From Mechanosensitivity to Inflammatory Responses: New Players in the Pathology of Glaucoma

Current Eye Research

Volumn 39, Issue 2, 2014, Pages 105-119

  Križaj, David ^a   Ryskamp, Daniel A ^a   Tian, Ning ^a   Tezel, Gülgün ^b   Mitchell, Claire H ^c   Slepak, Vladlen Z ^d   Shestopalov, Valery I ^d,e,f  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b University of Louisville School of Medicine   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^f VAVILOV INSTITUTE OF GENERAL GENETICS   (Russian Federation)

Author keywords

ATP; Calcium; Cytokines; Glaucoma; Glia; Inflammation; Mechanosensation; Retinal ganglion cells

Indexed keywords

2',3' O ( 4 BENZOYLBENZOYL)ADENOSINE 5' TRIPHOSPHATE; 3 [[5 (2,3 DICHLOROPHENYL) 1H TETRAZOL 1 YL]METHYL]PYRIDINE; ADENOSINE TRIPHOSPHATE; BRILLIANT BLUE; CALCIUM; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM ION; CD3 ANTIGEN; COMPLEMENT; CYTOKINE; INFLAMMASOME; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; ION CHANNEL; MAJOR HISTOCOMPATIBILITY ANTIGEN; MEMBRANE PROTEIN; MRS 2540; PANNEXIN 1; PROTEOME; PURINERGIC P2 RECEPTOR; PURINERGIC P2X RECEPTOR AGONIST; PURINERGIC P2X RECEPTOR ANTAGONIST; PURINERGIC P2X7 RECEPTOR; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANILLOID RECEPTOR 4; ZINC;

ANTIGEN RECOGNITION; APOPTOSIS; CALCIUM TRANSPORT; CELL DEATH; CELL MIGRATION; CELL TYPE; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITE; DIET SUPPLEMENTATION; GLAUCOMA; HUMAN; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INTRAOCULAR HYPERTENSION; INTRAOCULAR PRESSURE; MECHANICAL STRESS; MECHANOTRANSDUCTION; MICROGLIA; MOLECULAR BIOLOGY; MOLECULE; NERVE DEGENERATION; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEOMICS; RECEPTOR UPREGULATION; RETINA; RETINA GANGLION CELL; RETINA NERVE CELL; REVIEW; SELF STIMULATION; ANIMAL; DISEASE MODEL; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; DISEASE MODELS, ANIMAL; GLAUCOMA; HUMANS; INFLAMMATION; MECHANOTRANSDUCTION, CELLULAR; RETINAL GANGLION CELLS; SIGNAL TRANSDUCTION;

EID: 84892958276     PISSN: 02713683     EISSN: 14602202     Source Type: Journal    
DOI: 10.3109/02713683.2013.836541     Document Type: Review

References (190)

1. Harwerth RS, Crawford ML, Frishman LJ, Viswanathan S, Smith 3rd EL, Carter-Dawson L. Visual field defects and neural losses from experimental glaucoma. Prog Retin Eye Res 2002;21:91-125.
2. Jakobs TC, Libby RT, Ben Y, John SW, Masland RH. Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. J Cell Biol 2005;171:313-325.
3. Baltan S, Inman DM, Danilov CA, Morrison RS, Calkins DJ, Horner PJ. Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration. J Neurosci 2010;30:5644-5652.
4. Tezel G. Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences. Prog Retin Eye Res 2006;25:490-513.
5. Quigley HA, Addicks EM. Chronic experimental glaucoma in primates. I. Production of elevated intraocular pressure by anterior chamber injection of autologous ghost red blood cells. Invest Ophthalmol Vis Sci 1980;19:126-136.
6. Umapathy NS, Li W, Mysona BA, Smith SB, Ganapathy V. Expression and function of glutamine transporters SN1 (SNAT3) and SN2 (SNAT5) in retinal Muller cells. Invest Ophthalmol Vis Sci 2005;46:3980-3987.
7. Sullivan RK, Woldemussie E, Macnab L, Ruiz G, Pow DV. Evoked expression of the glutamate transporter GLT-1c in retinal ganglion cells in human glaucoma and in a rat model. Invest Ophthalmol Vis Sci 2006;47:3853-3859.
8. Reichenbach A, Bringmann A. Mu ller cells in the healthy and diseased retina. New York: Springer; 2010. pp xiv, 417.
9. Bonomi L, Marchini G, Marraffa M, Morbio R. The relationship between intraocular pressure and glaucoma in a defined population. Data from the Egna-Neumarkt Glaucoma Study. Ophthalmologica 2001;215:34-38.
