C. Burucoa. 2019. Impact of the gastro-intestinal bacterial microbiome on helicobacter-associated diseases. Healthcare 7: 34.
- 139Blosse, A., P. Lehours, K.T. Wilson, et al. 2018. Helicobacter: inflammation, immunology, and vaccines. Helicobacter 23: e12517.
- 140Karkhah, A., S. Ebrahimpour, M. Rostamtabar, et al. 2019. Helicobacter pylori evasion strategies of the host innate and adaptive immune responses to survive and develop gastrointestinal diseases. Microbiol. Res. 218: 49–57.
- 141Kountouras, J., M. Tsolaki, E. Gavalas, et al. 2006. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 66: 938–940.
- 142Kountouras, J., G. Deretzi, N. Grigoriadis, et al. 2008. Guillain–Barré syndrome. Lancet Neurol. 7: 1080–1081.
- 143Franceschi, F., V. Ojetti, M. Candelli, et al. 2019. Microbes and Alzheimer’ disease: lessons from H. pylori and GUT microbiota. Eur. Rev. Med. Pharmacol. Sci. 23: 426–430.
- 144Romano, C., Z. Li, A. Arendt, et al. 1999. Epitope mapping of anti-rhodopsin antibodies from patients with normal pressure glaucoma. Investig. Ophthalmol. Vis. Sci. 40: 1275–1280.
- 145Gobert, A.P., D.J. McGee, M. Akhtar, et al. 2001. Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival. Proc. Natl. Acad. Sci. U.S.A. 98: 13844–13849.
- 146Justino, M.C., C. Ecobichon, A.F. Fernandes, et al. 2012. Helicobacter pylori has an unprecedented nitric oxide detoxifying system. Antioxid. Redox Signal. 17: 1190–1200.
- 147Henriksnäs, J., C. Atuma, M. Phillipson, et al. 2009. Acute effects of Helicobacter pylori extracts on gastric mucosal blood flow in the mouse. World J. Gastroenterol. 15: 219.
- 148Michetti, M., C.P. Kelly, J.P. Kraehenbuhl, et al. 2000. Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune protection against helicobacter infection in mice. Gastroenterology 119: 109–118.
- 149Gobert, A.P., B.D. Mersey, Y. Cheng, et al. 2002. Cutting edge: urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase. J. Immunol. 168: 6002–6006.
- 150Souza, M., J.A. Moraes, V.N. Da Silva, et al. 2019. Helicobacter pylori urease induces pro-inflammatory effects and differentiation of human endothelial cells: cellular and molecular mechanism. Helicobacter 24: e12573.
- 151Debowski, A.W., S.M. Walton, E.G. Chua, et al. 2017. Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection. PLoS Pathog. 13: e1006464.
- 152Kusters, J.G., A.H.M. van Vliet & E.J. Kuipers. 2006. Pathogenesis of Helicobacter pylori infection. Clin. Microbiol. Rev. 19: 449–490.
- 153Käbisch, R., R.P. Semper, S. Wüstner, et al. 2016. Helicobacter pylori γ-glutamyltranspeptidase induces tolerogenic human dendritic cells by activation of glutamate receptors. J. Immunol. 196: 4246–4252.
- 154Tegtmeyer, N., M. Neddermann, C.I. Asche, et al. 2017. Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagA. Mol. Microbiol. 105: 358–372.
- 155Tsugawa, H., H. Suzuki, H. Saya, et al. 2012. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe 12: 764–777.
- 156Hanada, K., T. Uchida, Y. Tsukamoto, et al. 2014. Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infect. Immun. 82: 4182–4189.
- 157Handa, O., Y. Naito & T. Yoshikawa. 2007. CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling. Biochem. Pharmacol. 73: 1697–1702.
