Aplicaciones de los cannabinoides en glaucoma

  1. S. Pinar-Sueiro
  2. R. Rodríguez-Puertas
  3. E. Vecino
Revista:
Archivos de la Sociedad Española de Oftalmologia

ISSN: 0365-6691

Año de publicación: 2011

Volumen: 86

Número: 1

Páginas: 16-23

Tipo: Artículo

DOI: 10.1016/J.OFTAL.2010.11.015 DIALNET GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Archivos de la Sociedad Española de Oftalmologia

Resumen

Introducción: El glaucoma es una neuropatía óptica lentamente progresiva que constituye una de las principales causas de ceguera legal en el mundo. Actualmente existe un limitado grupo de fármacos tópicos para su manejo médico, siendo necesario enfocar la investigación hacia nuevos horizontes terapéuticos como el potencialmente útil grupo de los agonistas de cannabinoides. Objetivo: Revisar a través de la literatura científica actual, los efectos beneficiosos a través de distintas vías de administración de los cannabinoides para la neuropatía óptica glaucomatosa. Desarrollo: Los receptores de cannabinoides han demostrado una amplia expresión en los tejidos oculares implicados en la regulación de la tensión ocular, así como en las capas internas de la retina. Mediante la activación de receptores específicos CB1, CB2 y vías aún no bien conocidas, los agonistas de cannabinoides han demostrado un claro efecto hipotensor ocular, así como un probado efecto neuroprotector sobre las células ganglionares de la retina en estudios experimentales. Conclusiones: Algunos cannabinoides (WIN 55212-2, anandamida) han demostrado a nivel experimental actuar como «fármacos ideales» en el manejo del glaucoma, al presentar buena tolerancia tras su aplicación tópica, reducir de forma eficaz la presión intraocular, y presentar un probado carácter neuroprotector sobre las células ganglionares de la retina. Se deben realizar más estudios sobre su seguridad y ensayos clínicos para poder examinar la utilidad de estos fármacos en el tratamiento del glaucoma en nuestra clínica diaria.

