Finding of endocannabinoids in human eye tissues: Implications for glaucoma

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Abstract

Cannabinoid CB1 receptors are involved in ocular physiology and may regulate intraocular pressure (IOP). However, endocannabinoid levels in human ocular tissues of cornea, iris, ciliary body, retina, and choroid from normal and glaucomatous donors have not been investigated. Anandamide (N-arachidonoylethanolamine; AEA), 2-arachidonoylglycerol (2-AG), and the anandamide congener, palmitoylethanolamide (PEA), were detected in all the human tissues examined. In eyes from patients with glaucoma, significantly decreased 2-AG and PEA levels were detected in the ciliary body, an important tissue in the regulation of IOP. The findings suggest that these endogenous compounds may have a role in this disease, particularly with respect to regulation of IOP.

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Materials and methods

Human eyes. Normal eyes (n = 12) or glaucomatous eyes (n = 12) of donors were obtained from the National Disease Research Interchange (Philadelphia, PA, USA) and the Central Florida Lions Eye and Tissue Bank (Tampa, FL, USA). The organ banks obtained informed consent from all donors or their family members. The mean donor age was 70.5 ± 2.6 years (range 49–90) for normal eyes and 76.0 ± 3.5 years (range 56–91) for glaucomatous eyes. The eyes were enucleated 2–10 h after death, stored in

Comparison of endocannabinoid levels in the different eye tissues

In human normal and glaucomatous eyes, 2-AG, PEA, and AEA were detected in all the tissues examined. The levels of individual substances varied between the ocular tissues and ranged as follows: 2-AG (range 62–1393 pmol/g tissue; Fig. 1), PEA (range 95–637 pmol/g tissue; Fig. 2), and AEA (range 24–178 pmol/g tissue; Fig. 3). 2-AG levels were higher in the human normal retina (1393 ± 213 pmol/g), ciliary body (503 ± 92 pmol/g), and choroid (493 ± 204 pmol/g) compared to the iris (118 ± 21 pmol/g) and cornea (65 ±

Discussion

Glaucoma is a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and their axons, with resultant visual field defects and loss of vision [23], [24], [25], [26]. This ocular disease is the second leading cause of blindness worldwide and patients are usually asymptomatic until late in the course of the disease [23], [24], [25]. Elevated IOP and large diurnal IOP fluctuations are well-understood risk factors for the development of glaucoma and

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    Abbreviations: AEA, anandamide, N-arachidonoylethanolamine; 2-AG, 2-arachidonoylglycerol; CB, cannabinoid; FAAH, fatty acid amide hydrolase; IOP, intraocular pressure; LC-APCI-MS, liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry; NAAA, N-acylethanolamine-hydrolyzing acid amidase; NAPE-PLD, N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D; MAGL; monoacylglycerol lipase; PEA, palmitoylethanolamide; POAG, primary open-angle glaucoma; PLC, phospholipase C; PLA2, phospholipase A2; TRPV1, transient receptor potential vanilloid type 1.

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