- 158Jung, M.K., S.K. Joo, Y.L. Jin, et al. 2007. Vacuolating cytotoxin in Helicobacter pylori water-soluble proteins upregulates chemokine expression in human eosinophils via Ca2+ influx, mitochondrial reactive oxygen intermediates, and NF-κB activation. Infect. Immun. 75: 3373–3381.
- 159Djekic, A. & A. Müller. 2016. The immunomodulator VacA promotes immune tolerance and persistent Helicobacter pylori infection through its activities on T cells and antigen-presenting cells. Toxins (Basel) 8: 187.
- 160Kao, J.Y., M. Zhang, M.J. Miller, et al. 2010. Helicobacter pylori immune escape is mediated by dendritic cell-induced treg skewing and Th17 suppression in mice. Gastroenterology 138: 1046–1054.
- 161Butcher, L.D., G. den Hartog, P.B. Ernst, et al. 2017. Oxidative stress resulting from Helicobacter pylori infection contributes to gastric carcinogenesis. CMGH 3: 316–322.
- 162Kountouras, J., G. Deretzi, C. Zavos, et al. 2005. Association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy. Eur. J. Neurol. 12: 139–143.
- 163Moran, A.P. & M.M. Prendergast. 2001. Molecular mimicry in Campylobacter jejuni and Helicobacter pylori lipopolysaccharides: contribution of gastrointestinal infections to autoimmunity. J. Autoimmun. 16: 241–256.
- 164Mukherji, S., S. Ramanathan & S. Tarin. 2011. Uveal effusion associated with Campylobacter jejuni infection presenting as bilateral angle closure glaucoma. J. Glaucoma 20: 587–588.
- 165Kountouras, J. 2009. Helicobacter pylori: an intruder involved in conspiring glaucomatous neuropathy. Br. J. Ophthalmol. 93: 1413–1415.
- 166Kountouras, J., N. Mylopoulos, A.G.P. Konstas, et al. 2003. Increased levels of Helicobacter pylori IgG antibodies in aqueous humor of patients with primary open-angle and exfoliation glaucoma. Graefe's Arch. Clin. Exp. Ophthalmol. 241: 884–890.
- 167Kornberg, A.J. & A. Pestronk. 1993. Immune-mediated neuropathies. Curr. Opin. Neurol. 6: 681–687.
- 168Tezel, G., D.P. Edward & M.B. Wax. 1999. Serum autoantibodies to optic nerve head glycosaminoglycans in patients with glaucoma. Arch. Ophthalmol. 117: 917–924.
- 169Izzotti, A. 2010. Mitochondrial damage in the trabecular meshwork of patients with glaucoma. Arch. Ophthalmol. 128: 724.
- 170Boquet, P., V. Ricci, A. Galmiche, et al. 2003. Gastric cell apoptosis and H. pylori: has the main function of VacA finally been identified? Trends Microbiol. 11: 410–413.
- 171Elfvin, A., A. Edebo, P. Hallersund, et al. 2014. Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori-infected humans. World J. Gastrointest. Pathophysiol. 5: 373–379.
- 172Siregar, G.A., S. Halim & V.R. Sitepu. 2015. Serum TNF-a, IL-8, VEGF levels in Helicobacter pylori infection and their association with degree of gastritis. Acta Med. Indones. 47: 120–126.
- 173Siregar, G., D. Sari & T. Sungkar. 2017. Serum VEGF levels in Helicobacter pylori infection and correlation with Helicobacter pylori cagA and vacA genes. Open Access Maced. J. Med. Sci. 5: 137–141.
- 174Kubes, P. & D.N. Granger. 1992. Nitric oxide modulates microvascular permeability. Am. J. Physiol. 262: H611–H615.
- 175Gajda-Derylo, B., T. Stahnke, S. Struckmann, et al. 2019. Comparison of cytokine/chemokine levels in aqueous humor of primary open-angle glaucoma patients with positive or negative outcome following trabeculectomy. Biosci. Rep. 39: BSR20181894.
