A cannabinoid ligand, anandamide, exacerbates endotoxin-induced uveitis in rabbits

J Ocul Pharmacol Ther. 2011 Dec;27(6):545-52. doi: 10.1089/jop.2011.0049. Epub 2011 Aug 17.


Purpose: This study aimed to investigate the effects of anandamide or arachidonylethanolamide (AEA), an endogenous cannabinoid receptor agonist, on intraocular inflammation in an endotoxin-induced uveitis (EIU) model in rabbits.

Methods: Forty New Zealand albino male rabbits were used (5 groups, 8 animals in each). After establishment of sufficient anesthesia, animals were taken under surgery for intravitreal injections. A maximum amount of 50 μL of solution was injected into the central vitreous with a 30-gauge needle. In the control group, sterile saline was injected into the right eyes of the animals. Likewise, AEA (10(-5) M) in the second group, lipopolysaccharide (LPS; 100 ng) in the third group, and AEA (10(-5) M) and LPS (100 ng) in the fourth group were administered. Fifth group received 0.1 mL subtenon injection of AM251 (10(-5) M), a CB(1)-receptor antagonist, 30 min prior to intravitreal LPS (100 ng) and AEA (10(-5) M) injection. At 24 h after the surgical intervention, clinical evaluation was performed and animals were then euthanized with 100 mg/kg intravenous pentobarbital injections. Immediately after the induction of pentobarbital anesthesia, the anterior chamber of the eyes was quickly punctured using a 30-gauge needle to drain aqueous humor (AH) and obtained specimens were used for cell count, protein measurement, and microbiological contamination tests. After AH collection, enucleation was performed and enucleated material was kept for the pathological evaluation.

Results: AEA caused an overall worsening of EIU in studied eyes. It significantly increased the detrimental effects of endotoxin, as assessed by clinical investigation of ocular inflammation, AH leukocyte content, and AH protein concentrations. CB(1)-receptor antagonist AM251 administration reversed some components of this AEA-induced exacerbation to significant extents.

Conclusion: AEA exacerbated EIU in rabbit eyes. AM251 has been found beneficial to prevent AEA's aggravating impact on EIU. As AEA is a treatment choice for lowering intraocular pressure in ophthalmology practice, concurrent use of CB(1)-receptor antagonists may be a questionable strategy in cases of secondary glaucoma, to avoid aggravation of the present inflammation.

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology*
  • Cannabinoid Receptor Agonists
  • Disease Models, Animal
  • Drug Synergism
  • Endocannabinoids
  • Intravitreal Injections
  • Leukocyte Count
  • Lipopolysaccharides / toxicity*
  • Male
  • Neutrophil Infiltration / drug effects
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / pharmacology*
  • Pyrazoles / pharmacology
  • Rabbits
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Severity of Illness Index
  • Uveitis / chemically induced*
  • Uveitis / immunology
  • Uveitis / pathology


  • Arachidonic Acids
  • Cannabinoid Receptor Agonists
  • Endocannabinoids
  • Lipopolysaccharides
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • lipopolysaccharide, Escherichia coli O111 B4
  • AM 251
  • anandamide