Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2014, Article ID 320906, 11 pages
http://dx.doi.org/10.1155/2014/320906
Review Article

Purinergic Receptors in Ocular Inflammation

1Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Universidad Complutense de Madrid, C/Arcos de Jalón 118, 28037 Madrid, Spain
2Spanish Cooperative Thematic Research Network in Ocular Prevalent and Chronic Pathology (RETIC), Instituto de Salud Carlos III, Madrid, Spain
3Neurophysiology Lab, Department of Physiological Sciences I, Medical School, Universitat de Barcelona, Barcelona, Spain
4Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain
5Ocular Surface Group, Institute for Applied Ophthalmobiology (IOBA), University of Valladolid, Valladolid, Spain
6Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain

Received 25 April 2014; Accepted 17 June 2014; Published 14 July 2014

Academic Editor: Mireia Martín-Satué

Copyright © 2014 Ana Guzman-Aranguez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. V. Chesnokova and S. Melmed, “Minireview: neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gp130 signaling molecules,” Endocrinology, vol. 143, no. 5, pp. 1571–1574, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. C. Nathan, “Points of control in inflammation,” Nature, vol. 420, no. 6917, pp. 846–852, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. C. N. Serhan, “Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways,” Annual Review of Immunology, vol. 25, pp. 101–137, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Evereklioglu, “Ocular Behçet disease: current therapeutic approaches,” Current Opinion in Ophthalmology, vol. 22, no. 6, pp. 508–516, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. S. C. Maloney, K. D. Godeiro, A. N. Odashiro, and M. N. Burnier Jr., “Current and emerging concepts in the management of neovascular age-related macular degeneration,” Cardiovascular and Hematological Agents in Medicinal Chemistry, vol. 5, no. 2, pp. 147–154, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. I. Offiah and V. L. Calder, “Immune mechanisms in allergic eye diseases: what is new?” Current Opinion in Allergy and Clinical Immunology, vol. 9, no. 5, pp. 477–481, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. C. J. Chu, S. E. Barker, A. D. Dick, and R. R. Ali, “Gene therapy for noninfectious uveitis,” Ocular Immunology and Inflammation, vol. 20, no. 6, pp. 394–405, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Diebold, L. Contreras-Ruiz, I. Arranz-Valsero, and L. García-Posadas, “Drug delivery systems for ophthalmic administration of antiinflammatory agents,” Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, vol. 10, no. 3, pp. 203–214, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Y. Niederkorn and J. Stein-Streilein, “History and physiology of immune privilege,” Ocular Immunology and Inflammation, vol. 18, no. 1, pp. 19–23, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. A. W. Taylor, “Neuroimmunomodulation and immune privilege: the role of neuropeptides in ocular immunosuppression,” NeuroImmunoModulation, vol. 10, no. 4, pp. 189–198, 2002. View at Publisher · View at Google Scholar · View at Scopus
  11. T. Tervo, K. Tervo, and L. Eranko, “Ocular neuropeptides,” Medical Biology, vol. 60, no. 2, pp. 53–60, 1982. View at Google Scholar · View at Scopus
  12. D. A. Dartt, “Regulation of mucin and fluid secretion by conjunctival epithelial cells,” Progress in Retinal and Eye Research, vol. 21, no. 6, pp. 555–576, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. T. L. Kessler, H. J. Mercer, J. D. Zieske, D. M. McCarthy, and D. A. Dartt, “Stimulation of goblet cell mucous secretion by activation of nerves in rat conjunctiva,” Current Eye Research, vol. 14, no. 11, pp. 985–992, 1995. View at Publisher · View at Google Scholar · View at Scopus
