Rarily reduced IOP within a welltolerated manner in most patients, 5 lo Inhibitors Related Products whereas 40 mg of CBD, a nonpsychotropic pCB, developed a transient raise of IOP [98]. In this context, the use of animal models pretreated with all the CB1 antagonist SR141716A allowed to demonstrate that THC as well as other pCBs can reduced IOP by straight activating ocular CB1 [99], and also by modulating production and drainage of aqueous humor [99, 100]. Nonetheless, independent studies have shown that Narachidonoylglycine (NAGly) and abnormal cannabidiol (AbnCBD), two agonists of GPR18 (a recently deorphanized G proteincoupled receptor connected to eCBbinding targets), are capable to reduce IOP inside a murine model of disease [101]. A lot of additional preclinical and clinical studies have interrogated the effects of THC and CBD on IOP modulation, establishing valuable effects in individuals with glaucoma even though it’s just a relief of symptoms and, in addition, tolerance, brief duration of these compounds too as peripheral and CNS sideeffects didn’t allow their use in ophthalmic clinic [98, 102107]. Extra recently, scientific interest towards these compounds has been focused on their neuroprotective action that outcomes inside a higher longterm efficacy in treating glaucoma and retinal neurodegenerative ailments. In this context, diverse animal models of ocular diseases have represented appropriate tools to dissect the mechanisms by which pCBs and/or eCBs can exert neuroprotective effects: NMDAinduced retinal cellFig. (1). Inside the eye. Schematic representation of the human eye with an overview of ECS distribution. AEA is manly synthesized by NAPEPLD, whereas DAGL could be the most significant enzyme for the biosynthesis of 2AG. AEA and 2AG signalling pathways are terminated by enzymatic hydrolysis, mediated primarily by the serine hydrolases FAAH and MAGL, respectively. Within the crosssection, the presence of ECS element in different layers with the retina is shown. Abbreviations: AEA, anandamide; 2AG, 2arachidonoylglycerol; NAPEPLD, Narachidonoylphosphatidylethanolaminespecific phospholipase D; DAGL, diacylglycerol lipase; FAAH; fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; CBR, cannabinoid receptors; GPR55, G proteincoupled receptor 55; TRPV1, transient receptor prospective vanilloid variety 1; GLC, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; IS/OS photoreceptor layer; RPE, retinal pigment epithelium.962 Present Neuropharmacology, 2018, Vol. 16, No.Rapino et al.degeneration, AMPA (amino3hydroxy5methyl4isoxazolepropionic acid)induced or lightinduced transient ischemia, 5-HT2C Receptors Inhibitors Related Products IOPreperfusion (glaucoma) along with the streptozotocin (STZ)induced diabetic retinopathy [35, 38, 39, 41, 43, 105, 108110]. Incidentally, it needs to be noted that an excessive extracellular glutamate stimulates NMDA receptors involved in retinal neuronal cell death, an event which is common to glaucoma, retinal ischemia, and diabetic retinopathy. As an example, in a NMDA excitotoxic rat model, THC and CBD had been identified to defend the retina inside a CB1/CB2independent manner, by decreasing peroyxnitrite levels and oxidative stressrelated substances in neurons of the INL and GCL [108]. Regularly, independent studies underlined the antioxidant capacity of THC (and also other pCBs) as a essential function to supply retinal neuroprotection (for any complete critique see [44]). In DR, retinal vascular dysfunction is associated to enhanced production of inflammatory mediators, su.
