Epler and Frank 1971; Flom et al., 1975; Purnell and Gregg, 1975; Cooler and Gregg

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 retinopathy Diabetic retinopathy and 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 both genetic (knockouts) and pharmacological (antagonists) blockade of TRPV1 accelerate RGC degeneration upon exposure to BGC20-761 Purity 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 most likely mediated by Ca2 currents, due to the fact activation of TRPV1 in RGCs increases intracellular Ca2 in isolated RGCs [124, 126]. Along with promoting RGC excitability for the duration of retinal strain, TRPV1 seems to mediate the release of neuroprotective cytokines, for example interleukin (IL) 6, from glial cells [124]. Instead, 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 identified to protect retinal neurons in vivo from injury induced by intravitreal NMDA in rats [127]. Certainly, treatment using the TRPV1 antagonist capsazepine just about totally erased the protective impact in the TRPV1 agonist capsaicin inside the very same model [127]. Other studies 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], in spite of various studies showing that these receptors possess a protective role against this sort of damage [110, 128130]. Almost certainly, such a discrepancy depends upon the distinctive A1 pi4k Inhibitors Related Products models made use of (AMPA toxicity, ischemia/reperfusion and acute ischemia). Inside a cellular model of AMD the expression of CB1 is upregulated and its pharmacological blockade and/or inhibition of CB1 with compact interfering RNA (siRNA) can ameliorate H2O2induced retinal oxidative stress and production of superoxide dismutase (SOD), therefore preventing RPE cell death by means of PI3K/Akt signaling pathway [131]. Inside the pathogenesis of AMD and in other retinal ailments, also photoreceptors play a pivotal part, simply because they represent the primary actors in phototransduction. Lightdamaged animal models happen to be extensively utilized to investigate the mechanisms of neuroretinal dysfunction in numerous ocular illnesses, like human AMD [132, 133]. In line with this, our group offered the initial proof that bright continuous light (BCL) selectively affects ECS gene and protein expression within the albino rat retina, where only CB1 and CB2 levels have been improved [41]. Similarly, accumulated evidence.