  14. A. S. Bacon, P. Ahluwalia, A. Irani et al., “Tear and conjunctival changes during the allergen-induced early- and late-phase responses,” Journal of Allergy and Clinical Immunology, vol. 106, no. 5, pp. 948–954, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Ohbayashi, B. Manzouri, K. Morohoshi, K. Fukuda, and S. J. Ono, “The role of histamine in ocular allergy,” Advances in Experimental Medicine and Biology, vol. 709, pp. 43–52, 2010. View at Google Scholar · View at Scopus
  16. D. Hayashi, D. Li, C. Hayashi, M. Shatos, R. R. Hodges, and D. A. Dartt, “Role of histamine and its receptor subtypes in stimulation of conjunctival goblet cell secretion.,” Investigative ophthalmology & visual science, vol. 53, no. 6, pp. 2993–3003, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. R. G. Pourcho, “Neurotransmitters in the retina,” Current Eye Research, vol. 15, no. 7, pp. 797–803, 1996. View at Publisher · View at Google Scholar · View at Scopus
  18. C. J. Pycock, “Retinal neurotransmission,” Survey of Ophthalmology, vol. 29, no. 5, pp. 355–365, 1985. View at Publisher · View at Google Scholar · View at Scopus
  19. R. A. de Melo Reis, A. L. M. Ventura, C. S. Schitine, M. C. F. de Mello, and F. G. de Mello, “Müller glia as an active compartment modulating nervous activity in the vertebrate retina: neurotransmitters and trophic factors,” Neurochemical Research, vol. 33, no. 8, pp. 1466–1474, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. N. J. Sucher, S. A. Lipton, and E. B. Dreyer, “Molecular basis of glutamate toxicity in retinal ganglion cells,” Vision Research, vol. 37, no. 24, pp. 3483–3493, 1997. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Harada, C. Harada, K. Nakamura et al., “The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma,” Journal of Clinical Investigation, vol. 117, no. 7, pp. 1763–1770, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Bringmann, T. Pannicke, J. Grosche et al., “Müller cells in the healthy and diseased retina,” Progress in Retinal and Eye Research, vol. 25, no. 4, pp. 397–424, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. C. Martin, M. Leone, X. Viviand, M. Ayem, and R. Guieu, “High adenosine plasma concentration as a prognostic index for outcome in patients with septic shock,” Critical Care Medicine, vol. 28, no. 9, pp. 3198–3202, 2000. View at Publisher · View at Google Scholar · View at Scopus
  24. B. Sperlágh, M. Dóda, M. Baranyi, and G. Haskó, “Ischemic-like condition releases norepinephrine and purines from different sources in superfused rat spleen strips,” Journal of Neuroimmunology, vol. 111, no. 1-2, pp. 45–54, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. S. Gessi, S. Merighi, D. Fazzi, A. Stefanelli, K. Varani, and P. A. Borea, “Adenosine receptor targeting in health and disease,” Expert Opinion on Investigational Drugs, vol. 20, no. 12, pp. 1591–1609, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Haskó, J. Linden, B. Cronstein, and P. Pacher, “Adenosine receptors: therapeutic aspects for inflammatory and immune diseases,” Nature Reviews Drug Discovery, vol. 7, no. 9, pp. 759–770, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. B. B. Fredholm, A. P. Ijzerman, K. A. Jacobson, K. Klotz, and J. Linden, “International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors,” Pharmacological Reviews, vol. 53, no. 4, pp. 527–552, 2001. View at Google Scholar · View at Scopus
  28. R. J. Walkenbach and W.-T. Chao, “Adenosine regulation of cyclic AMP in corneal endothelium,” Journal of Ocular Pharmacology, vol. 1, no. 4, pp. 337–342, 1985. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Kvanta, S. Seregard, S. Sejersen, B. Kull, and B. B. Fredholm, “Localization of adenosine receptor messenger RNAs in the rat eye,” Experimental Eye Research, vol. 65, no. 5, pp. 595–602, 1997. View at Publisher · View at Google Scholar · View at Scopus
