Turning Down the Thermostat: Modulating the Endocannabinoid System in Ocular Inflammation and Pain.
The endocannabinoid system (ECS) has emerged as an important regulator of both physiological and pathological processes. Notably, this endogenous system plays a key role in the modulation of pain and inflammation in a number of tissues. The components of the ECS, including endocannabinoids, their cognate enzymes and cannabinoid receptors, are localized in the eye, and evidence indicates that ECS modulation plays a role in ocular disease states. Of these diseases, ocular inflammation presents a significant medical problem, given that current clinical treatments can be ineffective or are associated with intolerable side-effects. Furthermore, a prominent comorbidity of ocular inflammation is pain, including neuropathic pain, for which therapeutic options remain limited. Recent evidence supports the use of drugs targeting the ECS for the treatment of ocular inflammation and pain in animal models; however, the potential for therapeutic use of cannabinoid drugs in the eye has not been thoroughly investigated at this time. This review will highlight evidence from experimental studies identifying components of the ocular ECS and discuss the functional role of the ECS during different ocular inflammatory disease states, including uveitis and corneal keratitis. Candidate ECS targeted therapies will be discussed, drawing on experimental results obtained from both ocular and non-ocular tissue(s), together with their potential application for the treatment of ocular inflammation and pain.
Department of Pharmacology, Dalhousie University, Halifax NS, Canada.
James T
JT
Toguri
Department of Pharmacology, Dalhousie University, Halifax NS, Canada.
Meggie
M
Caldwell
Department of Pharmacology, Dalhousie University, HalifaxNS, Canada; Department of Ophthalmology and Visual Sciences, Dalhousie University, HalifaxNS, Canada; Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, HalifaxNS, Canada.
Melanie E M
ME
Kelly
cannabinoids; corneal inflammation; eye; inflammation; ocular cannabinoids; ocular inflammation; ocular pain; pain
J Leukoc Biol. 2007 Jun;81(6):1345-51
17405851
Eur J Pharmacol. 2001 Nov 23;431(3):277-86
11730719
Acta Ophthalmol. 2010 May;88(3):292-9
19900207
Neural Plast. 2016;2016:9247057
26839718
Br J Ophthalmol. 2004 May;88(5):708-13
15090428
Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2442-8
10476817
Acta Anaesthesiol Taiwan. 2013 Dec;51(4):161-70
24529672
Arch Soc Esp Oftalmol. 2011 Jan;86(1):16-23
21414525
Exp Eye Res. 2010 Apr;90(4):478-92
20036654
Invest Ophthalmol Vis Sci. 2002 Mar;43(3):639-46
11867578
Prog Retin Eye Res. 2013 Mar;33:10-27
23108335
Am J Ophthalmol. 2005 Sep;140(3):509-16
16196117
Semin Ophthalmol. 2016;31(1-2):59-70
26959131
Pain. 2010 Nov;151(2):337-344
20696525
J Leukoc Biol. 2007 Sep;82(3):532-41
17537989
Curr Ophthalmol Rep. 2015;3(2):111-121
26000205
Arch Ophthalmol. 2010 Jun;128(6):731-7
20547951
J Clin Invest. 2010 Sep;120(9):3073-83
20811163
J Pharmacol Exp Ther. 2010 May;333(2):445-53
20164299
Exp Eye Res. 1997 Jun;64(6):905-12
9301471