Referencias bibliográficas

  • Lastres-Becker, I, Molina-Holgado, F, Ramos, JA, Mechoulam, R, Fernández-Ruiz, J. (2005). Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson´s disease. Neurobiol Dis.. 19. 96-107
  • Ramírez, BG, Blázquez, C, Gómez, DP, Guzmán, M, De Ceballos, ML. (2005). Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci.. 25. 1904
  • Panikashvili, D, Simeonidou, C, Ben-Shabat, S, Hanus, L, Breuer, A, Mechoulam, R. (2001). An endogenous cannabinoid (2AG) is neuroprotective after brain injury. Nature. 413. 527
  • Amantea, D, Spagnuolo, P, Bari, M, Fezza, F, Mazzei, C, Tassorelli, C. (2007). Modulation of the endocannabinoid system by focal brain ischemia in the rat is involved in neuroprotection afforded by 17beta-estradiol. FEBS J.. 274. 4464
  • Centonze, D, Rossi, S, Finazzi-Agró, A, Benardi, G, Maccarrone, M. (2007). The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis. Int Rev Neurobiol.. 82. 171
  • Macarrone, M, Battista, N, Centonze, D. (2007). The endocannabinoid pathway in Huntington´s disease: a comparison with other neurodegenerative diseases. Prog Neurobiol.. 81. 349
  • Hepler, RS, Frank, IM, Petrus, R. (1976). The Pharmacology of marihuana. Raven Press. New York^eNY NY.
  • García-Valenzuela, E, Shareef, S, Walsh, J, Sharma, SC. (1995). Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res.. 61. 33-44
  • Dong, CJ, Guo, Y, Agey, P, Wheeler, L, Hare, WA. (2008). Alpha2 adrenergic modulation of NMDA receptor function as a major mechanism of RGC protection in experimental glaucoma and retinal excitotoxicity. Invest Ophthalmol Vis Sci.. 49. 4515
  • Dewey, WL. (1986). Cannabinoid pharmacology. Pharmacol Rev.. 38. 151
  • Gaoni, Y, Mechoulam, R. (1964). Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc.. 86. 1646
  • Turner, CE, El Sohy, MA, Boeren, EG. (1989). Constituent of cannabis sativa L: A review of the natural constituent. Nat Procl.. 43. 169-234
  • Freud, TR, Katona, I, Piomelli, D. (2003). Role of endogenous cannabinoids in synaptic signaling. Physiol Rev.. 83. 1017
  • Matsuda, S, Kanemitsu, N, Nakamura, A, Mimura, Y, Ueda, N, Kurahashi, Y. (1997). Metabolism of anandamide, an endogenous cannabinoid receptor ligand, in porcine ocular tissues. Exp Eye Res.. 64. 707
  • Bisogno, T, Delton-Vandenbroucke, I, Milone, A, Lagarde, M, Di Marzo, V. (1999). Biosynthesis and inactivation of N-arachidonoylethanolamine (anandamide) and N-docosahexaenoylethanolamine in bovine retina. Arch Biochem Biophys.. 370. 300
  • Glaser, ST, Deutsch, DG, Studholme, KM, Zimov, S, Yazulla, S. (2005). Endocannabinoids in the intact retina: 3H-anandamide uptake, fatty acid amide hydrolase immunoreactivity and hydrolysis of anandamide. Vis Neursoci.. 22. 693-705
  • Chen, J, Matias, I, Dinh, T, Lu, T, Venezia, S, Nieves, A. (2005). Finding of endocannabinoids in human eye tissues: implications for glaucoma. Biochem Biophys Res Commun.. 330. 1062
  • He, F, Song, ZH. (2007). Molecular and celular changes induced by the activation of CB2 cannabinoid receptors in trabecular meshwork cells. Mol Vis.. 13. 1348
  • Chien, FY, Wang, RF, Mittag, TW. (2003). Effects of WIN-55212-2, a cannabinoid receptor agonist, on aqueous humor dynamic in monkeys. Arch Ophthalmol.. 126. 498-505
  • Struik, ML, Yazulla, S, Kamermans, M. (2006). Cannabinoid agonist WIN 55212-2 speeds up the cone response to light offset in goldfish retina. Vis Neurosci.. 23. 285
  • Van der Stelt, M, Veldhuis, WB, van Haaften, GW, Fezza, F, Bisogno, T, Bar, PR. (2001). Exogenous anandamide protects rat brain against acute neuronal injury in vivo. J Neurosci.. 278. 157
  • Matsuda, LA, Lolait, SJ, Brownstein, MJ, Young, AC, Bonner, TI. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 346. 56156
  • Munro, S, Thomas, KL, Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature. 365. 61
  • Breivogel, CS, Griffin, G, Di Marzo, V, Martin, BR. (2001). Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol.. 60. 155
  • Porcella, A, Casellas, P, Gessa, GL, Pani, L. (1998). Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana. Brain Res Mol Brain Res.. 58. 240
  • Straiker, AJ, Maguire, G, Mackie, K, Lindsey, J. (1999). Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol Vis Sci.. 40. 2442
  • Yazulla, S, Studholme, KM, McIntosh, HH, Deutsch, DG. (1999). Immunocytochemical localization of cannabinoid CB1 receptor and fatty acidamide hydrolase in rat retina. J Comp Neurol.. 415. 80-90