  30. C. H. Mitchell, K. Peterson-Yantorno, D. A. Carré et al., “A3 adenosine receptors regulate Cl- channels of nonpigmented ciliary epithelial cells,” The American Journal of Physiology—Cell Physiology, vol. 276, no. 3, part 1, pp. C659–C666, 1999. View at Google Scholar · View at Scopus
  31. M. Zhang, M. T. Budak, W. Lu et al., “Identification of the A3 adenosine receptor in rat retinal ganglion cells,” Molecular Vision, vol. 12, pp. 937–948, 2006. View at Google Scholar · View at Scopus
  32. C. Blazynski, “Characterization of adenosine A2 receptors in bovine retinal pigment epithelial membranes,” Experimental Eye Research, vol. 56, no. 5, pp. 595–599, 1993. View at Publisher · View at Google Scholar · View at Scopus
  33. E. A. Newman, “Calcium increases in retinal glial cells evoked by light-induced neuronal activity,” Journal of Neuroscience, vol. 25, no. 23, pp. 5502–5510, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. H. T. Lee, G. Gallos, S. H. Nasr, and C. W. Emala, “A1 adenosine receptor activation inhibits inflammation, necrosis, and apoptosis after renal ischemia-reperfusion injury in mice,” Journal of the American Society of Nephrology, vol. 15, no. 1, pp. 102–111, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Liao, S. Takashima, Y. Asano et al., “Activation of adenosine A1 receptor attenuates cardiac hypertrophy and prevents heart failure in murine left ventricular pressure-overload model,” Circulation Research, vol. 93, no. 8, pp. 759–766, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Kim, M. Kim, J. H. Song, and H. T. Lee, “Endogenous A1 adenosine receptors protect against hepatic ischemia reperfusion injury in mice,” Liver Transplantation, vol. 14, no. 6, pp. 845–854, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Tsutsui, J. Schnermann, F. Noorbakhsh et al., “A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis,” Journal of Neuroscience, vol. 24, no. 6, pp. 1521–1529, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. C. F. Neely, J. Jin, and I. M. Keith, “A1-adenosine receptor antagonists block endotoxin-induced lung injury,” The American Journal of Physiology, vol. 272, no. 2, pp. L353–L361, 1997. View at Google Scholar · View at Scopus
  39. D. S. Ponnoth, A. Nadeem, S. Tilley, and S. J. Mustafa, “Involvement of A1 adenosine receptors in altered vascular responses and inflammation in an allergic mouse model of asthma,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 299, no. 1, pp. H81–H87, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Perígolo-Vicente, K. Ritt, M. R. Pereira, P. M. M. Torres, R. Paes-de-Carvalho, and E. Giestal-de-Araujo, “IL-6 treatment increases the survival of retinal ganglion cells in vitro: The role of adenosine A1 receptor,” Biochemical and Biophysical Research Communications, vol. 430, no. 2, pp. 512–518, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. P. M. M. Torres and E. G. De Araujo, “Interleukin-6 increases the survival of retinal ganglion cells in vitro,” Journal of Neuroimmunology, vol. 117, no. 1-2, pp. 43–50, 2001. View at Publisher · View at Google Scholar · View at Scopus
  42. G. Haskó and P. Pacher, “A2A receptors in inflammation and injury: lessons learned from transgenic animals,” Journal of Leukocyte Biology, vol. 83, no. 3, pp. 447–455, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. A. S. Ibrahim, M. M. El-shishtawy, W. Zhang, R. B. Caldwell, and G. I. Liou, “A2A adenosine receptor (A2AAR) as a therapeutic target in diabetic retinopathy,” The American Journal of Pathology, vol. 178, no. 5, pp. 2136–2145, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. G. I. Liou, J. A. Auchampach, C. J. Hillard et al., “Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor,” Investigative Ophthalmology and Visual Science, vol. 49, no. 12, pp. 