10. Blanch RJ, Ahmed Z, Berry M, Scott RA, Logan A. Animal models of retinal injury. Invest Ophthalmol Vis Sci 2012;53: 2913-2920.
11. Nilius B, Owsianik G. Transient receptor potential channelopathies. Pflugers Arch 2010;460:437-450.
12. Christensen AP, Corey DP. TRP channels in mechanosensation: Direct or indirect activation Nat Rev Neurosci 2007;8:510-521.
13. Wiggs JL. The cell and molecular biology of complex forms of glaucoma: Updates on genetic, environmental, and epigenetic risk factors. Invest Ophthalmol Vis Sci 2012;53: 2467-2469.
14. Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol 1991;109:1090-1095.
15. Stamer WD, Acott TS. Current understanding of conventional outflow dysfunction in glaucoma. Curr Opin Ophthalmol 2012;23:135-143.
16. John SW, Smith RS, Savinova OV, Hawes NL, Chang B, Turnbull D, et al. Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Invest Ophthalmol Vis Sci 1998;39:951-962.
17. Chauhan BC, Pan J, Archibald ML, LeVatte TL, Kelly ME, Tremblay F. Effect of intraocular pressure on optic disc topography, electroretinography, and axonal loss in a chronic pressure-induced rat model of optic nerve damage. Invest Ophthalmol Vis Sci 2002;43:2969-2976.
18. Quigley HA. Clinical trials for glaucoma neuroprotection are not impossible. Curr Opin Ophthalmol 2012;23: 144-154.
19. Sharma AK, Rohrer B. Sustained elevation of intracellular cGMP causes oxidative stress triggering calpain-mediated apoptosis in photoreceptor degeneration. Curr Eye Res 2007;32:259-269.
20. Vallazza-Deschamps G, Fuchs C, Cia D, Tessier LH, Sahel JA, Dreyfus H, et al. Diltiazem-induced neuroprotection in glutamate excitotoxicity and ischemic insult of retinal neurons. Doc Ophthalmol 2005;110:25-35.
21. Bezprozvanny I, Hayden MR. Deranged neuronal calcium signaling and Huntington disease. Biochem Biophys Res Commun 2004;322:1310-1317.
22. Wax MB, Tezel G. Immunoregulation of retinal ganglion cell fate in glaucoma. Exp Eye Res 2009;88:825-830.
23. Crish SD, Calkins DJ. Neurodegeneration in glaucoma: Progression and calcium-dependent intracellular mechanisms. Neuroscience 2011;176:1-11.
24. Burgoyne CF. A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma. Exp Eye Res 2011;93:120-132.
25. Xu HP, Chen H, Ding Q, Xie ZH, Chen L, Diao L, et al. The immune protein CD3zeta is required for normal development of neural circuits in the retina. Neuron 2010;65: 503-515.
26. Steele MR, Inman DM, Calkins DJ, Horner PJ, Vetter ML. Microarray analysis of retinal gene expression in the DBA/2J model of glaucoma. Invest Ophthalmol Vis Sci 2006;47: 977-985.
27. Stasi K, Nagel D, Yang X, Wang RF, Ren L, Podos SM, et al. Complement component 1Q (C1Q) upregulation in retina of murine, primate, and human glaucomatous eyes. Invest Ophthalmol Vis Sci 2006;47:1024-1029.
28. Tezel G. TNF-alpha signaling in glaucomatous neurodegeneration. Prog Brain Res 2008;173:409-421.
29. Huang W, Xing W, Ryskamp DA, Punzo C, Krizaj D. Localization and phenotype-specific expression of ryanodine calcium release channels in C57BL6 and DBA/2J mouse strains. Exp Eye Res 2011;93:700-709.
30. Lebrun-Julien F, Duplan L, Pernet V, Osswald I, Sapieha P, Bourgeois P, et al. Excitotoxic death of retinal neurons in vivo occurs via a non-cell-autonomous mechanism. J Neurosci 2009;29:5536-5545.
31. Tezel G. The immune response in glaucoma: A perspective on the roles of oxidative stress. Exp Eye Res 2011;93: 178-186.
32. Delmas P. Polycystins: From mechanosensation to gene regulation. Cell 2004;118:145-148.
33. Eyckmans J, Boudou T, Yu X, Chen CS. A hitchhiker's guide to mechanobiology. Dev Cell 2011;21:35-47.
34. Coulombre AJ, Coulombre JL. The role of intraocular pressure in the development of the chick eye. IV. Corneal curvature. AMA Arch Ophthalmol 1958;59:502-506.
