Department of Ophthalmology, Gazi University School of Medicine, Besevler, Ankara, Turkey.
J Ocul Pharmacol Ther. 2011 Dec;27(6):545-52. doi: 10.1089/jop.2011.0049. Epub 2011 Aug 17.
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.
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.
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.
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.
本研究旨在探讨内源性大麻素受体激动剂花生四烯酰乙醇胺（AEA）对内毒素诱导的兔葡萄膜炎（EIU）模型眼内炎症的影响。
40 只新西兰雄性白兔（5 组，每组 8 只）用于本研究。充分麻醉后，对动物进行手术行玻璃体内注射。用 30 号针头向中央玻璃体腔内注射最多 50μL 溶液。在对照组中，向动物右眼注射无菌生理盐水。同样，第二组给予 AEA（10（-5）M），第三组给予脂多糖（LPS；100ng），第四组给予 AEA（10（-5）M）和 LPS（100ng）。第五组在玻璃体内注射 LPS（100ng）和 AEA（10（-5）M）前 30 分钟，接受 0.1mL 亚妥因 AM251（10（-5）M）注射，AM251 是一种 CB1 受体拮抗剂。手术干预后 24 小时进行临床评估，然后用 100mg/kg 静脉戊巴比妥钠注射处死动物。在诱导戊巴比妥钠麻醉后，用 30 号针头快速刺穿眼前房以排出房水（AH），收集的标本用于细胞计数、蛋白质测量和微生物污染测试。AH 采集后，行眼球摘除术，将眼球摘除标本用于病理评估。
AEA 导致研究眼 EIU 总体恶化。它通过临床评估眼部炎症、房水中白细胞含量和房水蛋白浓度，显著增加了内毒素的有害作用。CB1 受体拮抗剂 AM251 的给药在很大程度上逆转了这种 AEA 诱导的加剧作用的某些成分。
AEA 加剧了兔眼 EIU。AM251 已被发现有助于预防 AEA 对 EIU 的加重影响。由于 AEA 是眼科实践中降低眼内压的治疗选择，在继发性青光眼的情况下，同时使用 CB1 受体拮抗剂可能是一个有问题的策略，以避免现有炎症的恶化。
