Abstract
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.
Highlights
The ocular effects of cannabinoids have been studied extensively in animals and humans over the last few decades
Components of this system, including endocannabinoid ligands that act at two cloned cannabinoid receptors, cannabinoid 1 receptor (CB1R) and cannabinoid 2 receptor (CB2R), and cognate enzymes involved in endocannabinoid biosynthesis and degradation, are present throughout ocular tissues in all species studied to date, including humans and non-human primates (Porcella et al, 1998; Straiker A. et al, 1999; Straiker A.J. et al, 1999; Porcella et al, 2000; Hu et al, 2010; Bouskila et al, 2012, 2013; Cécyre et al, 2013, 2014)
Despite evidence for reducing intraocular pressure (IOP) and potential neuroprotective benefits, the medical community has not embraced the use of cannabinoids as a clinical treatment for glaucoma (Järvinen et al, 2002; Buys and Rafuse, 2010; Novack, 2016). This was documented by the Canadian Ophthalmological Society in a full policy statement released in 2010 (Buys and Rafuse, 2010) and by the American Academy of Ophthalmology in Schwab et al (2014). This is largely because the actions of cannabinoids that act at CB1R in humans and experimental vertebrate animals produce transient alterations in IOP, are subject to tachyphylaxis, and can have both peripheral and central nervous system (CNS) side-effects (Corchero et al, 1999; Chiou et al, 2013)
Summary
The ocular effects of cannabinoids have been studied extensively in animals and humans over the last few decades These compounds generate a number of actions in the eye including: ocular hypotension and hyperemia, as well as modulation of visual function (reviewed in Yazulla, 2008; Cairns et al, 2016a; Kokona et al, 2016). This was documented by the Canadian Ophthalmological Society in a full policy statement released in 2010 (Buys and Rafuse, 2010) and by the American Academy of Ophthalmology in Schwab et al (2014) This is largely because the actions of cannabinoids that act at CB1R in humans and experimental vertebrate animals produce transient alterations in IOP, are subject to tachyphylaxis, and can have both peripheral and CNS side-effects (Corchero et al, 1999; Chiou et al, 2013). The potential of targeting CB1Rs in corneal neuropathic pain is discussed, together with considerations for future research and possible limitations in the use of cannabinoids to treat ocular disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
