Nd binding research [62, 64, 6669]. Incidentally, CB1 was also identified in brain areas like thalamus and cortex, known to influence visual output [7072], also as in trabecular meshwork, Schlemm’s canal and ciliary physique, where also CB2 is expressed [66, 7375]. Numerous studies demonstrated the presence of TRPV1 along with other TRP subunits at mRNA and protein level in mammalian and nonmammalian retina, and inside a number of neuronal and glial cells of this location; yet, results remained controversial, possibly due to the use of distinct antibodies and staining protocols [35, 63, 7681]. Interestingly, TRPV1 could play a significant functional function within the inner retina, due to the fact it was not detected in photoreceptors and bipolar cells [63]. As for GPR55, its presence has been documented only inside 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 several flash electroretinogram (ERG) measurements in the presence of selective antagonists of CB1 and CB2, suggesting the involvement of eCB signaling within the modulation of retinal response. ECS can also be involved in neurotransmission within the retina. Certainly, by acting on ionic currents and electrical potentials, it might modulate the release of many neurotransmitters such as dopamine, noradrenaline, GABA and 2-Iminobiotin Inhibitor glutamate, that manage synaptic activity in retinal ganglion cells and consequently modulate visual response [8287]. Also, AEA, 2AG and their congener Npalmitoylethanolamine (PEA) happen to be measured by gas chromatographymass spectrometry in human ocular tissues, demonstrating an general greater content material of 2AG in comparison to AEA in human retina, in addition to a content material transform 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 decreased levels of 2Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative DiseasesCurrent Neuropharmacology, 2018, Vol. 16, No.AG and PEA devoid of alterations in AEA inside the same Aldehyde Dehydrogenase (ALDH) Inhibitors Reagents individuals [88]. Moreover, FAAH expression is exceptional in different layers of retina, from OPL to GCL (ganglion cell layer) in rats, zebrafishes, gold fishes, monkeys and humans [64, 90, 91], and FAAH activity might be measured inside the same species and particularly in mice and rats, where it can be greater in rods, bipolar cells, horizontal cells, amacrine cells, Muller cells and ganglion cells. In addition, NAPEPLD was identified within 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 earlier information on their localization through postnatal development [62]. A lot more especially, DAGL was identified to become expressed within 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 first proof to get a constructive part of pCBs in retina protection dates back towards the `70s, when smoking marijuana was located to lower IOP within a modest quantity of subjects [93]. Then, numerous experimental findings demonstrated that oral or intravenous administration of THC to human subjects with glaucoma reduces IOP, even though with development of tolerance and substantial education of systemic blood stress and tachycardia [9497]. Rather, single sublingual administration of THC tempo.