Nd binding research [62, 64, 6669]. Incidentally, CB1 was also found in brain places like thalamus and cortex, recognized to influence visual output [7072], as well as in trabecular meshwork, Schlemm’s canal and ciliary physique, where also CB2 is expressed [66, 7375]. A lot of research demonstrated the presence of TRPV1 as well as other TRP subunits at mRNA and protein level in mammalian and nonmammalian retina, and within a variety of neuronal and glial cells of this location; however, outcomes remained controversial, possibly due to the use of different antibodies and staining protocols [35, 63, 7681]. Interestingly, TRPV1 may possibly play a major functional function within the inner retina, considering the fact 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, Mitoguazone Apoptosis suggesting a function function in scotopic vision [65, 69]. Indeed, retinal function has been assessed by many flash electroretinogram (ERG) measurements in the presence of selective antagonists of CB1 and CB2, suggesting the involvement of eCB signaling inside the modulation of retinal response. ECS can also be involved in neurotransmission inside the retina. Indeed, by acting on ionic currents and electrical potentials, it might modulate the release of many Maleimide Epigenetic Reader Domain neurotransmitters for instance dopamine, noradrenaline, GABA and glutamate, that manage synaptic activity in retinal ganglion cells and consequently modulate visual response [8287]. Additionally, AEA, 2AG and their congener Npalmitoylethanolamine (PEA) happen to be measured by gas chromatographymass spectrometry in human ocular tissues, demonstrating an general greater content of 2AG when compared with AEA in human retina, and a content adjust upon retinal degenerative diseases [75, 88, 89]. 2AG and AEA levels are high in retina with DR and agerelated macular degeneration [89], whereas glaucoma patients have decreased levels of 2Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative DiseasesCurrent Neuropharmacology, 2018, Vol. 16, No.AG and PEA without having modifications in AEA inside the same sufferers [88]. In addition, FAAH expression is remarkable in various layers of retina, from OPL to GCL (ganglion cell layer) in rats, zebrafishes, gold fishes, monkeys and humans [64, 90, 91], and FAAH activity is often measured in the exact same species and especially in mice and rats, exactly where it’s greater in rods, bipolar cells, horizontal cells, amacrine cells, Muller cells and ganglion cells. Additionally, NAPEPLD was identified inside the retina of rodents as well as other mammals [90], and lately the presence of DAGL and MAGL mRNAs was documented in rat retina [41], extending preceding data on their localization for the duration of postnatal development [62]. Extra specifically, DAGL was identified to be expressed within the postsynaptic terminals of cone bipolar cells, whereas MAGL in 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 initial evidence for any constructive part of pCBs in retina protection dates back for the `70s, when smoking marijuana was discovered to reduced IOP within a smaller variety of subjects [93]. Then, numerous experimental findings demonstrated that oral or intravenous administration of THC to human subjects with glaucoma reduces IOP, though with improvement of tolerance and important education of systemic blood pressure and tachycardia [9497]. As an alternative, single sublingual administration of THC tempo.