35. Coulombre AJ, Coulombre JL. Lens development. I. Role of the lens in eye growth. J Exp Zool 1964;156:39-47.
36. Vogel V, Sheetz M. Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol 2006;7: 265-275.
37. Morrison JC, Moore CG, Deppmeier LM, Gold BG, Meshul CK, Johnson EC. A rat model of chronic pressure-induced optic nerve damage. Exp Eye Res 1997;64:85-96.
38. del Rio A, Perez-Jimenez R, Liu R, Roca-Cusachs P, Fernandez JM, Sheetz MP. Stretching single talin rod molecules activates vinculin binding. Science 2009;323: 638-641.
39. Stewart AP, Smith GD, Sandford RN, Edwardson JM. Atomic force microscopy reveals the alternating subunit arrangement of the TRPP2-TRPV4 heterotetramer. Biophys J 2010;99:790-797.
40. Quigley HA, Green WR. The histology of human glaucoma cupping and optic nerve damage: Clinicopathologic correlation in 21 eyes. Ophthalmology 1979;86:1803-1830.
41. Danias J, Lee KC, Zamora MF, Chen B, Shen F, Filippopoulos T, et al. Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: Comparison with RGC loss in aging C57/BL6 mice. Invest Ophthalmol Vis Sci 2003;44:5151-5162.
42. Schlamp CL, Li Y, Dietz JA, Janssen KT, Nickells RW. Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric. BMC Neurosci 2006;7:66.
43. Adalbert R, Coleman MP. Axon pathology in age-related neurodegenerative disorders. Neuropathol Appl Neurobiol 2013;39:90-108.
44. Crish SD, Sappington RM, Inman DM, Horner PJ, Calkins DJ. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Proc Natl Acad Sci USA 2010;107:5196-5201.
45. Begg IS, Drance SM. Progress of the glaucomatous process related to recurrent ischaemic changes at the optic disc. Exp Eye Res 1971;11:141.
46. Fechtner RD, Weinreb RN. Mechanisms of optic nerve damage in primary open angle glaucoma. Surv Ophthalmol 1994;39:23-42.
47. Fortune B, Burgoyne CF, Cull GA, Reynaud J, Wang L. Structural and functional abnormalities of retinal ganglion cells measured in vivo at the onset of optic nerve head surface change in experimental glaucoma. Invest Ophthalmol Vis Sci 2012;53:3939-3950.
48. Weber AJ, Harman CD, Viswanathan S. Effects of optic nerve injury, glaucoma, and neuroprotection on the survival, structure, and function of ganglion cells in the mammalian retina. J Physiol 2008;586:4393-4400.
49. Stevens SL, Ciesielski TM, Marsh BJ, Yang T, Homen DS, Boule JL, et al. Toll-like receptor 9: A new target of ischemic preconditioning in the brain. J Cereb Blood Flow Metab 2008;28:1040-1047.
50. Porciatti V, Nagaraju M. Head-up tilt lowers IOP and improves RGC dysfunction in glaucomatous DBA/2J mice. Exp Eye Res 2010;90:452-460.
51. Kong YX, van Bergen N, Bui BV, Chrysostomou V, Vingrys AJ, Trounce IA, et al. Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury. Neurobiol Aging 2012;33:1126 e15-25.
52. Bui BV, He Z, Vingrys AJ, Nguyen CT, Wong VH, Fortune B. Using the electroretinogram to understand how intraocular pressure elevation affects the rat retina. J Ophthalmol 2013;2013:262467.
53. Banitt MR, Ventura LM, Feuer WJ, Savatovsky E, Luna G, Shif O, et al. Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects. Invest Ophthalmol Vis Sci 2013;54: 2346-2352.
54. Weber AJ, Kaufman PL, Hubbard WC. Morphology of single ganglion cells in the glaucomatous primate retina. Invest Ophthalmol Vis Sci 1998;39:2304-2320.
55. Eisenlohr JE, Langham ME, Maumenee AE. Manometric studies of the pressure-volume relationship in living and enucleated eyes of individual human subjects. Br J Ophthalmol 1962;46:536-548.
56. Dastiridou AI, Ginis HS, De Brouwere D, Tsilimbaris MK, Pallikaris IG. Ocular rigidity, ocular pulse amplitude, and pulsatile ocular blood flow: The effect of intraocular pressure. Invest Ophthalmol Vis Sci 2009;50:5718-5722.
57. Pallikaris IG, Kymionis GD, Ginis HS, Kounis GA, Tsilimbaris MK. Ocular rigidity in living human eyes. Invest Ophthalmol Vis Sci 2005;46:409-414.
58. Silver DM, Geyer O. Pressure-volume relation for the living human eye. Curr Eye Res 2000;20:115-120.
59. Wang J, Freeman EE, Descovich D, Harasymowycz PJ, Kamdeu Fansi A, Li G, et al. Estimation of ocular rigidity in glaucoma using ocular pulse amplitude and pulsatile choroidal blood flow. Invest Ophthalmol Vis Sci 2013;54: 1706-1711.
