Alpha-2 Adrenergic Receptor Agonists are Neuroprotective in Experimental Models of Glaucoma

溴莫尼定 神经保护 医学 兴奋剂 视网膜 药理学 青光眼 视神经 眼科 视网膜神经节细胞 麻醉 受体 内科学 神经科学 生物
作者
L. A. Wheeler,Elizabeth WoldeMussie
出处
期刊:European Journal of Ophthalmology [SAGE Publishing]
卷期号:11 (2_suppl): 30-35 被引量:64
标识
DOI:10.1177/112067210101102s03
摘要

Purpose The glaucomas are characterized by chronic progressive ganglion cell loss over many years. A drug with neuroprotective activity should increase the resistance of retinal ganglion cells (RGC) to chronic stress or injury and therefore enhance survival. Brimonidine is a highly selective and potent alpha-2 adrenergic receptor agonist, which lowers intra-ocular pressure (IOP) and is neuroprotective. Immunohistochemistry data have shown that the specific receptor targets, the alpha-2 receptors, are located in the inner retina. Methods Brimonidine 0.1 mg/kg given intraperitoneally promoted RGC survival compared with vehicle using the optic nerve crush model even when administered up to 24 hours before injury. Using the chronic ocular hypertensive rat model, brimonidine 1 mg/kg/day (with osmotic pump) significantly prevented the loss of RGCs when compared with vehicle or timolol. This ability was due to the neuroprotective action of brimonidine, since it did not affect IOP. In addition, brimonidine 0.1 mg/day reached concentrations in the retina of Sprague-Dawley rats within 30 minutes of injection, which was sufficient to activate the alpha-2 receptor (≥ 2 nM) and maintained these concentrations for 6 hours. Conclusions Having demonstrated that: a. the specific receptor target of brimonidine is located in the retina, which is important for optic neuroprotection, b. the agent shows neuroprotective ability in animal models, c. pharmacological concentrations of the drug can be reached in the retina, clinical trial has been initiated to determine whether brimonidine is neuroprotective in patients with nonarteritic ischaemic optic neuropathy.
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