Opioid Receptor-Activation: Retina Protected from Ischemic Injury
Opioid Receptor-Activation: Retina Protected from Ischemic Injury
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DOI：
10.1167/iovs.08-2907
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Crosson, Craig E.
中科院分区：
文献类型：
--
作者：
Husain, Shahid;Potter, David E.;Crosson, Craig E.
目的.在非眼系统中，阿片受体的激活已被证明可以改善由缺血应激诱导的组织损伤。本研究旨在探讨内源性或外源性激动剂激活阿片受体是否能改善缺血性视网膜损伤。在内源性阿片受体激活是否减少缺血性损伤的研究中，评价了阿片受体拮抗剂纳洛酮（3 mg/kg; IP）对缺血预处理（IPC）诱导的视网膜神经保护作用的影响。采用吗啡（0.01~10mg/kg）预处理大鼠，观察外源性阿片类药物对缺血性视网膜损伤的影响。形态测量和视网膜电图（ERG）分析用于评估视网膜结构和功能的差异。阿片受体亚型的表达通过蛋白质印迹和免疫组织化学分析来评估。在对照动物中，缺血性视网膜损伤后7天，ERG a-和b-波振幅显著降低（分别为23%和41%）。此外，内层视网膜的变性导致整体视网膜厚度减少34%。在缺血性损伤前接受IPC的动物中，ERG波形和视网膜形态得以保留。纳洛酮预处理可逆转IPC诱导的功能性和结构性视网膜保护。在缺血性损伤前24小时用吗啡处理的动物中，ERG波形以剂量依赖性方式（ED 50 = 0.18 mg/kg）被保留，并且这种保护性反应被纳洛酮预处理逆转。免疫组化和Western blot结果显示，视网膜中表达δ-、κ-和μ-阿片受体亚型。这些数据提供了一种（或多种）阿片受体的激活促进视网膜内IPC的发展并且可以减少缺血性视网膜损伤的证据。（Invest Ophthalmol维斯科学。2009; 50：3853 - 3859）DOI：10.1167/iovs.08 - 2907
PURPOSE. In nonocular systems, activation of opioid receptors has been shown to ameliorate tissue damage induced by ischemic stress. The current study was an investigation of whether opioid receptors activated by endogenous or exogenous agonists can ameliorate ischemic retinal injury.METHODS. In an investigation of whether endogenous opioid receptor-activation reduces ischemic injury, the effects of the opioid antagonist naloxone (3 mg/kg; IP) on retinal neuroprotection induced by ischemic preconditioning (IPC) were evaluated. Whether exogenous opioid administration can reduce ischemic retinal injury was determined by pretreating rats with morphine (0.01-10 mg/kg) before injury. Morphometric and electroretinogram (ERG) analyses were used to assess the differences in retinal structure and function. The expression of opioid receptor subtypes was evaluated by Western blot and immunohistochemical analyses.RESULTS. In control animals, 7 days after ischemic retinal injury, ERG a-and b-wave amplitudes were significantly reduced (23% and 41%, respectively). In addition, degeneration of the inner retina resulted in a 34% reduction in overall retina thickness. In animals receiving IPC before ischemic injury, ERG wave forms and retinal morphology were preserved. Pretreatment with naloxone reversed both the functional and structural retinal protection induced by IPC. In animals treated with morphine 24-hours before ischemic injury, ERG waveforms were preserved in a dose-dependent fashion (ED50 = 0.18 mg/kg), and this protective response was reversed by naloxone pretreatment. Immunohistochemical and Western blot data demonstrated that the delta-, kappa-, and mu-opioid receptor subtypes are expressed in the retina.CONCLUSIONS. These data provide evidence that activation of one (or more) opioid receptor(s) facilitates the development of IPC within the retina and can reduce ischemic retina injury. (Invest Ophthalmol Vis Sci. 2009; 50: 3853-3859) DOI: 10.1167/iovs.08-2907