##article.abstract##
<strong>Introducción:</strong> el glaucoma es una de las principales causas de ceguera legal en el mundo; es la enfermedad neurodegenerativa retiniana más prevalente. Los tratamientos estándar se limitan a reducir la presión intraocular, por lo que se requieren nuevas alternativas terapéuticas. Los cannabinoides, además de reducir la presión intraocular, muestran actividad neuroprotectora contra la serie de vías hostiles que desencadena la apoptosis ganglionar. <strong>Objetivo:</strong> describir la aplicación del sistema cannabinoide en la fisiopatología del glaucoma. <strong>Métodos:</strong> el acceso de la información se realizó mediante las bases de datos científicas como Medline, Science Direct y Pubmed, con un intervalo de tiempo entre 1990 y 2018. Para clasificar la calidad de la información se hizo uso de una matriz sistemática conocida CEBM (Evidence-Based Medicine). <strong>Resultados:</strong> se encontró que a través de los receptores cannabinoides CB1 acoplados a proteínas G, se repercute de manera directa sobre la estimulación de receptores α1 y α2, lo que disminuye la producción y aumenta el drenaje del humor acuoso a través de la malla trabecular y la vía uveoescleral. Además inhibe receptores de glutamato de N-metil-D-aspartato que inducen la liberación masiva de glutamato, la producción de la enzima óxido nítrico sintasa y la endotelina 1. Conclusión: el tratamiento con cannabis puede considerarse como un método novedoso para controlar el glaucoma, ya que presenta buena tolerancia tras su aplicación tópica en ensayos clínicos; también ejerce control en las reacciones dañinas de los radicales libres, estimula la microcirculación neuronal y regula la hipoxia retiniana##submission.citations##
Pinar S, Rodríguez P, Vecino E. Aplicaciones de los cannabinoides en glaucoma. Arch Soc Esp Oftalmol. 2011;86(1):16-23
Nucci C, Russo R, Martucci A, Giannini C, Garaci F, Floris R, et al. New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system. Eur J Pharmacol. 2016;787:119-26
Bromfield S, McGwin G. Use of complementary and alternative medicine for eye-related diseases and conditions. Curr Eye Res. 2013;38(12):1283-7
Nuutimen T. Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus. Eur J Med Chem. 2018;157:198-228
American Academy of Ophthalmology. Glaucoma. San Francisco: Elsevier; 2010
Buettner H. Guía de la Clínica Mayo sobre visión y salud ocular. Madrid: Trillas; 2005. p. 83-100
Porcella A, Casellas P, Gessa GL, Pani L. Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana. Brain Res Mol Brain Res. 1998;58(1):240-5
Manterola C, Asenjo C, Otzen T. Jerarquización de la evidencia: Niveles de evidencia y grados de recomendación de uso actual. Rev Chil Infectol. 2014;31(6):705-18
Stephen A. Therapeutic potential of cannabis-related drugs. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64(4):157-67
Jackson S, Lara T, Pryce G, Baker D. Cannabinoids and neuroprotection in CNS inflammatory disease. J Neurol Sci. 2005;233(1):21-5
Nguyen D, Hee R, Chung K. Structural mechanism of G protein activation by G protein-coupled receptor. Eur J Pharmacol. 2015;763(15):214-22
Ronald Z, Duman E, Nestler J. Chapter 21-G proteins. En: Scott B, Siegel G, Bazan N, et al., editores. Basic neurochemistry. 8a. ed. Chicago: Academic Press; 2012. p. 411-22
Garzón J. Principios básicos de la farmacología ocular. En: Triana G, Montaño S, Montaña A. Farmacoterapia ocular. Bogotá; Unisalle; 2011. p. 15-32
Jaramillo P, Pradilla L, Bracho Y, Silva F. The endocannabinoid system and its relation with central obesity and metabolic syndrome: therapeutic implications. Rev Col Cardio. 2005;12(3):113-21
Despina K, Panagiota C, Kounenidakis M, Foteini K, Thermos K. Endogenous and synthetic cannabinoids as therapeutics in retinal disease. Neural Plast. 2016;(2016):8373020. http://dx.doi.org/10.1155/2016/8373020
Stumpff F, Boxberger M, Krauss A, Rosenthal R, Meissner S, Choritz L, et al. Stimulation of cannabinoid (CB1) and prostanoid (EP2) receptors opens BKCa channels and relaxes ocular trabecular meshwork. Exp Eye Res. 2005;80(5):697-708
Yoanner P, Ibraín D, Germán A, Fumero F, Darlen R, Sánchez L. Fisiología trabecular y glaucoma de ángulo abierto. Rev Cubana Oftalmol. 2012;25(supl. 1):458-66
Maurya N, Velmurugan BK. Therapeutic applications of cannabinoids. Chem Biol Interact. 2018;293:77-88
Snider N, Walker V, Hollenberg P. Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications. Pharmacol Rev. 2010;62(1):136-54
Baggelaar M, Maccarrone M, van der Stelt M. 2-arachidonoylglycerol: a signaling lipid with manifold actions in the brain. Prog Lipid Res. 2018;71:1-17