Invest Ophthalmol Vis Sci. 2007 Jul;48(7):2997-3004
17591864
Prog Retin Eye Res. 2008 Sep;27(5):501-26
18725316
Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3649-58
18316698
Can J Ophthalmol. 2010 Aug;45(4):324-6
20676153
Immunol Cell Biol. 1998 Dec;76(6):497-512
9893027
Nat Rev Neurol. 2013 Jan;9(1):44-53
23165340
Cell Signal. 2013 Feb;25(2):501-11
23142606
Eye (Lond). 1997;11 ( Pt 2):183-93
9349410
Brain Res Mol Brain Res. 1999 Apr 6;67(1):148-57
10101241
Pharmacol Ther. 2002 Aug;95(2):203-20
12182967
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14565-70
10588745
PLoS One. 2013 Apr 16;8(4):e61799
23613940
Clin Hemorheol Microcirc. 2015;61(2):237-49
26410875
Eye (Lond). 2015 Mar;29(3):301-12
25376119
Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3234-50
8045716
J Ocul Pharmacol Ther. 2011 Dec;27(6):545-52
21848425
J Leukoc Biol. 2008 Sep;84(3):721-9
18577714
Eye (Lond). 2003 Nov;17(8):949-56
14631402
Cornea. 2011 Apr;30(4):379-87
21045640
Synapse. 2011 May;65(5):388-92
20803619
J Leukoc Biol. 2003 Aug;74(2):179-85
12885934
Pain. 2013 Jan;154(1):160-174
23199705
J Comp Neurol. 2013 Aug 1;521(11):2399-415
23630038
J Basic Clin Physiol Pharmacol. 2016 May 1;27(3):253-65
26565550
Brain Behav Immun. 2011 Aug;25(6):1242-8
21473912
Br J Pharmacol. 2008 Jan;153(2):319-34
17994113
Curr Rheumatol Rep. 2006 Aug;8(4):260-6
16839504
Ocul Immunol Inflamm. 2010 Dec;18(6):488-92
21091058
Invest Ophthalmol Vis Sci. 2015 May;56(5):3304-13
26024113
Pain. 2002 Oct;99(3):547-556
12406531
J Leukoc Biol. 2003 Aug;74(2):172-8
12885933
J Pharmacol Exp Ther. 2011 Dec;339(3):757-67
21885619
Br J Pharmacol. 2013 Jun;169(4):834-43
23461720
Front Neuroanat. 2014 Dec 15;8:150
25565975
Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2264-71
12091426
Invest Ophthalmol Vis Sci. 2005 Jun;46(6):1988-92
15914613
Brain. 2003 Oct;126(Pt 10):2191-202
12876144
DNA Cell Biol. 2002 May-Jun;21(5-6):453-9
12167248
J Comp Neurol. 2010 Sep 15;518(18):3848-66
20653038
Invest Ophthalmol Vis Sci. 1985 Feb;26(2):220-5
3882607
Surv Ophthalmol. 2014 May-Jun;59(3):263-85
24461367
Expert Opin Emerg Drugs. 2011 Jun;16(2):309-22
21210752
J Neuroimmunol. 1998 Jun 15;86(2):171-81
9663563
Exp Eye Res. 2010 Sep;91(3):462-71
20619260
Ocul Surf. 2012 Jan;10(1):2-14
22330055
Br J Ophthalmol. 1996 Sep;80(9):844-8
8962842
Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8079-90
24255040
Arch Ophthalmol. 1982 Feb;100(2):265-7
6279061
Curr Opin Ophthalmol. 2016 Mar;27(2):146-50
26840343
Eur J Neurosci. 2000 Mar;12(3):1123-7
10762343
Br J Pharmacol. 2014 Mar;171(6):1448-61
24308861
Immunobiology. 2010 Sep-Oct;215(9-10):685-91
20573418
Ocul Surf. 2009 Jan;7(1):28-40
19214350
Neural Plast. 2016;2016:8373020
26881135
Br J Pharmacol. 2010 Jun;160(3):627-42
20590567
Prim Care. 2015 Sep;42(3):305-23
26319340
Invest Ophthalmol Vis Sci. 1981 Nov;21(5):759-65
6170602
Brain Res Mol Brain Res. 1998 Jul 15;58(1-2):240-5
9685662
Neural Plast. 2016;2016:9364091
26881140
Eye (Lond). 2009 Oct;23(10):1885-9
19136922
Br J Ophthalmol. 2016 Jan;100(1):128-34
25943558
Neuroscience. 2012 Jan 27;202:117-30
22142900
Arch Ophthalmol. 1983 Apr;101(4):591-3
6301412