5526–5531, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. G. I. Liou, S. Ahmad, M. Naime, N. Fatteh, and A. S. Ibrahim, “Role of adenosine in diabetic retinopathy,” Journal of Ocular Biology, Diseases, and Informatics, vol. 4, no. 1-2, pp. 19–24, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. A. J. Barber, E. Lieth, S. A. Khin, D. A. Antonetti, A. G. Buchanan, and T. W. Gardner, “Neural apoptosis in the retina during experimental and human diabetes: early onset and effect of insulin,” Journal of Clinical Investigation, vol. 102, no. 4, pp. 783–791, 1998. View at Publisher · View at Google Scholar · View at Scopus
  47. A. B. El-Remessy, M. Al-Shabrawey, Y. Khalifa, N. Tsai, R. B. Caldwell, and G. I. Liou, “Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes,” American Journal of Pathology, vol. 168, no. 1, pp. 235–244, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. A. M. Joussen, V. Poulaki, M. L. Le et al., “A central role for inflammation in the pathogenesis of diabetic retinopathy,” The FASEB Journal, vol. 18, no. 12, pp. 1450–1452, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Al-Shabrawey, M. Rojas, T. Sanders et al., “Role of NADPH oxidase in retinal vascular inflammation,” Investigative Ophthalmology and Visual Science, vol. 49, no. 7, pp. 3239–3244, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. A. W. Stitt, T. Bhaduri, C. B. T. McMullen, T. A. Gardiner, and D. B. Archer, “Advanced glycation end products induce blood-retinal barrier dysfunction in normoglycemic rats,” Molecular Cell Biology Research Communications, vol. 3, no. 6, pp. 380–388, 2000. View at Publisher · View at Google Scholar · View at Scopus
  51. E. Rungger-Brändle, A. A. Dosso, and P. M. Leuenberger, “Glial reactivity, an early feature of diabetic retinopathy,” Investigative Ophthalmology and Visual Science, vol. 41, no. 7, pp. 1971–1980, 2000. View at Google Scholar · View at Scopus
  52. G. W. Kreutzberg, “Microglia: a sensor for pathological events in the CNS,” Trends in Neurosciences, vol. 19, no. 8, pp. 312–318, 1996. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Sayyah, M. Javad-Pour, and M. Ghazi-Khansari, “The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice: involvement of proinflammatory factors: nitric oxide and prostaglandins,” Neuroscience, vol. 122, no. 4, pp. 1073–1080, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. N. M. Elsherbiny, M. Naime, S. Ahmad et al., “Potential roles of adenosine deaminase-2 in diabetic retinopathy,” Biochemical and Biophysical Research Communications, vol. 436, no. 3, pp. 355–361, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Ahmad, N. Fatteh, N. M. El-Sherbiny et al., “Potential role of A2A adenosine receptor in traumatic optic neuropathy,” Journal of Neuroimmunology, vol. 264, no. 1-2, pp. 54–64, 2013. View at Publisher · View at Google Scholar
  56. D. J. Lee and A. W. Taylor, “Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice,” The Journal of Immunology, vol. 191, no. 8, pp. 4103–4111, 2013. View at Google Scholar
  57. I. Feoktistov and I. Biaggioni, “Role of adenosine A2B receptors in inflammation,” Advances in Pharmacology, vol. 61, pp. 115–144, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. V. L. Kolachala, M. Vijay-Kumar, G. Dalmasso et al., “A2B adenosine receptor gene deletion attenuates murine colitis,” Gastroenterology, vol. 135, no. 3, pp. 861–870, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Zhou, A. Mohsenin, E. Morschl et al., “Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor,” Journal of Immunology, vol. 182, no. 12, pp. 8037–8046, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Han, Y. Shao, Z. Lin et al., “Netrin-1 simultaneously suppresses corneal inflammation and neovascularization,” Investigative Ophthalmology & Visual Science, vol. 53, no. 3, pp. 1285–1295, 2012. View at Google Scholar