  • Romano, MR, Lograno, MD. (2006). Cannabinoid agonists induce relaxation in the bovine ophthalmic artery for CB1 receptors, nitric oxide and potassium channels. Br J Pharmacol.. 147. 917
  • Green, K. (1998). Marijuana smoking vs cannabinoids for glaucoma therapy. Arch Ophthalmol.. 116. 1433
  • Hepler, RS, Petrus, RJ. (1976). The therapeutic potential of marihuana. Plenum Publishing. New York.
  • Cooler, P, Gregg, JM. (1976). The therapeutic potential of marihuana. Plenum Publishing. New York.
  • Tomida, I, Azuara-Blanco, A, House, H, Flint, M, Pertwee, RG, Robson, PJ. (2006). Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 15. 349
  • Naveh, N, Weissman, C, Muchtar, S, Benita, S, Mechoulam, R. (2000). A submicron emulsion of HU-211, a synthetic cannabinoid, reduces intraocular pressure in rabbits. Graefes Arch Exp Ophthalmol.. 238. 334
  • Porcella, A, Maxia, C, Gessa, GL, Pani, L. (2001). The synthetic cannabinoid WIN 55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur J Neurosci.. 13. 409
  • Stamer, WD, Golightly, SF, Hosohata, Y, Ryan, EP, Porter, AC, Varga, E. (2001). Cannabinoid CB1 receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues. Eur J Pharmacol.. 431. 277
  • Colasanti, BK. (1990). A comparison of the ocular and central effects of delta-9-tetrahydrocannabinol and cannabigerol. J Ocular Pharmacol.. 6. 259
  • Njie, YF, Kumar, A, Qiao, Z, Zhong, L, Song, Z-H. (2006). Noladin ether acts on trabecular meshwork cannabinoid (CB1) receptor to enhance aqueous humor outflow facility. Invest Ophthalmol Vis Sci.. 47. 1999-2005
  • ltmanns, MH, Samudre, SS, Castillo, IG, Hosseini, A, Lichtman, AH, Allen, RC. (2008). Topical WIN 55212-2 alleviates intraocular hypertension in rats through a CB1 receptor-mediated mechanism of action. J Ocul Pharmacol Ther.. 24. 104
  • Devane, WA, Hanus, L, Breuer, A, Pertwee, RG, Stevenson, LA, Griffin, G. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 258. 1946
  • Beilin, M, Neumann, R, Belkin, M, Green, K, Bar-llan, A. (2000). Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid. J Ocul Pharmacol Ther.. 16. 217
  • Howlett, AC, Bidaut-Russell, M, Devane, WA, Melvin, LS, Johnson, MR, Herkenham, M. (1990). The cannabinoid receptor: biochemical, anatomical and behavioral characterization. Trends Neurosci.. 13. 40
  • Galve-Roperh, I, Aguado, T, Palazuelos, Y, Guzmán, M. (2008). Mechanisms of control of neuron survival by the endocannabinoid system. Curr Pharm Des.. 14. 2279
  • Marsicano, G, Goodenough, S, Monory, K, Hermann, H, Eder, M, Cannich, A. (2003). CB1 cannabinoid receptors on-demanmd defense against excitotoxicity. Science. 302. 84
  • Khaspekov, LG, Brenz, MS, Frumkina, LE, Hermann, H, Marsicano, G, Lutz, B. (2004). Involvement of brain-derived neurotrophic factor in cannabinoid-dependent protection against excitotoxicity. Eur J Neurosci.. 19. 1691
  • Molina-Holgado, E, Vela, JM, Arévalo-Martín, A, Almazán, G, Molina-Holgado, F, Borrell, J. (2002). Cannabinoids promote oligodendrocyte progenitor survival: Involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci.. 22. 9742
  • Eljaschewitsch, E, Witting, A, Mawrin, C, Lee, T, Schmidt, PM, Wolf, S. (2006). The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron. 49. 67-79
  • Veldhuis, WB, van der Stelt, M, Wadman, MW, van Zadelhoff, G, Maccarrone, M, Fezza, F. (2003). Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxcity in the rat: role of vanilloid receptors and lipoxygenases. J Neurosci.. 23. 4127
  • Liu, J, Wang, L, Harvey -White, J, Osei-Hyiaman, D, Razdam, R, Song, G. (2006). A biosynthetic pathway for anandamide. Proc Natl Acad Sci USA. 103. 13345
  • Vink, R, Nimmo, AJ. (2009). Multifunctional drugs for head injury. Neurotherapeutics. 6. 28-42
  • Nucci, C, Tartaglione, R, Rombola, L, Morrone, LA, Fazzi, E, Bagetta, G. (2005). Neurochemical evidence to implicate elevated glutamate in the mechanisms of high intraocular pressure (IOP)-induced retinal ganglion cell death in rat. Neurotoxicology. 26. 935
  • Honkanen, RA, Baruah, S, Zimmerman, MB, Khanna, CL, Weaver, YK, Narkiewicz, J. (2003). Vitreous amino acid concentrations in patients with glaucoma undergoing vitrectomy. Arch Ophthalmol.. 121. 183