60. Markin VS, Sachs F. Thermodynamics of mechanosensitivity. Phys Biol 2004;1:110-124.
61. Wiggins P, Phillips R. Membrane-protein interactions in mechanosensitive channels. Biophys J 2005;88:880-902.
62. Niittykoski M, Kalesnykas G, Larsson KP, Kaarniranta K, Akerman KE, Uusitalo H. Altered calcium signaling in an experimental model of glaucoma. Invest Ophthalmol Vis Sci 2010;51:6387-6393.
63. Agar A, Li S, Agarwal N, Coroneo MT, Hill MA. Retinal ganglion cell line apoptosis induced by hydrostatic pressure. Brain Res 2006;1086:191-200.
64. Sappington RM, Carlson BJ, Crish SD, Calkins DJ. The microbead occlusion model: A paradigm for induced ocular hypertension in rats and mice. Invest Ophthalmol Vis Sci. 2010;51:207-216.
65. Pang IH, Clark AF. Rodent models for glaucoma retinopathy and optic neuropathy. J Glaucoma 2007;16:483-505.
66. Ryskamp DA, Witkovsky P, Barabas P, Huang W, Koehler C, Akimov NP, et al. The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells. J Neurosci 2011;31:7089-7101.
67. Xia J, Lim JC, Lu W, Beckel JM, Macarak EJ, Laties AM, et al. Neurons respond directly to mechanical deformation with pannexin-mediated ATP release and autostimulation of P2X7 receptors. J Physiol 2012;590:2285-2304.
68. Resta V, Novelli E, Vozzi G, Scarpa C, Caleo M, Ahluwalia A, et al. Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP. Eur J Neurosci 2007;25:2741-2754.
69. Balaratnasingam C, Morgan WH, Bass L, Ye L, McKnight C, Cringle SJ, et al. Elevated pressure induced astrocyte damage in the optic nerve. Brain Res 2008;1244:142-154.
70. Fu CT, Tran T, Sretavan D. Axonal/glial upregulation of EphB/ephrin-B signaling in mouse experimental ocular hypertension. Invest Ophthalmol Vis Sci 2010;51:991-1001.
71. Molnar T, Barabas P, Birnbaumer L, Punzo C, Kefalov V, Krizaj D. Store-operated channels regulate intracellular calcium in mammalian rods. J Physiol 2012;590:3465-3481.
72. Xue T, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, et al. Melanopsin signalling in mammalian iris and retina. Nature 2011;479:67-73.
73. Sappington RM, Sidorova T, Long DJ, Calkins DJ. TRPV1: Contribution to retinal ganglion cell apoptosis and increased intracellular Ca2 with exposure to hydrostatic pressure. Invest Ophthalmol Vis Sci 2009;50:717-728.
74. Frye A, Ryskamp D, Krizaj D. Overstimulation of TRPV4 in vivo induces selective apoptosis of retinal ganglion cells. An acute in vivo experimental model for glaucoma. IOVS Abstr. 2012:Ft. Lauderdale, FL.
75. Loukin S, Zhou X, Su Z, Saimi Y, Kung C. Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force. J Biol Chem 2010;285: 27176-27181.
76. Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nilius B. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 2003; 424:434-438.
77. Matthews BD, Thodeti CK, Tytell JD, Mammoto A, Overby DR, Ingber DE. Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins. Integr Biol (Camb) 2010;2:435-442.
78. Tomita G. The optic nerve head in normal-tension glaucoma. Curr Opin Ophthalmol 2000;11:116-120.
79. Nickells RW, Howell GR, Soto I, John SW. Under pressure: Cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy. Annu Rev Neurosci 2012;35:153-179.
80. Wang SY, Singh K, Lin SC. The association between glaucoma prevalence and supplementation with the oxidants calcium and iron. Invest Ophthalmol Vis Sci 2012;53: 725-731.
81. Huang W, Fileta J, Rawe I, Qu J, Grosskreutz CL. Calpain activation in experimental glaucoma. Invest Ophthalmol Vis Sci 2010;51:3049-3054.
82. Garcia-Valenzuela E, Shareef S, Walsh J, Sharma SC. Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res 1995;61:33-44.
83. Nakagawa T, Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 2000;150:887-894.
84. de Rivero Vaccari JP, Lotocki G, Alonso OF, Bramlett HM, Dietrich WD, Keane RW. Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J Cereb Blood Flow Metab 2009;29:1251-1261.
85. Abulafia DP, de Rivero Vaccari JP, Lozano JD, Lotocki G, Keane RW, Dietrich WD. Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J Cereb Blood Flow Metab 2009;29:534-544.