  61. P. Rosenberger, J. M. Schwab, V. Mirakaj et al., “Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia,” Nature Immunology, vol. 10, no. 2, pp. 195–202, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Ochaion, S. Bar-Yehuda, S. Cohen et al., “The anti-inflammatory target A3 adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease,” Cellular Immunology, vol. 258, no. 2, pp. 115–122, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. L. Madi, S. Cohen, A. Ochayin, S. Bar-Yehuda, F. Barer, and P. Fishman, “Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in rheumatoid arthritis: involvement of nuclear factor-κB in mediating receptor level,” Journal of Rheumatology, vol. 34, no. 1, pp. 20–26, 2007. View at Google Scholar · View at Scopus
  64. A. Ochaion, S. Bar-Yehuda, S. Cohn et al., “Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 adenosine receptor expression,” Arthritis Research and Therapy, vol. 8, no. 6, article R169, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. U. Schlotzer-Schrehardt, M. Zenkel, U. Decking et al., “Selective upregulation of the A3 adenosine receptor in eyes with pseudoexfoliation syndrome and glaucoma,” Investigative Ophthalmology & Visual Science, vol. 46, no. 6, pp. 2023–2034, 2005. View at Google Scholar
  66. P. Fishman, S. Bar-Yehuda, B. T. Liang, and K. A. Jacobson, “Pharmacological and therapeutic effects of A3 adenosine receptor agonists,” Drug Discovery Today, vol. 17, no. 7-8, pp. 359–366, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Bar-Yehuda, L. Rath-Wolfson, L. Del Valle et al., “Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment,” Arthritis and Rheumatism, vol. 60, no. 10, pp. 3061–3071, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. P. Fishman, S. Bar-Yehuda, L. Madi et al., “The PI3K-NF-κB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis,” Arthritis Research and Therapy, vol. 8, no. 1, article R33, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Mabley, F. Soriano, P. Pacher et al., “The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide, is protective in two murine models of colitis,” European Journal of Pharmacology, vol. 466, no. 3, pp. 323–329, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Rath-Wolfson, S. Bar-Yehuda, L. Madi et al., “IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis,” Clinical and Experimental Rheumatology, vol. 24, no. 4, pp. 400–406, 2006. View at Google Scholar · View at Scopus
  71. C. Szabó, G. S. Scott, L. Virág et al., “Suppression of macrophage inflammatory protein (MIP)-1α production and collagen-induced arthritis by adenosine receptor agonists,” British Journal of Pharmacology, vol. 125, no. 2, pp. 379–387, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Bar-Yehuda, D. Luger, A. Ochaion et al., “Inhibition of experimental auto-immune uveitis by the A3 adenosine receptor agonist CF101,” International Journal of Molecular Medicine, vol. 28, no. 5, pp. 727–731, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Acera, G. Rocha, E. Vecino, I. Lema, and J. A. Durán, “Inflammatory markers in the tears of patients with ocular surface disease,” Ophthalmic Research, vol. 40, no. 6, pp. 315–321, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. N. Boehm, A. I. Riechardt, M. Wiegand, N. Pfeiffer, and F. H. Grus, “Proinflammatory cytokine profiling of tears from dry eye patients by means of antibody microarrays,” Investigative Ophthalmology and Visual Science, vol. 52, no. 10, pp. 7725–7730, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Lam, L. Bleiden, C. S. de Paiva, W. Farley, M. E. Stern, and S. C. Pflugfelder, “Tear cytokine profiles in dysfunctional tear syndrome,” American Journal of Ophthalmology, vol. 147, no. 2, pp. 198–205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. W. Stevenson, S. K. Chauhan, and R. Dana, “Dry eye disease: an immune-mediated ocular surface disorder,” Archives of Ophthalmology, vol. 130, no. 1, pp. 90–100, 2012. View at Publisher · View at Google Scholar · View at Scopus