  • El-Remessy, AB, Khalil, IE, Matragoon, S, Abou-Mohamed, G, Tsai, N-J, Roon, P. (2003). Neuroprotective effect of (-)D 9-tetrahydrocannabinol and cannabidiol in N-Methyl-D-Aspartate-induced retinal neurotoxicity. Am J Pathol.. 163. 1977-2008
  • Sisk, DR, Kuwabara, T. (1985). Histologic changes in the inner retina of albino rats following intravitreal injection of monosodium L-glutamate. Graefes Arch Clin Exp Ophthalmol.. 223. 250
  • Samy, CN, Lui, CJ, Kaiser, PK, Lipton, SA, Dreyer, EB. (1994). Toxicity of chronic glutamate administration to retina. Invest Ophthalmol Vis Sci.. 35. 497
  • Glovinsky, Y, Quigley, HA, Pease, ME. (1993). Foveal ganglion cell loss is size dependent in experimental glaucoma. Invest Ophthalmol Vis Sci.. 34. 395-400
  • Marsicano, G, Moosmann, B, Hermann, H, Lutz, B, Behlt, C. (2002). Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J Neurochem.. 80. 448
  • Twitchell, W, Brown, S, Mackie, K. (1997). Cannabinoids inhibit N- and P/Q-type calcium channel in cultured rat hyppocampal neurons. J Neurophysiol.. 78. 43-50
  • Bisogno, T, Haus, L, De Petrocellis, L, Tchilibon, S, Ponde, DE, Brandi, I. (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol.. 134. 845
  • Sugiura, T, Kodaka, T, Nakane, S, Kishimoto, S, Kondo, S, Waku, K. (1998). Detection of an endogenous cannabimimetic molecule, 2-arachidonoylglycerol, and cannabinoid CB1 receptor mRNA in human vascular cells: is 2-arachidonoylglycerol a possible vasomodulator?. J Biochem Biophys Res Commun.. 243. 838
  • Quigley, HA, Hohman, RM, Addicks, EM, Green, WR. (1984). Blood vessels of the glaucomatous optic disk in experimental primate and human eyes. Invest Ophthalmol Vis Sci.. 25. 918
  • Hafez, AS, Bizzarro, RLG, Lesk, MR. (2003). Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma patients: Ocular hypertension and normal subjects. Am J Ophthalmol.. 136. 1022
  • Mukhopadhyay, S, Chapnick, BM, Howlett, AC. (2002). Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent. Am J Physiol.. 282. 2046
  • Merritt, JC. (1982). Glaucoma, hypertension and marijuana. J Natl Med Assoc.. 74. 715
  • Plange, N, Arend, KO, Kaup, M, Doehmen, B, Adams, H, Hendricks, S. (2007). Dronabinol and retinal hemodynamics in humans. Am J Ophthalmol.. 143. 173
  • Green, K, Wynn, H, Padgett, D. (1978). Effects of delta-9-tetrahydrocannabinol on ocular blood flow and aqueous humor formation. Exp Eye Res.. 26. 65
  • Rosenkrantz, H, Fleischman, RW. (1979). Marihuana: Biological effects. Pergamon Press. Elmsford^eNY NY.
  • Pertwee, RG. (2000). Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development. Exp Opin Invest Drugs. 9. 1553
  • Martín, BR. (1986). Cellular effects of cannabinoids. Pharmacolog Rev.. 38. 45-74
  • Hodges, LC, Reggio, PH, Green, K. (1997). Evidence against cannabinoid receptor involvement in intraocular pressure effects of cannabinoids in rabbits. Ophthalmic Res.. 29. 1-5
  • Colasanti, BK, Craig, CR, Allora, DR. (1984). Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol. Exp Eye Res.. 39. 251
  • Hosseini, A, Lattanzio, FA, Williams, PB, Tibbs, D, Samudre, SS, Allen, RC. (2006). Chronic topical administration of WIN-55212-2 maintains a reduction in IOP in a rat glaucoma model without adverse effects. Exp Eye Res.. 82. 753
  • Pate, DW, Järvinen, K, Urtti, A, Mahadevan, V, Järvienen, T. (1988). Effect of the CB1 receptor antagonist, SR141716A, on cannabinoid-induced ocular hypotension in normotensive rabbits. Life Sci.. 63. 2181
  • Pate, DW, Järvinen, K, Urtti, A, Jarho, P, Fich, M, Mahadevan, V. (1996). Effects of topical anandamide on intraocular pressure in normotensive rabbits. Life Sci.. 58. 1849
  • Green, K, Roth, M. (1982). Ocular effects of topical administration of delta 9-tetrahydrocannabinoid in man. Arch Ophthalmol.. 100. 265
  • Yazulla, S. (2008). Endocannabinoids in the retina: from marihuana to neuroprotection. Prog Retin Eye Res.. 27. 501
  • Pinar-Sueiro, S. (2009). Role of cannabinoids in glaucoma. Arch Soc Esp Oftalmol.. 84. 487
  • Nucci, C, Bari, M, Spanò, A, Corasaniti, M, Bagetta, G, Maccarrone, M. (2008). Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure to neurprotection. Prog Brain Res.. 173. 451
  • Candrall, J, Matragoon, S, Khalifa, YM, Borlogan, C, Tsai, NT, Caldwell, RB. (2007). Neuroprotective and intraocular pressure-lowering effects of (-)Delta-9-tetrahydrocannibol in a rat model of glaucoma. Ophthalmic Res.. 39. 69-75