86. Kanneganti TD, Lamkanfi M, Kim YG, Chen G, Park JH, Franchi L, et al. Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity 2007;26:433-443.
87. Clarke TC, Williams OJ, Martin PE, Evans WH. ATP release by cardiac myocytes in a simulated ischaemia model: Inhibition by a connexin mimetic and enhancement by an antiarrhythmic peptide. Eur J Pharmacol 2009;605: 9-14.
88. Seminario-Vidal L, Kreda S, Jones L, O'Neal W, Trejo J, Boucher RC, et al. Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of rhoand Ca2-dependent signaling pathways. J Biol Chem 2009;284:20638-20648.
89. Ingber DE. From cellular mechanotransduction to biologically inspired engineering: 2009 Pritzker Award Lecture, BMES Annual Meeting October 10, 2009. Ann Biomed Eng 2010;38:1148-1161.
90. Burnstock G. Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction. J Anat 1999;194:335-342.
91. Sadananda P, Shang F, Liu L, Mansfield KJ, Burcher E. Release of ATP from rat urinary bladder mucosa: Role of acid, vanilloids and stretch. Br J Pharmacol 2009;158: 1655-1662.
92. Winters SL, Davis CW, Boucher RC. Mechanosensitivity of mouse tracheal ciliary beat frequency: Roles for Ca2, purinergic signaling, tonicity, and viscosity. Am J Physiol Cell Physiol 2007;292:L614-L624.
93. Wheeler-Schilling TH, Marquordt K, Kohler K, Guenther E, Jabs R. Identification of purinergic receptors in retinal ganglion cells. Brain Res Mol Brain Res 2001;92:177-180.
94. Zhang X, Li A, Ge J, Reigada D, Laties AM, Mitchell CH. Acute increase of intraocular pressure releases ATP into the anterior chamber. Exp Eye Res 2007;85:637-643.
95. Li A, Zhang X, Zheng D, Ge J, Laties AM, Mitchell CH. Sustained elevation of extracellular ATP in aqueous humor from humans with primary chronic angle-closure glaucoma. Exp Eye Res 2011;93:528-533.
96. Reigada D, Lu W, Zhang M, Mitchell CH. Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels. Neurosci 2008;157:396-404.
97. Lu W, Rasmussen C, Gabelt B, Hennes B, Kaufman P, Laties AM, et al. Upregulation of NTPDase 1 in an experimental monkey glaucoma model. Invest Ophthalmol Vis Sci 2007;48:4804 (Abstract).
98. Lu W, Hu H, Laties AM, Sevigney J, Mitchell CH. Upregulation of Retinal NTPDase 1 and vitreal ATP levels in an experimental rat glaucoma model. Invest Ophthalmol Vis Sci 2008;49:ARVO E abstract:869.
99. Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, et al. Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med 2012;18:600-604.
100. Clark AK, Staniland AA, Marchand F, Kaan TK, McMahon SB, Malcangio M. P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide. J Neurosci 2010;30: 573-582.
101. Zhang X, Zhang M, Laties AM, Mitchell CH. Stimulation of P2X7 receptors elevates Ca2 and kills retinal ganglion cells. Invest Ophthalmol Vis Sci 2005;46:2183-2191.
102. Hu H, Lu W, Zhang M, Zhang X, Argall AJ, Patel S, et al. Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo. Exp Eye Res 2010;91:425-432.
103. Mitchell CH, Lu W. Retinal ganglion cells and glaucoma: Traditional patterns and new possibilities. Curr Topics Membr 2008;62:301-322.
104. Mitchell CH, Lu W, Hu H, Zhang X, Reigada D, Zhang M. The P2X(7) receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance. Purinergic Signal 2009;5: 241-249.
105. Newman EA. Propagation of intercellular calcium waves in retinal astrocytes and Muller cells. J Neurosci 2001;21: 2215-2223.
106. Newman EA. Glial cell inhibition of neurons by release of ATP. J Neurosci 2003;23:1659-1666.
107. North RA. Molecular physiology of P2X receptors. Physiol Rev 2002;82:1013-1067.
108. Pelegrin P, Surprenant A. Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 2006;25:5071-5082.
109. Bunse S, Locovei S, Schmidt M, Qiu F, Zoidl G, Dahl G, et al. The potassium channel subunit Kvbeta3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials. Febs J 2009;276:6258-6270.
110. Dubyak GR. Both sides now: Multiple interactions of ATP with pannexin-1 hemichannels. Focus on ''A permeant regulating its permeation pore: Inhibition of pannexin 1 channels by ATP''. Am J Physiol Cell Physiol 2009;296: C235-C241.