- 176Saccà, S.C., A. Vagge, A. Pulliero, et al. 2014. Helicobacter pylori infection and eye diseases. Medicine (Baltimore) 93: e216.
- 177Prasad, A., J. Zhu, J.P.J. Halcox, et al. 2002. Predisposition to atherosclerosis by infections: role of endothelial dysfunction. Circulation 106: 184–190.
- 178Liu, N., N. Zhou, N. Chai, et al. 2016. Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer. BMC Cancer 16: 321.
- 179Cherdantseva, L.A., O.V. Potapova, T.V. Sharkova, et al. 2014. Association of Helicobacter pylori and iNOS production by macrophages and lymphocytes in the gastric mucosa in chronic gastritis. J. Immunol. Res. 2014: 762514.
- 180Makristathis, A., E. Rokita, A. Labigne, et al. 1998. Highly significant role of Helicobacter pylori urease in phagocytosis and production of oxygen metabolites by human granulocytes. J. Infect. Dis. 177: 803–806.
- 181Asaka, M., T. Sugiyama, A. Nobuta, et al. 2001. Atrophic gastritis and intestinal metaplasia in Japan: results of a large multicenter study. Helicobacter 6: 294–299.
- 182Katsurahara, M., Y. Kobayashi, M. Iwasa, et al. 2009. Reactive nitrogen species mediate DNA damage in Helicobacter pylori-infected gastric mucosa. Helicobacter 14: 552–558.
- 183Tatemichi, M., T. Sawa, I. Gilibert, et al. 2005. Increased risk of intestinal type of gastric adenocarcinoma in Japanese women associated with long forms of CCTTT pentanucleotide repeat in the inducible nitric oxide synthase promoter. Cancer Lett. 217: 197–202.
- 184Kaise, M., J. Miwa, N. Suzuki, et al. 2007. Inducible nitric oxide synthase gene promoter polymorphism is associated with increased gastric mRNA expression of inducible nitric oxide synthase and increased risk of gastric carcinoma. Eur. J. Gastroenterol. Hepatol. 19: 139–145.
- 185Zhang, S., D. Shi, M. Li, et al. 2019. The relationship between gastric microbiota and gastric disease. Scand. J. Gastroenterol. 54: 391–396.
- 186Lamarque, D., A.P. Moran, Z. Szepes, et al. 2000. Cytotoxicity associated with induction of nitric oxide synthase in rat duodenal epithelial cells in vivo by lipopolysaccharide of Helicobacter pylori: inhibition by superoxide dismutase. Br. J. Pharmacol. 130: 1531–1538.
- 187Kountouras, J., M. Boziki, S.A. Polyzos, et al. 2017. Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis. Free Radic. Res. 51: 73–79.
- 188Arkenau, H.T., D.O. Stichtenoth, J.C. Frölich, et al. 2002. Elevated nitric oxide levels in patients with chronic liver disease and cirrhosis correlate with disease stage and parameters of hyperdynamic circulation. Z. Gastroenterol. 40: 907–913.
- 189Matsumoto, A., K. Ogura, Y. Hirata, et al. 1995. Increased nitric oxide in the exhaled air of patients with decompensated liver cirrhosis. Ann. Intern. Med. 123: 110–113.
- 190Kountouras, J., C. Zavos & D. Chatzopoulos. 2004. Primary open-angle glaucoma: pathophysiology and treatment. Lancet 364: 1311–1312.
- 191Doulberis, M., S.A. Polyzos, A. Papaefthymiou, et al. 2019. Comments to the editor concerning the paper entitled “The microbiome and ophthalmic disease” by Baim et al. Exp. Biol. Med. 244: 430–432.
- 192Kountouras, J., M. Boziki, S.A. Polyzos, et al. 2017. The emerging role of Helicobacter pylori-induced metabolic gastrointestinal dysmotility and neurodegeneration. Curr. Mol. Med. 17: 389–404.
