Epler and Frank 1971; Flom et al., 1975; Purnell and Gregg, 1975; Cooler and Gregg 1977; Flach et al., 2002; Tomida et al., 2006 Colasanti 1990 Caldwell et al., 2013 Fischer et al., 2013 Hingorani et al., 2012 ElRemessy et al., 2003 Crandall et al., 2007 ElRemessy et al., 2006 Araujoa et al.,Supply of ModelHumanEyeIOP reductionGlaucomaCat, Rat Mouse Dog Rabbit Rat Rat ChickEye Anterior Eye Eye Cornea Retinal Ganglion Cells Retinal Neuronal Cells Retinal SectionIOP reduction IOP reduction IOP reduction IOP reduction Cell protection Cell protection Cell protectionGlaucoma Glaucoma Glaucoma Glaucoma Glaucoma Diabetic retinopathy Diabetic retinopathy and glaucomaNeuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative DiseasesCurrent Neuropharmacology, 2018, Vol. 16, No.ported that TRPV1 plays a major part as a mediator of RGC function and survival [124126]. In line with this, in an inducible mouse model of glaucoma each genetic (knockouts) and pharmacological (antagonists) 15 pgdh Inhibitors MedChemExpress blockade of TRPV1 accelerate RGC degeneration upon exposure to elevated IOP [125]. In addition, in vivo TRPV1 expression increases in monkey and human RGCs in response to elevated IOP, therefore supporting enhanced excitability. Such an enhancement is probably mediated by Ca2 currents, considering that activation of TRPV1 in RGCs increases intracellular Ca2 in isolated RGCs [124, 126]. Along with advertising RGC excitability through retinal anxiety, TRPV1 appears to mediate the release of neuroprotective cytokines, like interleukin (IL) six, from glial cells [124]. As an alternative, in adult retinal explants each genetic and pharmacological blockade of TRPV1 improved RGC survival upon exposure to elevated hydrostatic pressure, as did chelation of extracellular Ca2 [124]. Activation of TRPV1 was found to safeguard retinal neurons in vivo from injury induced by intravitreal NMDA in rats [127]. Indeed, treatment together with the TRPV1 antagonist capsazepine practically entirely erased the protective effect with the TRPV1 agonist capsaicin within the same model [127]. Other research investigated the involvement of eCBbinding receptors in cell death induced by ischemia in an avascular (chick) retina model exactly where oxygen and glucose deprivation (OGD) was induced. They failed to demonstrate an involvement of CB1 and CB2 in driving cell death at the early stages of ischemia [39], despite a number of studies displaying that these receptors have a protective role against this type of damage [110, 128130]. Most likely, such a discrepancy will depend on the various models utilised (AMPA toxicity, ischemia/reperfusion and acute ischemia). Within a cellular model of AMD the expression of CB1 is upregulated and its pharmacological blockade and/or inhibition of CB1 with little interfering RNA (siRNA) can ameliorate H2O2induced retinal oxidative stress and production of superoxide dismutase (SOD), as a result stopping RPE cell death by way of PI3K/Akt signaling pathway [131]. Inside the pathogenesis of AMD and in other retinal ailments, also photoreceptors play a pivotal part, since they represent the primary actors in phototransduction. Lightdamaged animal models happen to be widely employed to investigate the mechanisms of neuroretinal dysfunction in numerous ocular ailments, which includes human AMD [132, 133]. In line with this, our group offered the very first Disodium 5′-inosinate custom synthesis evidence that bright continuous light (BCL) selectively affects ECS gene and protein expression inside the albino rat retina, exactly where only CB1 and CB2 levels had been increased [41]. Similarly, accumulated evidence.