111. Bao L, Locovei S, Dahl G. Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Letts 2004; 572:65-68.
112. Seminario-Vidal L, Okada SF, Sesma JI, Kreda SM, van Heusden CA, Zhu Y, et al. Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia. J Biol Chem 2011;286:26277-26286.
113. Xia J, Lim JC, Lu W, Beckel JM, Macarak EJ, Laties AM, et al. Neurons respond directly to mechanical deformation with pannexin-mediated ATP release and autostimulation of P2X7 receptors. J Physiol 2012;590.10: 2285-2304.
114. Dvoriantchikova G, Ivanov D, Panchin Y, Shestopalov VI. Expression of pannexin family of proteins in the retina. FEBS Letts 2006;580:2178-2182.
115. Franke H, Klimke K, Brinckmann U, Grosche J, Francke M, Sperlagh B, et al. P2X(7) receptor-mRNA and -protein in the mouse retina; changes during retinal degeneration in BALBCrds mice. Neurochem Int 2005;47:235-242.
116. Vessey KA, Fletcher EL. Rod and cone pathway signalling is altered in the P2X7 receptor knock out mouse. Plos One 2012;7:290-305.
117. Yang H, Thompson H, Roberts MD, Sigal IA, Downs JC, Burgoyne CF. Deformation of the early glaucomatous monkey optic nerve head connective tissue after acute IOP elevation in 3-D histomorphometric reconstructions. Invest Ophthalmol Vis Sci 2011;52:345-363.
118. Vanden Abeele F, Bidaux G, Gordienko D, Beck B, Panchin YV, Baranova AV, et al. Functional implications of calcium permeability of the channel formed by pannexin J Cell Biol 2006;174:535-546.
119. Locovei S, Wang J, Dahl G. Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett 2006;580:239-244.
120. Poornima V, Madhupriya M, Kootar S, Sujatha G, Kumar A, Bera AK. P2X7 receptor-pannexin 1 hemichannel association: Effect of extracellular calcium on membrane permeabilization. J Mol Neurosci 2012;46:585-594.
121. Pelegrin P, Barroso-Gutierrez C, Surprenant A. P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage. J Immunol 2008; 180:7147-7157.
122. Silverman WR, de Rivero Vaccari JP, Locovei S, Qiu F, Carlsson SK, Scemes E, et al. The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J Biol Chem 2009;284:18143-18151.
123. Striedinger K, Petrasch-Parwez E, Zoidl G, Napirei M, Meier C, Eysel UT, et al. Loss of connexin36 increases retinal cell vulnerability to secondary cell loss. Eur J Neurosci 2005;22:605-616.
124. Orellana JA, Saez PJ, Shoji KF, Schalper KA, Palacios- Prado N, Velarde V, et al. Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration. Antioxid Redox Signal 2009;11:369-399.
125. Contreras JE, Sanchez HA, Eugenin EA, Speidel D, Theis M,Willecke K, et al. Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc Natl Acad Sci USA 2002;99:495-500.
126. Bao L, Locovei S, Dahl G. Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett 2004; 572:65-68.
127. Barbe MT, Monyer H, Bruzzone R. Cell-cell communication beyond connexins: The pannexin channels. Physiology (Bethesda) 2006;21:103-114.
128. Brough D, Pelegrin P, Rothwell NJ. Pannexin-1-dependent caspase-1 activation and secretion of IL-1beta is regulated by zinc. Eur J Immunol 2009;39:352-358.
129. Scemes E, Spray DC. Extracellular K() and astrocyte signaling via connexin and pannexin channels. Neurochem Res 2012;37:2310-2316.
130. Dvoriantchikova G, Ivanov D, Barakat D, Grinberg A, Wen R, Slepak VZ, Shestopalov VI. Genetic ablation of Pannexin1 protects retinal neurons from ischemic injury. PlosOne 2012;7:e31991.
131. Bargiotas P, Krenz A, Hormuzdi SG, Ridder DA, Herb A, Barakat W, et al. Pannexins in ischemia-induced neurodegeneration. Proc Natl Acad Sci USA 2011;108: 20772-20777.
132. Zhang L, Deng T, Sun Y, Liu K, Yang Y, Zheng X. Role for nitric oxide in permeability of hippocampal neuronal hemichannels during oxygen glucose deprivation. J Neurosci Res 2008;86:2281-2291.
133. Orellana JA, Hernandez DE, Ezan P, Velarde V, Bennett MV, Giaume C, et al. Hypoxia in high glucose followed by reoxygenation in normal glucose reduces the viability of cortical astrocytes through increased permeability of connexin 43 hemichannels. Glia 2010;58:329-343.