- 193van der Wijk, A.-E., I.M.C. Vogels, C.J.F. van Noorden, et al. 2017. TNFα-induced disruption of the blood–retinal barrier in vitro is regulated by intracellular 3’,5’-cyclic adenosine monophosphate levels. Invest. Ophthalmol. Vis. Sci. 58: 3496–3505.
- 194Gu, X., S.J. Fliesler, Y.-Y. Zhao, et al. 2014. Loss of caveolin-1 causes blood–retinal barrier breakdown, venous enlargement, and mural cell alteration. Am. J. Pathol. 184: 541–555.
- 195Umeda, M., H. Kobayashi, Y. Takeuchi, et al. 2003. High prevalence of Helicobacter pylori detected by PCR in the oral cavities of periodontitis patients. J. Periodontol. 74: 129–134.
- 196Song, Q., T. Lange, A. Spahr, et al. 2000. Characteristic distribution pattern of Helicobacter pylori in dental plaque and saliva detected with nested PCR. J. Med. Microbiol. 49: 349–353.
- 197Kim, H.Y., H.-J. Dhong, S.K. Chung, et al. 2007. Intranasal Helicobacter pylori colonization does not correlate with the severity of chronic rhinosinusitis. Otolaryngol. Neck Surg. 136: 390–395.
- 198Saccà, S.C., A. Pascotto, G.M. Venturino, et al. 2006. Prevalence and treatment of Helicobacter pylori in patients with blepharitis. Invest. Ophthalmol. Vis. Sci. 47: 501–508.
- 199Zavos, C., J. Kountouras, G. Sakkias, et al. 2012. Histological presence of Helicobacter pylori bacteria in the trabeculum and iris of patients with primary open-angle glaucoma. Ophthalmic Res. 47: 150–156.
- 200Seo, J.H., J.W. Lim, J.-H. Yoon, et al. 2009. Proteinase-activated receptor-2 mediates the expression of integrin α5 and β1 in Helicobacter pylori-infected gastric epithelial AGS cells. Digestion 80: 40–49.
- 201Sekiguchi, F., Y. Matsumoto, Y. Maeda, et al. 2012. Biological activity of Helicobacter pylori components in mammalian cells: is it independent of proteinase-activated receptors? J. Physiol. Pharmacol. 63: 571–576.
- 202Kempuraj, D., G.P. Selvakumar, R. Thangavel, et al. 2018. Glia maturation factor and mast cell-dependent expression of inflammatory mediators and proteinase activated receptor-2 in neuroinflammation. J. Alzheimer's Dis. 66: 1117–1129.
- 203Wang, H. & G. Reiser. 2003. Thrombin signaling in the brain: the role of protease-activated receptors. Biol. Chem. 384: 193–202.
- 204Olson, E.E., P. Lyuboslavsky, S.F. Traynelis, et al. 2004. PAR-1 deficiency protects against neuronal damage and neurologic deficits after unilateral cerebral hypoxia/ischemia. J. Cereb. Blood Flow Metab. 24: 964–971.
- 205Junge, C.E., T. Sugawara, G. Mannaioni, et al. 2003. The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc. Natl. Acad. Sci. U.S.A. 100: 13019–13024.
- 206Kountouras, J., N. Mylopoulos, P. Boura, et al. 2001. Relationship between Helicobacter pylori infection and glaucoma. Ophthalmology 108: 599–604.
- 207Kountouras, J., C. Zavos & D. Chatzopoulos. 2003. Helicobacter pylori and glaucoma. Ophthalmology 110: 2433–2434; author reply 2434.
- 208Kountouras, J., C. Zavos & D. Chatzopoulos. 2004. Induction of apoptosis as a proposed pathophysiological link between glaucoma and Helicobacter pylori infection. Med. Hypotheses 62: 378–381.
- 209Kountouras, J., C. Zavos, N. Grigoriadis, et al. 2008. Helicobacter pylori infection as a risk factor for primary open-angle glaucoma. Clin. Experiment. Ophthalmol. 36: 196.