Pribasnig A, Mrak I, Grabner GF, Taschler U, Knittelfelder O, Scherz B, et al. / hydrolase domain-containing 6 (ABHD6) degrades the late endosomal/lysosomal lipid bis(monoacylglycero)phosphate. J Biol Chem. 2015;290(50):29869-81
Panahi Y, Manayi A, Marjan N, Vazirian M. The arguments for and against cannabinoids application in glaucomatous retinopathy. Biomed Pharmacother. 2017;86:620-7
Cairns E, Baldbridge W, Hohmann A. The endocannabinoid system as a therapeutic target in glaucoma. CNS Neurol Disord Drug Targets. 2016;8(6):403-21
Alhouayek M, Muccioli G. COX-2-derived endocannabinoid metabolites as novel inflammatory mediators. Trends Pharmacol Sci. 2014;35(6):284-92
Sagar D, Gaw AG, Okine BN, Woodhams SG, Wong A, Kendall DA, Chapman V. Dynamic regulation of the endocannabinoid system: implications for analgesia. Mol Pain. 2009;5:59
Vohra R, Tsai J, Kolko M. The role of inflammation in the pathogenesis of glaucoma. Surv Ophthalmol. 2013;58(4):311-20
Jarvis S, Rassmussen S, Winters B. Role of the endocannabinoid system and medical cannabis. J Nurse Pract. 2017;13(8):525-31
Porcella A, Maxia C, Gessa GL, Pani L. The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur J Neurosci. 2001;13(2):409-12
Chien F, Wang R, Mittag T, Podos S. Effect of WIN 55212-2, a cannabinoidreceptor agonist, on aqueous humor dynamics in monkeys. Arch Ophthalmol. 2003;121(1):87-90
Song Z, Slowey C. Involvement of cannabinoid receptors in the intraocular pressure-lowering effects of WIN55212-2. J Pharmacol Exp Ther. 2000;292(1):136-9
Colasanti B. A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol. J Ocul Pharmacol. 1990;6(4):259-69
Hosseini A, Lattanzio FA, Williams PB, Tibbs D, Samudre SS, Allen RC. Chronic topical administration of WIN-55-212-2 maintains a reduction in IOP in a rat glaucoma model without adverse effects. Exp Eye Res. 2006;82(5):753-9
Chen J, Matias I, Dinh T, Lu T, Venezia S, Nieves A, Woodward DF, Di Marzo V. Finding of endocannabinoids in human eye tissues: implications for glaucoma. Biochem Biophys Res Commun. 2005;330(4):1062-7
Stamer D, Golightly SF, Hosohata Y, Ryan EP, Porter AC, Varga E, et al. Cannabinoid CB(1) receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues. Eur J Pharmacol. 2001;431(3):277-86
Lu Q, Straiker A, Maguire G. Expression of CB2 cannabinoid receptor mRNA in adult rat retina. Vis Neurosci. 2000;17(1):91-5
Sánchez AJ, García-Merino A. Neuroprotective agents: cannabinoids. Clin Immunol. 2012;142(1):57-67
Kokona D, Georgiou P, Kounenidakis M, Kiagiadaki F, Thermos K. Endogenous and synthetic cannabinoids as therapeutics in retinal disease. Neural Plast. 2016;(2016):8373020
Baltmr A, Duggan J, Shereen N, Salt M, Cordeiro F. Neuroprotection in glaucoma Is there a future role? Exp Eye Res. 2010;91(5):554-66
Liberatore F, Bucci D, Mascio G, Madonna M, Di Pietro P, Beneventano M, et al. Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration. Neuroscience. 2017;363:142-9
Lawlor M, Danesh-Meyer H, Levin LA, Davagnanam I, De Vita E, Plant GT. Glaucoma and the brain: trans-synaptic degeneration, structural change, and implications for neuroprotection. Surv Ophthalmol. 2018;63(3):296-306
Nucci C, Bari M, Spano A, Corasantini M, Baget G, Maccarrone M, Morrone LA. Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection. Prog Brain Res. 2008;173:451-64
Pate W, Laine K, Jarvinen T. Cannabinoids in the treatment of glaucoma. Pharmacol Ther. 2002;95(2):203-20
Zhang Q, Wang W, Alatantuya, Dongmei, Lu ZJ, Li LL, Zhang TZ. Down-regulated miR-187 promotes oxidative stress-induced retinal cell apoptosis through P2X7 receptor. Int J Biol Macromol. 2018;120(1):801-10
Chrysostomou V, Rezania F, Trounce IA, Crowston G. Oxidative stress and mitochondrial dysfunction in glaucoma. Curr Opin Pharmacol. 2013;13(1):12-5
Yazulla S. Endocannabinoids in the retina: from marijuana to neuroprotection. Prog Retin Eye Res. 2008;27(5):501-26
Glenna L, Hee G, Jung J, Waataja S, Thayer A. Δ9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. Brain Res. 2007;1128(1):61-9
Tomida I, Pertwee G, Azuara B. Cannabinoids and glaucoma. Br J Ophthalmol. 2004;88(5):708-13
Hingorani T, Gul W, Elsohly M, Repka A, Majumdar S. Effect of ion pairing on in vitro transcorneal permeability of a 9-tetrahydrocannabinol prodrug: potential. J Pharm Sci. 2012;101(2):616-26
Kearse C, Green K. Effect of vehicle upon in vitro transcorneal permeability and intracorneal content of Delta9-tetrahydrocannabinol. Curr Eye Res. 2000;20(6):496-501
Green K, Kearse C, McIntyre L. Interaction between delta-9-tetrahydrocannabinol and indomethacin. Ophthalmic Res. 2001;33(4):217-20
