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.,Source 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 Adenosine Receptor Inhibitors MedChemExpress 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 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]. Furthermore, 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 likely mediated by Ca2 currents, due to the fact activation of TRPV1 in RGCs increases intracellular Ca2 in isolated RGCs [124, 126]. As well as promoting RGC excitability in the course of retinal tension, TRPV1 appears to mediate the release of neuroprotective cytokines, for instance interleukin (IL) six, from glial cells [124]. Alternatively, 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 identified to protect retinal neurons in vivo from injury induced by intravitreal NMDA in rats [127]. Certainly, therapy with all the TRPV1 antagonist capsazepine just about absolutely erased the protective impact of the TRPV1 agonist capsaicin inside the exact same model [127]. Other research investigated the involvement of eCBbinding receptors in cell death induced by Aldehyde Dehydrogenase (ALDH) Inhibitors products 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 in the early stages of ischemia [39], despite quite a few research displaying that these receptors have a protective part against this sort of harm [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 tiny interfering RNA (siRNA) can ameliorate H2O2induced retinal oxidative pressure and production of superoxide dismutase (SOD), hence stopping RPE cell death through PI3K/Akt signaling pathway [131]. Inside the pathogenesis of AMD and in other retinal ailments, also photoreceptors play a pivotal part, because they represent the principle actors in phototransduction. Lightdamaged animal models happen to be broadly utilized to investigate the mechanisms of neuroretinal dysfunction in numerous ocular illnesses, which includes human AMD [132, 133]. In line with this, our group supplied the initial evidence 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 improved [41]. Similarly, accumulated evidence.