Nd binding studies [62, 64, 6669]. Incidentally, CB1 was also discovered in brain locations like

Nd binding studies [62, 64, 6669]. Incidentally, CB1 was also discovered in brain locations like thalamus and cortex, recognized to influence visual output [7072], as well as in trabecular meshwork, Schlemm’s canal and ciliary body, where also CB2 is expressed [66, 7375]. A lot of studies demonstrated the presence of TRPV1 and other TRP subunits at mRNA and protein level in mammalian and nonmammalian retina, and inside a number of neuronal and glial cells of this region; yet, final results remained controversial, possibly because of the use of distinctive antibodies and staining protocols [35, 63, 7681]. Interestingly, TRPV1 may perhaps play a major functional role inside the inner retina, given that it was not detected in photoreceptors and bipolar cells [63]. As for GPR55, its presence has been documented only in the inner segments of rod photoreceptors of monkey retina, suggesting a function function in scotopic vision [65, 69]. Certainly, retinal function has been assessed by numerous flash electroretinogram (ERG) measurements within the presence of selective antagonists of CB1 and CB2, suggesting the involvement of eCB signaling in the modulation of retinal response. ECS is also involved in neurotransmission inside the retina. Certainly, by acting on ionic currents and electrical potentials, it may modulate the Adenosine A2A Receptors Inhibitors Reagents release of many neurotransmitters such as dopamine, noradrenaline, GABA and glutamate, that manage synaptic activity in retinal ganglion cells and consequently modulate visual response [8287]. In addition, AEA, 2AG and their congener Npalmitoylethanolamine (PEA) happen to be measured by gas chromatographymass spectrometry in human ocular tissues, demonstrating an all round greater content of 2AG in comparison to AEA in human retina, plus a content material change upon retinal degenerative ailments [75, 88, 89]. 2AG and AEA levels are higher in retina with DR and agerelated macular degeneration [89], whereas glaucoma patients have lowered levels of 2Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative DiseasesCurrent Neuropharmacology, 2018, Vol. 16, No.AG and PEA with out adjustments in AEA within the similar sufferers [88]. Furthermore, FAAH expression is outstanding in various layers of retina, from OPL to GCL (ganglion cell layer) in rats, zebrafishes, gold fishes, A11466 5 cathepsin Inhibitors medchemexpress monkeys and humans [64, 90, 91], and FAAH activity is often measured in the very same species and specifically in mice and rats, where it really is higher in rods, bipolar cells, horizontal cells, amacrine cells, Muller cells and ganglion cells. Additionally, NAPEPLD was identified inside the retina of rodents along with other mammals [90], and lately the presence of DAGL and MAGL mRNAs was documented in rat retina [41], extending preceding data on their localization throughout postnatal development [62]. More particularly, DAGL was discovered to become expressed inside the postsynaptic terminals of cone bipolar cells, whereas MAGL inside the IPL and OPL [92]. Localization of ECS elements in retina is schematically depicted in Fig. (1). 4. PHYTOCANNABINOIDS, IOP REDUCTION AND RETINAL PROTECTION The very first evidence for any constructive function of pCBs in retina protection dates back for the `70s, when smoking marijuana was located to reduced IOP within a small variety of subjects [93]. Then, various experimental findings demonstrated that oral or intravenous administration of THC to human subjects with glaucoma reduces IOP, although with development of tolerance and important education of systemic blood pressure and tachycardia [9497]. Rather, single sublingual administration of THC tempo.