  77. I. Avni, H. J. Garzozi, I. S. Barequet et al., “Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial,” Ophthalmology, vol. 117, no. 7, pp. 1287–1293, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. A.-R. van Troostenburg, E. V. Clark, W. D. H. Carey et al., “Tolerability, pharmacokinetics and concentration-dependent hemodynamic effects of oral CF101, an A3 adenosine receptor agonist, in healthy young men,” International Journal of Clinical Pharmacology and Therapeutics, vol. 42, no. 10, pp. 534–542, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. J. N. Ashar, A. Mathur, and V. Sangwan, “CF101 for dry eye,” Ophthalmology, vol. 118, no. 5, pp. 1011–1012, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. B. Renga, M. Migliorati, A. Mencarelli, and S. Fiorucci, “Reciprocal regulation of the bile acid-activated receptor FXR and the interferon-γ-STAT-1 pathway in macrophages,” Biochimica et Biophysica Acta, vol. 1792, no. 6, pp. 564–573, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. S. G. Ward and P. Finan, “Isoform-specific phosphoinositide 3-kinase inhibitors as therapeutic agents,” Current Opinion in Pharmacology, vol. 3, no. 4, pp. 426–434, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. C. Belmonte, J. Garcia-Hirschfeld, and J. Gallar, “Neurobiology of ocular pain,” Progress in Retinal and Eye Research, vol. 16, no. 1, pp. 117–156, 1997. View at Publisher · View at Google Scholar · View at Scopus
  83. A. Reiner, H. J. Karten, P. D. R. Gamlin, and J. T. Erichsen, “Parasympathetic ocular control. Functional subdivisions and circuity of the avian nucleus of Edinger-Westphal,” Trends in Neurosciences, vol. 6, no. 4, pp. 140–145, 1983. View at Publisher · View at Google Scholar · View at Scopus
  84. M. P. M. Ten Tusscher, H. J. M. Beckers, G. F. J. M. Vrensen, and J. Klooster, “Peripheral neural circuits regulating IOP? A review of its anatomical backbone,” Documenta Ophthalmologica, vol. 87, no. 4, pp. 291–313, 1994. View at Publisher · View at Google Scholar · View at Scopus
  85. G. L. Ruskell, “The orbital branches of the pterygopalatine ganglion and their relationship with internal carotid nerve branches in primates,” Journal of Anatomy, vol. 106, no. 2, pp. 323–339, 1970. View at Google Scholar · View at Scopus
  86. V. Staikopoulos, B. J. Sessle, J. B. Furness, and E. A. Jennings, “Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons,” Neuroscience, vol. 144, no. 1, pp. 208–216, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. P. M. Dunn, Y. Zhong, and G. Burnstock, “P2X receptors in peripheral neurons,” Progress in Neurobiology, vol. 65, no. 2, pp. 107–134, 2001. View at Publisher · View at Google Scholar · View at Scopus
  88. H. Kuroda, Y. Shibukawa, M. Soya et al., “Expression of P2X1 and P2X4 receptors in rat trigeminal ganglion neurons,” NeuroReport, vol. 23, no. 13, pp. 752–756, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Z. Ruan and G. Burnstock, “Localisation of P2Y1 and P2Y4 receptors in dorsal root, nodose and trigeminal ganglia of the rat,” Histochemistry and Cell Biology, vol. 120, no. 5, pp. 415–426, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. J. Pintor, J. Sánchez-Nogueiro, M. Irazu, A. Mediero, T. Peláez, and A. Peral, “Immunolocalisation of P2Y receptors in the rat eye,” Purinergic Signalling, vol. 1, no. 1, pp. 83–90, 2004. View at Publisher · View at Google Scholar · View at Scopus