134. Domercq M, Perez-Samartin A, Aparicio D, Alberdi E, Pampliega O, Matute C. P2X7 receptors mediate ischemic damage to oligodendrocytes. Glia 2009;58:730-740.
135. Bargiotas P, Monyer H, Schwaninger M. Hemichannels in cerebral ischemia. Curr Mol Med 2009;9:186-194.
136. Thompson RJ, Zhou N, MacVicar BA. Ischemia opens neuronal gap junction hemichannels. Science 2006;312: 924-927.
137. Pelegrin P, Surprenant A. The P2X(7) receptor-pannexin connection to dye uptake and IL-1beta release. Purinergic Signal 2009;5:129-137.
138. Locovei S, Scemes E, Qiu F, Spray DC, Dahl G. Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett 2007;581:483-488.
139. Iglesias R, Locovei S, Roque A, Alberto AP, Dahl G, Spray DC, et al. P2X7 receptor-Pannexin1 complex: Pharmacology and signaling. Am J Physiol Cell Physiol 2008;295: C752-C760.
140. Orellana JA, Froger N, Ezan P, Jiang JX, Bennett MV, Naus CC, et al. ATP and glutamate released via astroglial connexin43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J Neurochem 2011;118:826-840.
141. Pelegrin P, Surprenant A. Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem 2007;282:2386-2394.
142. Ziegler G, Harhausen D, Schepers C, Hoffmann O, Rohr C, Prinz V, et al. TLR2 has a detrimental role in mouse transient focal cerebral ischemia. Biochem Biophys Res Commun 2007;359:574-579.
143. Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, et al. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci USA 2007;104:13798-13803.
144. Shibuya E, Meguro A, Ota M, Kashiwagi K, Mabuchi F, Iijima H, et al. Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma. Invest Ophthalmol Vis Sci 2008;49:4453-4457.
145. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996; 274:782-784.
146. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003;114:181-190.
147. Zhang Z, Trautmann K, Schluesener HJ. Microglia activation in rat spinal cord by systemic injection of TLR3 and TLR7/8 agonists. J Neuroimmunol 2005;164: 154-160.
148. Shiose S, Chen Y, Okano K, Roy S, Kohno H, Tang J, et al. Toll-like receptor 3 is required for development of retinopathy caused by impaired all-trans-retinal clearance in mice. J Biol Chem 2011;286:15543-15555.
149. Luo C, Yang X, Kain AD, Powell DW, Kuehn MH, Tezel G. Glaucomatous tissue stress and the regulation of immune response through glial Toll-like receptor signaling. Invest Ophthalmol Vis Sci 2010;51:5697-5707.
150. Ayna G, Krysko DV, Kaczmarek A, Petrovski G, Vandenabeele P, Fesus L. ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages. PLoS One 2012;7:e40069.
151. Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, Fick L, et al. Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med 2010;182:774-783.
152. Pelegrin P. Targeting interleukin-1 signaling in chronic inflammation: Focus on P2X(7) receptor and Pannexin-1. Drug News Perspect. 2008;21:424-433.
153. de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci 2008;28:3404-3414.
154. Tezel G, Yang X, Yang J, Wax MB. Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells following optic nerve crush injury in mice. Brain Res 2004;996:202-212.
155. Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, et al. Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J Neurosci 2006;26:12633-12641.
156. Hyakkoku K, Hamanaka J, Tsuruma K, Shimazawa M, Tanaka H, Uematsu S, et al. Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia. Neuroscience 2010;171:258-267.
157. Dvoriantchikova G, Barakat DJ, Hernandez E, Shestopalov VI, Ivanov D. Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury. Mol Vis 2010;16: 1907-1912.
158. Barakat DJ, Dvoriantchikova G, Ivanov D, Shestopalov VI. Astroglial NF-kappaB mediates oxidative stress by regulation of NADPH oxidase in a model of retinal ischemia reperfusion injury. J Neurochem 2012;120: 586-597.
159. Murphy N, Cowley TR, Richardson JC, Virley D, Upton N, Walter D, Lynch MA. The Neuroprotective effect of a specific P2X(7) receptor antagonist derives from its ability to inhibit assembly of the NLRP3 inflammasome in glial cells. Brain Pathol 2011;22:295-306.
160. Tezel G, Wax MB. Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. J Neurosci 2000;20: 8693-8700.
161. Yang X, Luo C, Cai J, Powell DW, Yu D, Kuehn MH, et al. Neurodegenerative and inflammatory pathway components linked to TNF-alpha/TNFR1 signaling in the glaucomatous human retina. Invest Ophthalmol Vis Sci 2011;52:8442-8454.
162. Tezel G, Yang X, Luo C, Cai J, Powell DW. An astrocytespecific proteomic approach to inflammatory responses in experimental rat glaucoma. Invest Ophthalmol Vis Sci 2012;53:4220-4233.
