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 Diazo Biotin-PEG3-DBCO Autophagy glaucomaNeuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative DiseasesCurrent Neuropharmacology, 2018, Vol. 16, No.ported that TRPV1 plays a significant role 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) 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, as a result supporting enhanced excitability. Such an enhancement is probably mediated by Ca2 currents, considering the fact that activation of TRPV1 in RGCs increases intracellular Ca2 in isolated RGCs [124, 126]. As well as promoting RGC excitability in the course of retinal anxiety, TRPV1 seems to mediate the release of neuroprotective cytokines, for instance interleukin (IL) six, from glial cells [124]. Instead, in adult retinal explants each genetic and pharmacological blockade of TRPV1 enhanced RGC survival upon exposure to elevated hydrostatic pressure, as did chelation of extracellular Ca2 [124]. Activation of TRPV1 was discovered to defend retinal neurons in vivo from injury induced by intravitreal NMDA in rats [127]. Certainly, remedy using the TRPV1 antagonist capsazepine pretty much entirely erased the protective effect of your TRPV1 agonist capsaicin within the similar model [127]. Other research investigated the involvement of eCBbinding receptors in cell death induced by Adrenergic Related Compounds Inhibitors medchemexpress 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], in spite of quite a few research showing that these receptors have a protective function against this sort of damage [110, 128130]. Most likely, such a discrepancy depends upon the distinct models applied (AMPA toxicity, ischemia/reperfusion and acute ischemia). In a cellular model of AMD the expression of CB1 is upregulated and its pharmacological blockade and/or inhibition of CB1 with tiny interfering RNA (siRNA) can ameliorate H2O2induced retinal oxidative tension and production of superoxide dismutase (SOD), therefore stopping RPE cell death by way of PI3K/Akt signaling pathway [131]. In the pathogenesis of AMD and in other retinal illnesses, also photoreceptors play a pivotal part, since they represent the primary actors in phototransduction. Lightdamaged animal models happen to be extensively used to investigate the mechanisms of neuroretinal dysfunction in a number of ocular diseases, including human AMD [132, 133]. In line with this, our group provided the initial proof that bright continuous light (BCL) selectively impacts ECS gene and protein expression inside the albino rat retina, exactly where only CB1 and CB2 levels were increased [41]. Similarly, accumulated evidence.