  91. D. J. Oswald, A. Lee, M. Trinidad et al., “Communication between corneal epithelial cells and trigeminal neurons is facilitated by purinergic (P2) and glutamatergic receptors,” PLoS ONE, vol. 7, no. 9, Article ID e44574, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. C. Mankus, C. Rich, M. Minns, and V. Trinkaus-Randall, “Corneal epithelium expresses a variant of P2X 7 receptor in health and disease,” PLoS ONE, vol. 6, no. 12, Article ID e28541, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. M. S. Cowlen, V. Z. Zhang, L. Warnock, C. F. Moyer, W. M. Peterson, and B. R. Yerxa, “Localization of ocular P2Y2 receptor gene expression by in situ hybridization,” Experimental Eye Research, vol. 77, no. 1, pp. 77–84, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. V. E. McGilligan, M. S. Gregory-Ksander, D. Li et al., “Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells,” PLoS ONE, vol. 8, no. 9, Article ID e74010, 2013. View at Publisher · View at Google Scholar
  95. C. Baldini, C. Rossi, F. Ferro et al., “The P2X7 receptor-inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome,” Journal of Internal Medicine, vol. 274, no. 5, pp. 480–489, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. N. A. Farahbakhsh and M. C. Cilluffo, “P2 purinergic receptor-coupled signaling in the rabbit ciliary body epithelium,” Investigative Ophthalmology and Visual Science, vol. 43, no. 7, pp. 2317–2325, 2002. View at Google Scholar · View at Scopus
  97. M. Shahidullah and W. S. Wilson, “Mobilisation of intracellular calcium by P2Y2 receptors in cultured, non-transformed bovine ciliary epithelial cells,” Current Eye Research, vol. 16, no. 10, pp. 1006–1016, 1997. View at Publisher · View at Google Scholar · View at Scopus
  98. C. H. Mitchell, D. A. Carré, A. M. Mcglinn, R. A. Stone, and M. M. Civan, “A release mechanism for stored ATP in ocular ciliary epithelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 12, pp. 7174–7178, 1998. View at Publisher · View at Google Scholar · View at Scopus
  99. E. Maul and M. Sears, “ATP is released into the rabbit eye by antidromic stimulation of the trigeminal nerve,” Investigative Ophthalmology and Visual Science, vol. 18, no. 3, pp. 256–262, 1979. View at Google Scholar · View at Scopus
  100. G. M. Mintenig, M. V. Sanchez-Vives, C. Martin, A. Gual, and C. Belmonte, “Sensory receptors in the anterior uvea of the cat's eye: an in vitro study,” Investigative Ophthalmology & Visual Science, vol. 36, no. 8, pp. 1615–1624, 1995. View at Google Scholar · View at Scopus
  101. D. Soto, N. Comes, E. Ferrer et al., “Modulation of aqueous humor outflow by ionic mechanisms involved in trabecular meshwork cell volume regulation,” Investigative Ophthalmology and Visual Science, vol. 45, no. 10, pp. 3650–3661, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Soto, J. Pintor, A. Peral, A. Gual, and X. Gasull, “Effects of dinucleoside polyphosphates on trabecular meshwork cells and aqueous humor outflow facility,” Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 3, pp. 1042–1051, 2005. View at Publisher · View at Google Scholar · View at Scopus
  103. C. E. Crosson, P. W. Yates, A. N. Bhat, Y. V. Mukhin, and S. Husain, “Evidence for multiple P2Y receptors in trabecular meshwork cells,” The Journal of Pharmacology and Experimental Therapeutics, vol. 309, no. 2, pp. 484–489, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. P. Conquet, B. Plazonnet, and J. C. le Douarec, “Arachidonic acid induced elevation of intraocular pressure and anti inflammatory agents,” Investigative Ophthalmology, vol. 14, no. 10, pp. 772–775, 1975. View at Google Scholar · View at Scopus
  105. J. G. Ladas, F. Yu, R. Loo et al., “Relationship between aqueous humor protein level and outflow facility in patients with uveitis,” Investigative Ophthalmology and Visual Science, vol. 42, no. 11, pp. 2584–2588, 2001. View at Google Scholar · View at Scopus
  106. R. S. Moorthy, A. Mermoud, G. Baerveldt, D. S. Minckler, P. P. Lee, and N. A. Rao, “Glaucoma associated with uveitis,” Survey of Ophthalmology, vol. 41, no. 5, pp. 361–394, 1997. View at Publisher · View at Google Scholar · View at Scopus