163. Cabal-Hierro L, Lazo PS. Signal transduction by tumor necrosis factor receptors. Cell Signal 2012;24:1297-1305.
164. Blander JM, Sander LE. Beyond pattern recognition: Five immune checkpoints for scaling the microbial threat. Nat Rev Immunol 2012;12:215-225.
165. Ogura Y, Sutterwala FS, Flavell RA. The inflammasome: First line of the immune response to cell stress. Cell 2006; 126:659-662.
166. Creagh EM, O'Neill LA. TLRs, NLRs and RLRs: A trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol 2006;27:352-357.
167. Harari OA, Liao JK. NF-kappaB and innate immunity in ischemic stroke. Ann N Y Acad Sci 2010;1207:32-40.
168. Takahashi Y, Katai N, Murata T, Taniguchi SI, Hayashi T. Development of spontaneous optic neuropathy in NF-kappaBetap50-deficient mice: Requirement for NFkappaBetap50 in ganglion cell survival. Neuropathol Appl Neurobiol 2007;33:692-705.
169. Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell 2008;132:344-362.
170. Hanamsagar R, Hanke ML, Kielian T. Toll-like receptor (TLR) and inflammasome actions in the central nervous system. Trends Immunol 2012;33:333-342.
171. Tezel G. Immune regulation toward immunomodulation for neuroprotection in glaucoma. Curr Opin Pharmacol. 2013;13:23-31.
172. Baudouin SJ, Angibaud J, Loussouarn G, Bonnamain V, Matsuura A, Kinebuchi M, et al. The signaling adaptor protein CD3zeta is a negative regulator of dendrite development in young neurons. Mol Biol Cell 2008;19: 2444-2456.
173. Corriveau RA, Huh GS, Shatz CJ. Regulation of class I MHC gene expression in the developing and mature CNS by neural activity. Neuron 1998;21:505-520.
174. Huh GS, Boulanger LM, Du H, Riquelme PA, Brotz TM, Shatz CJ. Functional requirement for class I MHC in CNS development and plasticity. Science 2000;290: 2155-2159.
175. Ishii T, Hirota J, Mombaerts P. Combinatorial coexpression of neural and immune multigene families in mouse vomeronasal sensory neurons. Curr Biol 2003; 13:394-400.
176. Syken J, Shatz CJ. Expression of T cell receptor beta locus in central nervous system neurons. Proc Natl Acad Sci USA 2003;100:13048-13053.
177. Syken J, Grandpre T, Kanold PO, Shatz CJ. PirB restricts ocular-dominance plasticity in visual cortex. Science 2006; 313:1795-1800.
178. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, et al. Microglia sculpt postnatal neural circuits in an activity and complementdependent manner. Neuron 2012;74:691-705.
179. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. The classical complement cascade mediates CNS synapse elimination. Cell 2007;131:1164-1178.
180. Wu ZP, Washburn L, Bilousova TV, Boudzinskaia M, Escande-Beillard N, Querubin J, et al. Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair. J Neuroimmunol 2011;232:8-16.
181. Joseph MS, Bilousova T, Zdunowski S, Wu ZP, Middleton B, Boudzinskaia M, et al. Transgenic mice with enhanced neuronal major histocompatibility complex class I expression recover locomotor function better after spinal cord injury. J Neurosci Res 2011;89:365-372.
182. Boulanger LM, Huh GS, Shatz CJ. Neuronal plasticity and cellular immunity: Shared molecular mechanisms. Curr Opin Neurobiol 2001;11:568-578.
183. Fourgeaud L, Boulanger LM. Synapse remodeling, compliments of the complement system. Cell 2007;131: 1034-1036.
184. Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol 2009;27:591-619.
185. Kiefer F, Vogel WF, Arnold R. Signal transduction and costimulatory pathways. Transpl Immunol 2002;9:69-82.
186. Baniyash M. TCR zeta-chain downregulation: Curtailing an excessive inflammatory immune response. Nat Rev Immunol 2004;4:675-687.
187. Shatz CJ. MHC class I: An unexpected role in neuronal plasticity. Neuron 2009;64:40-45.
188. Bosco A, Crish SD, Steele MR, Romero CO, Inman DM, Horner PJ, et al. Early reduction of microglia activation by irradiation in a model of chronic glaucoma. Plos One 2012;7:e43602.
189. Bosco A, Inman DM, Steele MR, Wu G, Soto I, Marsh- Armstrong N, et al. Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 2008;49:1437-1446.
190. Bosco A, Steele MR, Vetter ML. Early microglia activation in a mouse model of chronic glaucoma. J Comp Neurol 2011;519:599-620.