Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases

Abstract

Background: Emerging neuroprotective strategies are being explored to preserve the retina from degeneration, that occurs in eye pathologies like glaucoma, diabetic retinopathy, age-related macular degeneration, and retinitis pigmentosa. Incidentally, neuroprotection of retina is a defending mechanism designed to prevent or delay neuronal cell death, and to maintain neural function following an initial insult, thus avoiding loss of vision.

Methods: Numerous studies have investigated potential neuroprotective properties of plant-derived phytocannabinoids, as well as of their endogenous counterparts collectively termed endocannabinoids (eCBs), in several degenerative diseases of the retina. eCBs are a group of neuromodulators that, mainly by activating G protein-coupled type-1 and type-2 cannabinoid (CB1 and CB2) receptors, trigger multiple signal transduction cascades that modulate central and peripheral cell functions. A fine balance between biosynthetic and degrading enzymes that control the right concentration of eCBs has been shown to provide neuroprotection in traumatic, ischemic, inflammatory and neurotoxic damage of the brain.

Results: Since the existence of eCBs and their binding receptors was documented in the retina of numerous species (from fishes to primates), their involvement in the visual processing has been demonstrated, more recently with a focus on retinal neurodegeneration and neuroprotection.

Conclusion: The aim of this review is to present a modern view of the endocannabinoid system, in order to discuss in a better perspective available data from preclinical studies on the use of eCBs as new neuroprotective agents, potentially useful to prevent glaucoma and retinal neurodegenerative diseases.

Keywords: Neuroprotection; endocannabinoids; glaucoma; phytocannabinoids; retinal diseases; retinal ganglion cells..

Fig. (1)

Inside the eye. Schematic representation of the human eye with an overview of ECS distribution. AEA is manly synthesized by NAPE-PLD, whereas DAGL is the most important enzyme for the biosynthesis of 2-AG. AEA and 2-AG signalling pathways are terminated by enzymatic hydrolysis, mediated primarily by the serine hydrolases FAAH and MAGL, respectively. In the cross-section, the presence of ECS element in different layers of the retina is shown. Abbreviations: AEA, anandamide; 2-AG, 2-arachidonoylglycerol; NAPE-PLD, N-arachidonoylphosphatidylethanolamine-specific phospholipase D; DAGL, diacylglycerol lipase; FAAH; fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; CBR, cannabinoid receptors; GPR55, G protein-coupled receptor 55; TRPV1, transient receptor potential vanilloid type 1; GLC, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; IS/OS photoreceptor layer; RPE, retinal pigment epithelium.